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Reciprocal connections between the thalamus and the cortex are one of the most characteristic features of forebrain organization in mammals. To date, this circuit has been documented only in turtles. However, reptiles, including turtles, have an additional path from the dorsal thalamus to the telencephalon. This terminates in a pallial structure known as the dorsal ventricular ridge. Yet, no reciprocal connection from the dorsal ventricular ridge to thalamic nuclei has been uncovered. Since axons from the thalamus pass through the basal nuclei on route to the dorsal ventricular ridge, the basal nuclei might be a source of reciprocal connections. Accordingly, the location and distribution of neurons after retrograde tracer placement into the dorsal thalamus were examined. Retrogradely labeled neurons in the basal nuclei were indeed found. One possibility to explain this observation is that connections with the dorsal ventricular ridge are present during development but later pruned during embryogenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The thalamus is one of the most important divisions of the forebrain because it serves as the major hub for transmission of information between the brainstem and telencephalon. While many studies have investigated the thalamus in mammals, comparable analyses in reptiles are incomplete. To fill this gap in knowledge, the thalamus was investigated in crocodiles using a variety of morphological techniques. The thalamus consists of two parts: a dorsal and a ventral division. The dorsal thalamus was defined by its projections to the telencephalon, whereas the ventral thalamus lacked this circuit. The complement of nuclei in each part of the thalamus was identified and characterized. Alar and basal components of both the dorsal and ventral thalamus were distinguished. Although some alar-derived nuclei in the dorsal thalamus shared certain features, no grouping could account for all of the known nuclei. However, immunohistochemical observations suggested a subdivision of alar-derived ventral thalamic nuclei. In view of this, a different approach to the organization of the dorsal thalamus should be considered. Development of the dorsal thalamus is suggested to be one way to provide a fresh perspective on its organization., (© 2024 Wiley Periodicals LLC.)

In mammals, the zona incerta is thought to be involved in a number of behaviors: visceral activity, arousal, attention, and posture and locomotion. These diverse and complex features suggested that the zona incerta functions as a global or integrative node. Nevertheless, despite multiple investigations into its anatomy, physiology, and behavior in a variety of mammals, no specific character identifies the zona incerta besides its appearance in fiber-stained material and its relationship to surrounding structures. One such structure is the thalamic reticular nucleus whose caudal pole often contains some intermingled cells of the zona incerta. In crocodilians, the entopeduncular nucleus (ep) abuts the caudal pole of the thalamic reticular nucleus and displays different immunohistochemical properties and soma size when compared with neurons in the thalamic reticular nucleus itself. To determine if neurons in the ep differed from those in the thalamic reticular nucleus in Alligator mississippiensis, the ep was investigated using Golgi methodology. The morphology and soma size of neurons in the ep differed from those in the thalamic reticular nucleus and indicated that these two areas are indeed separate neuronal aggregates. Based on these data and the known relationships of the zona incerta to surrounding structures in mammals, the ep of crocodilians is suggested to be the counterpart of the zona incerta of mammals., (© 2021 Wiley Periodicals LLC.)

Higher-order thalamic nuclei contribute to sensory processing via projections to primary and higher cerebral cortical areas, but it is unknown which of their cortical and subcortical inputs contribute to their distinct output pathways. We used subpopulation specific viral strategies in mice to anatomically and physiologically dissect pathways of the higher-order thalamic nuclei of the somatosensory and visual systems (the posterior medial nucleus and pulvinar). Employing a complementary optogenetics and electrical stimulation strategy, we show that synapses in cortex from higher-order thalamus have functionally divergent properties in primary vs. higher cortical areas. Higher-order thalamic projections onto excitatory targets in S1 and V1 were weakly modulatory, while projections to S2 and higher visual areas were strong drivers of postsynaptic targets. Then, using transsynaptic tracing verified by optogenetics to map inputs to higher-order thalamus, we show that posterior medial nucleus cells projecting to S1 are driven by neurons in layer 5 of S1, S2, and M1 and that pulvinar cells projecting to V1 are driven by neurons in layer 5 of V1 and higher visual areas. Therefore, in both systems, layer 5 of primary and higher cortical areas drives transthalamic feedback modulation of primary sensory cortex through higher-order thalamus. These results highlight conserved organization that may be shared by other thalamocortical circuitry. They also support the hypothesis that direct corticocortical projections in the brain are paralleled by transthalamic pathways, even in the feedback direction, with feedforward transthalamic pathways acting as drivers, while feedback through thalamus is modulatory.

Although corticothalamic neurons (CThNs) represent the largest source of synaptic input to thalamic neurons, their role in regulating thalamocortical interactions remains incompletely understood. CThNs in sensory cortex have historically been divided into two types, those with cell bodies in Layer 6 (L6) that project back to primary sensory thalamic nuclei and those with cell bodies in Layer 5 (L5) that project to higher-order thalamic nuclei and subcortical structures. Recently, diversity among L6 CThNs has increasingly been appreciated. In the rodent somatosensory cortex, two major classes of L6 CThNs have been identified: one projecting to the ventral posterior medial nucleus (VPM-only L6 CThNs) and one projecting to both VPM and the posterior medial nucleus (VPM/POm L6 CThNs). Using rabies-based tracing methods in mice, we asked whether these L6 CThN populations integrate similar synaptic inputs. We found that both types of L6 CThNs received local input from somatosensory cortex and thalamic input from VPM and POm. However, VPM/POm L6 CThNs received significantly more input from a number of additional cortical areas, higher order thalamic nuclei, and subcortical structures. We also found that the two types of L6 CThNs target different functional regions within the thalamic reticular nucleus (TRN). Together, our results indicate that these two types of L6 CThNs represent distinct information streams in the somatosensory cortex and suggest that VPM-only L6 CThNs regulate, via their more restricted circuits, sensory responses related to a cortical column while VPM/POm L6 CThNs, which are integrated into more widespread POm-related circuits, relay contextual information., (© 2021 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.)

The thalamic reticular nucleus (TRN) is a critical structure influencing information transfer to the forebrain. In crocodilians, the TRN shares many features with its mammalian counterpart. One area that has not been explored is how individual neurons in the crocodilian TRN compare with those found in mammals. In mammals, TRN neurons are aligned parallel to the external border of the dorsal thalamus, have their dendrites oriented perpendicular to the fibers in the internal capsule, have fine, filamentous dendritic appendages, are either bipolar or multipolar, and are commonly considered to be a homogeneous morphological population of cells. To investigate the cellular morphology of the TRN complex, a Golgi analysis was undertaken in Alligator mississippiensis. This study examined features that have been used in mammals. In Alligator, the four TRN divisions are the dorsal peduncular nucleus, the perireticular nucleus, the interstitial nucleus, and the neurons in the medial forebrain bundle associated with the interstitial nucleus. In crocodilians, the dorsal peduncular nucleus is homologous to the TRN of mammals. From the 1787 drawn neuron profiles in the traditional three planes of section, the following were concluded. First, neurons in each part of the TRN complex in Alligator were similar in morphology. Second, each part of the TRN complex of Alligator contained a heterogenous population of cells. These variations between the cellular morphology of the dorsal peduncular nucleus of crocodilians and the TRN of mammals are speculated to partly result from differences in forebrain organization., (© 2021 Wiley Periodicals LLC.)

Songbirds learn vocalizations by hearing and practicing songs. As song develops, the tempo becomes faster and more precise. In the songbird brain, discrete nuclei form interconnected myelinated circuits that control song acquisition and production. The myelin sheath increases the speed of action potential propagation by insulating the axons of neurons and by reducing membrane capacitance. As the brain develops, myelin increases in density, but the time course of myelin development across discrete song nuclei has not been systematically studied in a quantitative fashion. We tested the hypothesis that myelination develops differentially across time and song nuclei. We examined myelin development in the brains of the zebra finch (Taeniopygia guttata) from chick at posthatch day (d) 8 to adult (up to 147 d) in five major song nuclei: HVC (proper name), robust nucleus of the arcopallium (RA), Area X, lateral magnocellular nucleus of the anterior nidopallium, and medial portion of the dorsolateral thalamic nucleus (DLM). All of these nuclei showed an increase in the density of myelination during development but at different rates and to different final degrees. Exponential curve fits revealed that DLM showed earlier myelination than other nuclei, and HVC showed the slowest myelination of song nuclei. Together, these data show differential maturation of myelination in different portions of the song system. Such differential maturation would be well placed to play a role in regulating the development of learned song., (© 2020 Wiley Periodicals LLC.)

The nucleus prethalamicus (PTh) receives fibers from the optic tectum and then projects to the dorsal telencephalon in the yellowfin goby Acanthogobius flavimanus. However, it remained unclear whether the PTh is a visual relay nucleus, because the optic tectum receives not only visual but also other sensory modalities. Furthermore, precise telencephalic regions receiving prethalamic input remained unknown in the goby. We therefore investigated the full set of afferent and efferent connections of the PTh by direct tracer injections into the nucleus. Injections into the PTh labeled cells in the optic tectum, ventromedial thalamic nucleus, central and medial parts of the dorsal telencephalon, and caudal lobe of the cerebellum. We found that the somata of most tecto-prethalamic neurons are present in the stratum periventriculare. Their dendrites ascend to reach the major retinorecipient layers of the tectum. The PTh is composed of two subnuclei (medial and lateral) and topographic organization was appreciated only for tectal projections to the lateral subnucleus (PTh-l), which also receives sparse retinal projections. In contrast, the medial subnucleus receives fibers only from the medial tectum. We found that the PTh projects to nine subregions in the dorsal telencephalon and four in the ventral telencephalon. Furthermore, cerebellar injections revealed that cerebello-prethalamic fibers cross the midline twice to innervate the PTh-l on both sides. The present study is the first detailed report on the full set of the connections of PTh, which suggests that the PTh relays visual information from the optic tectum to the telencephalon., (© 2020 Wiley Periodicals, Inc.)

The thalamus consists of several functionally distinct nuclei, some of which serve as targets for functional neurosurgery. Visualization of such nuclei is a major challenge due to their low signal contrast on conventional imaging. We introduce MR susceptibility imaging with a short TE, leveraging susceptibility differences among thalamic nuclei, to automatically delineate 15 thalamic subregions. The technique has the potential to enable direct targeting of thalamic nuclei for functional neurosurgical guidance., (© 2020 by American Journal of Neuroradiology.)

Thalamic alterations occur in many neurological disorders including Alzheimer's disease, Parkinson's disease and multiple sclerosis. Routine interventions to improve symptom severity in movement disorders, for example, often consist of surgery or deep brain stimulation to diencephalic nuclei. Therefore, accurate delineation of grey matter thalamic subregions is of the upmost clinical importance. MRI is highly appropriate for structural segmentation as it provides different views of the anatomy from a single scanning session. Though with several contrasts potentially available, it is also of increasing importance to develop new image segmentation techniques that can operate multi-spectrally. We hereby propose a new segmentation method for use with multi-modality data, which we evaluated for automated segmentation of major thalamic subnuclear groups using T 1 -weighted, T 2 * -weighted and quantitative susceptibility mapping (QSM) information. The proposed method consists of four steps: Highly iterative image co-registration, manual segmentation on the average training-data template, supervised learning for pattern recognition, and a final convex optimisation step imposing further spatial constraints to refine the solution. This led to solutions in greater agreement with manual segmentation than the standard Morel atlas based approach. Furthermore, we show that the multi-contrast approach boosts segmentation performances. We then investigated whether prior knowledge using the training-template contours could further improve convex segmentation accuracy and robustness, which led to highly precise multi-contrast segmentations in single subjects. This approach can be extended to most 3D imaging data types and any region of interest discernible in single scans or multi-subject templates., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

The authors report on and discuss the historical evolution of the 3 intellectual and scientific domains essential for the current understanding of the function of the human thalamus: 1) the identification of the thalamus as a distinct anatomical and functional entity, 2) the subdivision of thalamic gray matter into functionally homogeneous units (the thalamic nuclei) and relative disputes about nuclei nomenclature, and 3) experimental physiology and its limitations.Galen was allegedly the first to identify the thalamus. The etymology of the term remains unknown although it is hypothesized that Galen may have wanted to recall the thalamus of Odysseus. Burdach was the first to clearly and systematically define the thalamus and its macroscopic anatomy, which paved the way to understanding its internal microarchitecture. This structure in turn was studied in both nonhuman primates (Friedemann) and humans (Vogt and Vogt), leading to several discrepancies in the findings because of interspecies differences. As a consequence, two main nomenclatures developed, generating sometimes inconsistent (or nonreproducible) anatomo-functional correlations. Recently, considerable effort has been aimed at producing a unified nomenclature, based mainly on functional data, which is indispensable for future developments. The development of knowledge about macro- and microscopic anatomy has allowed a shift from the first galenic speculations about thalamic function (the "thalamus opticorum nervorum") to more detailed insights into the sensory and motor function of the thalamus in the 19th and 20th centuries. This progress is mostly the result of lesion and tracing studies. Direct evidence of the in vivo function of the human thalamus, however, originates from awake stereotactic procedures only.Our current knowledge about the function of the human thalamus is the result of a long process that occurred over several centuries and has been inextricably intermingled with the increasing accumulation of data about thalamic macro- and microscopic anatomy. Although the thalamic anatomy can currently be considered well understood, further studies are still needed to gain a deeper insight into the function of the human thalamus in vivo.

The thalamus is 1 of 4 major divisions of the forebrain and is usually subdivided into epithalamus, dorsal thalamus, and ventral thalamus. The 39 gray matter regions comprising the large dorsal thalamus project topographically to the cerebral cortex, whereas the much smaller epithalamus (2 regions) and ventral thalamus (5 regions) characteristically project subcortically. Before analyzing extrinsic inputs and outputs of the thalamus, here, the intrinsic connections among all 46 gray matter regions of the rat thalamus on each side of the brain were expertly collated and subjected to network analysis. Experimental axonal pathway-tracing evidence was found in the neuroanatomical literature for the presence or absence of 99% of 2,070 possible ipsilateral connections and 97% of 2,116 possible contralateral connections; the connection density of ipsilateral connections was 17%, and that of contralateral connections 5%. One hub, the reticular thalamic nucleus (of the ventral thalamus), was found in this network, whereas no high-degree rich club or clear small-world features were detected. The reticular thalamic nucleus was found to be primarily responsible for conferring the property of complete connectedness to the intrathalamic network in the sense that there is, at least, one path of finite length between any 2 regions or nodes in the network. Direct comparison with previous investigations using the same methodology shows that each division of the forebrain (cerebral cortex, cerebral nuclei, thalamus, hypothalamus) has distinct intrinsic network topological organization. A future goal is to analyze the network organization of connections within and among these 4 divisions of the forebrain., Competing Interests: The authors declare no conflict of interest.

The thalamus and its nuclei are largely indistinguishable on standard T1 or T2 weighted MRI. While diffusion tensor imaging based methods have been proposed to segment the thalamic nuclei based on the angular orientation of the principal diffusion tensor, these are based on echo planar imaging which is inherently limited in spatial resolution and suffers from distortion. We present a multi-atlas segmentation technique based on white-matter-nulled MP-RAGE imaging that segments the thalamus into 12 nuclei with computation times on the order of 10 min on a desktop PC; we call this method THOMAS (THalamus Optimized Multi Atlas Segmentation). THOMAS was rigorously evaluated on 7T MRI data acquired from healthy volunteers and patients with multiple sclerosis by comparing against manual segmentations delineated by a neuroradiologist, guided by the Morel atlas. Segmentation accuracy was very high, with uniformly high Dice indices: at least 0.85 for large nuclei like the pulvinar and mediodorsal nuclei and at least 0.7 even for small structures such as the habenular, centromedian, and lateral and medial geniculate nuclei. Volume similarity indices ranged from 0.82 for the smaller nuclei to 0.97 for the larger nuclei. Volumetry revealed that the volumes of the right anteroventral, right ventral posterior lateral, and both right and left pulvinar nuclei were significantly lower in MS patients compared to controls, after adjusting for age, sex and intracranial volume. Lastly, we evaluated the potential of this method for targeting the Vim nucleus for deep brain surgery and focused ultrasound thalamotomy by overlaying the Vim nucleus segmented from pre-operative data on post-operative data. The locations of the ablated region and active DBS contact corresponded well with the segmented Vim nucleus. Our fast, direct structural MRI based segmentation method opens the door for MRI guided intra-operative procedures like thalamotomy and asleep DBS electrode placement as well as for accurate quantification of thalamic nuclear volumes to follow progression of neurological disorders., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Ascending Reticular Activating System (ARAS) has a key role in consciousness. The ARAS is a complex network consisting of a portion of the brainstem reticular formation, nonspecific thalamic nuclei, hypothalamus, Basal Forebrain (BF), and cerebral cortex. We examined the reconstruction method and features of the neural tract between the hypothalamus and the BF in normal subjects, using Diffusion Tensor Tractography (DTT)., Methods: Twenty-three healthy subjects were recruited. The ARAS between the hypothalamus and the BF was reconstructed by two Regions of Interest (ROIs): 1) seed ROI - the isolated green portion for the BF on the color map, 2) target ROI - the hypothalamus on the axial image. DTT parameters of the ARAS between the hypothalamus and the BF were examined., Results: Among 46 hemispheres in 23 normal subjects, 24 hemispheres (52.2 %) were identified in the ARAS between the hypothalamus and the BF. The reconstructed ARAS between the hypothalamus and the BF connected from the hypothalamus to the commissural level and anteriorly through the anterior commissure and then reached the BF., Conclusion: Using DTT, the ARAS between the hypothalamus and the BF was identified in normal subjects. Because the hypothalamus and BF are related to the regulation of wakefulness and sleep, our reconstruction method and results would be useful in the research on sleep and wakefulness aspects of consciousness., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The human thalamus is a brain structure that comprises numerous, highly specific nuclei. Since these nuclei are known to have different functions and to be connected to different areas of the cerebral cortex, it is of great interest for the neuroimaging community to study their volume, shape and connectivity in vivo with MRI. In this study, we present a probabilistic atlas of the thalamic nuclei built using ex vivo brain MRI scans and histological data, as well as the application of the atlas to in vivo MRI segmentation. The atlas was built using manual delineation of 26 thalamic nuclei on the serial histology of 12 whole thalami from six autopsy samples, combined with manual segmentations of the whole thalamus and surrounding structures (caudate, putamen, hippocampus, etc.) made on in vivo brain MR data from 39 subjects. The 3D structure of the histological data and corresponding manual segmentations was recovered using the ex vivo MRI as reference frame, and stacks of blockface photographs acquired during the sectioning as intermediate target. The atlas, which was encoded as an adaptive tetrahedral mesh, shows a good agreement with previous histological studies of the thalamus in terms of volumes of representative nuclei. When applied to segmentation of in vivo scans using Bayesian inference, the atlas shows excellent test-retest reliability, robustness to changes in input MRI contrast, and ability to detect differential thalamic effects in subjects with Alzheimer's disease. The probabilistic atlas and companion segmentation tool are publicly available as part of the neuroimaging package FreeSurfer., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

The thalamic reticular nucleus in reptiles, Caiman crocodilus, shares a number of morphological similarities with its counterpart in mammals. In view of the immunohistochemical properties of this nucleus in mammals and the more recently identified complexity of this neuronal aggregate in Caiman, this nucleus was investigated using a number of antibodies. These results were compared with findings described for other amniotes. The following antibodies gave consistent and reproducible results: polyclonal sheep anti-parvalbumin (PV), monoclonal mouse anti-PV, and polyclonal sheep anti-glutamic acid decarboxylase (GAD). In the transverse plane, this nucleus is divided into two. In each part, a compact group of cells sits on top of the fibers of the forebrain bundle with scattered cells among these fibers. In the lateral forebrain bundle, this neuronal aggregate is represented by the dorsal peduncular nucleus and the perireticular nucleus while, in the medial forebrain bundle, these parts are the interstitial nucleus and the scattered cells in this fiber tract. The results of this study are the following. First, the thalamic reticular nucleus of Caiman contains GAD(+) and PV(+) neurons, which is similar to what has been described in other amniotes. Second, the morphology and distribution of many GAD(+) and PV(+) neurons in the dorsal peduncular and perireticular nuclei are similar and suggest that these neurons colocalize these markers. Third, neurons in the interstitial nucleus and in the medial forebrain bundle are GAD(+) and PV(+). At the caudal pole of the thalamic reticular nucleus, PV immunoreactive cells predominated and avoided the central portion of this nucleus where GAD(+) cells were preferentially located. However, GAD(+) cells were sparse when compared with PV(+) cells. This immunohistochemically different area in the caudal pole is considered to be an area separate from the thalamic reticular nucleus., (© 2019 S. Karger AG, Basel.)

The auditory ascending system contains parallel pathways in vertebrate brains. In chickens (Gallus gallus), three pathways arise from nucleus laminaris (NL), nucleus angularis (NA), and regio intermedius (RI) in the brainstem, innervating three subdivisions of the nucleus mesencephalicus lateralis pars dorsalis (MLd) in the midbrain. The current study reveals the segregation of these pathways in their subsequent projections to the nucleus ovoidalis (Ov) in the thalamus. Based on cytoarchitecture and myelin distribution, we identified seven Ov subregions, including five neuronal clusters within the Ov proper, the nucleus semilunaris parovoidalis (SPO), and the circum-ovoidalis (cOv). Immunocytochemistry further revealed that a ventromedial cluster of the Ov proper (Ovvm) contains unique cell types expressing α8 subunit nicotinic acetylcholine receptor, while SPO and cOv are characterized with expression of calcitonin-gene-related peptide and cholecystokinin. Tract tracing studies demonstrated that Ovvm is a major target of the NL-recipient zone of MLd, while the RI-recipient zone of MLd predominantly projects to a ventrolateral cluster of the Ov proper. Afferent inputs to the remaining regions of the Ov proper mostly arise from the NA-recipient zone of MLd. SPO and cOv receive a projection from the surrounding areas of MLd, named the nucleus intercollicularis. Importantly, the Ov proper, SPO and cOv all project to the Field L2 in the forebrain, the avian auditory cortex. Taken together, these results demonstrate that the avian auditory thalamus is a structurally and functionally heterogeneous structure, implicating an important role in generating novel representations for specific acoustic features., (© 2017 Wiley Periodicals, Inc.)

The thalamus consists of multiple nuclei that have been previously defined by their chemoarchitectual and cytoarchitectual properties ex vivo. These form discrete, functionally specialized, territories with topographically arranged graduated patterns of connectivity. However, previous in vivo thalamic parcellation with MRI has been hindered by substantial inter-individual variability or discrepancies between MRI derived segmentations and histological sections. Here, we use the Euclidean distance to characterize probabilistic tractography distributions derived from diffusion MRI. We generate 12 feature maps by performing voxel-wise parameterization of the distance histograms (6 feature maps) and the distribution of three-dimensional distance transition gradients generated by applying a Sobel kernel to the distance metrics. We use these 12 feature maps to delineate individual thalamic nuclei, then extract the tractography profiles for each and calculate the voxel-wise tractography gradients. Within each thalamic nucleus, the tractography gradients were topographically arranged as distinct non-overlapping cortical networks with transitory overlapping mid-zones. This work significantly advances quantitative segmentation of the thalamus in vivo using 3T MRI. At an individual subject level, the thalamic segmentations consistently achieve a close relationship with a priori histological atlas information, and resolve in vivo topographic gradients within each thalamic nucleus for the first time. Additionally, these techniques allow individual thalamic nuclei to be closely aligned across large populations and generate measures of inter-individual variability that can be used to study both basic function and pathological processes in vivo., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

In our traditional view of the avian somatosensory system, input from the beak and head reaches the telencephalon via a disynaptic pathway, involving projections from the principal sensory nucleus (PrV) directly to nucleus basorostralis (previously called nucleus basalis), whereas input from the rest of the body follows a trisynatic pathway similar to that in mammals, involving projections from the dorsal column nuclei to the thalamus, and thence to somatosensory wulst. However, the role of the nuclei of the descending trigeminal tract (nTTD) in this scenario is unclear, partly because their ascending projections have been examined in only one species, the mallard duck. Here we examine the ascending projections of the nTTD in the zebra finch, using in vivo injections of biotinylated dextran amine and verification of projections by means of retrograde transport of the beta subunit of cholera toxin. The results show a high degree of interconnectivity within the nTTD, and that these nuclei project to PrV. We also find a projection from nTTD to the contralateral thalamic nucleus uvaeformis, a multi-sensory nucleus connected to the song system. Furthermore, our finding of a projection from nTTD to the contralateral somatosensory thalamic nucleus dorsalis intermedius ventralis anterior (DIVA) is consistent with the well-known projection in mammals from nTTD to the ventrobasal thalamus, suggesting that the ascending trigeminal pathways in birds and mammals are more similar than previously thought., (© 2017 Wiley Periodicals, Inc.)

The thalamus is an essential relay station in the cortical-subcortical connections. It is characterized by a complex anatomical architecture composed of numerous small nuclei, which mediate the involvement of the thalamus in a wide range of neurological functions. We present a novel framework for segmenting the thalamic nuclei, which explores the orientation distribution functions (ODFs) from diffusion magnetic resonance images at 3 T. The differentiation of the complex intra-thalamic microstructure is improved by using the spherical harmonic (SH) representation of the ODFs, which provides full angular characterization of the diffusion process in each voxel. The clustering was performed using the k-means algorithm initialized in a data-driven manner. The method was tested on 35 healthy volunteers and our results show a robust, reproducible and accurate segmentation of the thalamus in seven nuclei groups. Six of them closely matched the anatomy and were labeled as anterior, ventral anterior, medio-dorsal, ventral latero-ventral, ventral latero-dorsal and pulvinar, while the seventh cluster included the centro-lateral and the latero-posterior nuclei. Results were evaluated both qualitatively, by comparing the segmented nuclei to the histological atlas of Morel, and quantitatively, by measuring the clusters' extent and the clusters' spatial distribution across subjects and hemispheres. We also showed the robustness of our approach across different sequences and scanners, as well as intra-subject reproducibility of the segmented clusters using additional two scan-rescan datasets. We also observed an overlap between the path of the main long-connection tracts passing through the thalamus and the spatial distribution of the nuclei identified with our clustering algorithm. Our approach, based on SH representations of the ODFs, outperforms the one based on angular differences between the principle diffusion directions, which is considered so far as state-of-the-art method. Our findings show an anatomically reliable segmentation of the main groups of thalamic nuclei that could be of potential use in many clinical applications.

Dopaminergic reward dysfunction in addictive behaviors is well supported in the literature. There is evidence that alterations in synchronous neural activity between brain regions subserving reward and various cognitive functions may significantly contribute to substance-related disorders. This study presents the first evidence showing that a pro-dopaminergic nutraceutical (KB220Z) significantly enhances, above placebo, functional connectivity between reward and cognitive brain areas in the rat. These include the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, prelimbic and infralimbic loci. Significant functional connectivity, increased brain connectivity volume recruitment (potentially neuroplasticity), and dopaminergic functionality were found across the brain reward circuitry. Increases in functional connectivity were specific to these regions and were not broadly distributed across the brain. While these initial findings have been observed in drug naïve rodents, this robust, yet selective response implies clinical relevance for addicted individuals at risk for relapse, who show reductions in functional connectivity after protracted withdrawal. Future studies will evaluate KB220Z in animal models of addiction.

This protocol outlines large-scale reconstructions of neurons combined with the use of independent and unbiased clustering analyses to create a comprehensive survey of the morphological characteristics observed among a selective neuronal population. Combination of these techniques constitutes a novel approach for the collection and analysis of neuroanatomical data. Together, these techniques enable large-scale, and therefore more comprehensive, sampling of selective neuronal populations and establish unbiased quantitative methods for describing morphologically unique neuronal classes within a population. The protocol outlines the use of modified rabies virus to selectively label neurons. G-deleted rabies virus acts like a retrograde tracer following stereotaxic injection into a target brain structure of interest and serves as a vehicle for the delivery and expression of EGFP in neurons. Large numbers of neurons are infected using this technique and express GFP throughout their dendrites, producing "Golgi-like" complete fills of individual neurons. Accordingly, the virus-mediated retrograde tracing method improves upon traditional dye-based retrograde tracing techniques by producing complete intracellular fills. Individual well-isolated neurons spanning all regions of the brain area under study are selected for reconstruction in order to obtain a representative sample of neurons. The protocol outlines procedures to reconstruct cell bodies and complete dendritic arborization patterns of labeled neurons spanning multiple tissue sections. Morphological data, including positions of each neuron within the brain structure, are extracted for further analysis. Standard programming functions were utilized to perform independent cluster analyses and cluster evaluations based on morphological metrics. To verify the utility of these analyses, statistical evaluation of a cluster analysis performed on 160 neurons reconstructed in the thalamic reticular nucleus of the thalamus (TRN) of the macaque monkey was made. Both the original cluster analysis and the statistical evaluations performed here indicate that TRN neurons are separated into three subpopulations, each with unique morphological characteristics.

The last known Tasmanian tiger (Thylacinus cynocephalus)-aka the thylacine-died in 1936. Because its natural behavior was never scientifically documented, we are left to infer aspects of its behavior from museum specimens and historical recollections of bushmen. Recent advances in brain imaging have made it possible to scan postmortem specimens of a wide range of animals, even more than a decade old. Any thylacine brain, however, would be more than 100 years old. Here, we show that it is possible to reconstruct white matter tracts in two thylacine brains. For functional interpretation, we compare to the white matter reconstructions of the brains of two Tasmanian devils (Sarcophilus harrisii). We reconstructed the cortical projection zones of the basal ganglia and major thalamic nuclei. The basal ganglia reconstruction showed a more modularized pattern in the cortex of the thylacine, while the devil cortex was dominated by the putamen. Similarly, the thalamic projections had a more orderly topography in the thylacine than the devil. These results are consistent with theories of brain evolution suggesting that larger brains are more modularized. Functionally, the thylacine's brain may have had relatively more cortex devoted to planning and decision-making, which would be consistent with a predatory ecological niche versus the scavenging niche of the devil., Competing Interests: The authors have declared that no competing interests exist.

Sensory signals undergo substantial recoding when neural activity is relayed from sensors through pre-thalamic and thalamic nuclei to cortex. To explore how temporal dynamics and directional tuning are sculpted in hierarchical vestibular circuits, we compared responses of macaque otolith afferents with neurons in the vestibular and cerebellar nuclei, as well as five cortical areas, to identical three-dimensional translational motion. We demonstrate a remarkable spatio-temporal transformation: otolith afferents carry spatially aligned cosine-tuned translational acceleration and jerk signals. In contrast, brainstem and cerebellar neurons exhibit non-linear, mixed selectivity for translational velocity, acceleration, jerk and position. Furthermore, these components often show dissimilar spatial tuning. Moderate further transformation of translation signals occurs in the cortex, such that similar spatio-temporal properties are found in multiple cortical areas. These results suggest that the first synapse represents a key processing element in vestibular pathways, robustly shaping how self-motion is represented in central vestibular circuits and cortical areas., Competing Interests: The authors declare that no competing interests exist.

The thalamic reticular nucleus was investigated in one group of crocodilians, Caiman crocodilus. This neuronal aggregate is composed of two parts: a compact portion and a diffuse region made up of scattered cells within the forebrain bundles. In Caiman, both the lateral and medial forebrain bundles project to the telencephalon and the thalamic reticular nucleus is associated with each fiber tract. In the lateral forebrain bundle, the compact area is termed the nucleus of the dorsal peduncle (dorsal peduncular nucleus) while the diffuse part is called the perireticular area. In the medial forebrain bundle, the interstitial nucleus comprises one part of the compact area while another region without a specific neuronal label is also present. Similar to the perireticular cells of the lateral forebrain bundle, scattered cells are also present in the medial forebrain bundle. Morphological features of the thalamic reticular nucleus are revealed with stains for the following: fibers; cells; succinic acid dehydrogenase; and acetylcholinesterase. Regardless of which dorsal thalamic nucleus was injected, a localized region of the thalamic reticular nucleus contained retrogradely labeled cells and anterogradely labeled axons and terminals. This grouping was termed clusters and was felt to represent the densest interconnection between the dorsal thalamus and the reticular nucleus. Using clusters as an index of interconnections, the reticular nucleus was divided into sectors, each of which was associated with a specific dorsal thalamic nucleus. An organization similar to that found in Caiman is present in other sauropsids as well as in mammals. These data suggest that a thalamic reticular nucleus is present in all amniotes and has morphological properties similar to those described in this analysis. Lastly, a hypothesis is presented to explain how the external shape of the reticular nucleus in Caiman might be transformed into the homologous area in a representative bird and mammal., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objective: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) was recently introduced as treatment for movement disorders such as essential tremor and advanced Parkinson's disease (PD). Although deep brain target lesions are successfully generated in most patients, the target area temperature fails to increase in some cases. The skull is one of the greatest barriers to ultrasonic energy transmission. The authors analyzed the skull-related factors that may have prevented an increase in target area temperatures in patients who underwent MRgFUS., Methods: The authors retrospectively reviewed data from clinical trials that involved MRgFUS for essential tremor, idiopathic PD, and obsessive-compulsive disorder. Data from 25 patients were included. The relationships between the maximal temperature during treatment and other factors, including sex, age, skull area of the sonication field, number of elements used, skull volume of the sonication field, and skull density ratio (SDR), were determined., Results: Among the various factors, skull volume and SDR exhibited relationships with the maximum temperature. Skull volume was negatively correlated with maximal temperature (p = 0.023, r(2) = 0.206, y = 64.156 - 0.028x, whereas SDR was positively correlated with maximal temperature (p = 0.009, r(2) = 0.263, y = 49.643 + 11.832x). The other factors correlate with the maximal temperature, although some factors showed a tendency to correlate., Conclusions: Some skull-related factors correlated with the maximal target area temperature. Although the number of patients in the present study was relatively small, the results offer information that could guide the selection of MRgFUS candidates.

Higher-order motor cortices, such as the secondary motor area (M2) in rodents, select future action patterns and transmit them to the primary motor cortex (M1). To better understand motor processing, we characterized "top-down" and "bottom-up" connectivities between M1 and M2 in the rat cortex. Somata of pyramidal cells (PCs) in M2 projecting to M1 were distributed in lower layer 2/3 (L2/3) and upper layer 5 (L5), whereas PCs projecting from M1 to M2 had somata distributed throughout L2/3 and L5. M2 afferents terminated preferentially in upper layer 1 of M1, which also receives indirect basal ganglia output through afferents from the ventral anterior and ventromedial thalamic nuclei. On the other hand, M1 afferents terminated preferentially in L2/3 of M2, a zone receiving indirect cerebellar output through thalamic afferents from the ventrolateral nucleus. While L5 corticopontine (CPn) cells with collaterals to the spinal cord did not participate in corticocortical projections, CPn cells with collaterals to the thalamus contributed preferentially to connections from M2 to M1. L5 callosal projection (commissural) cells participated in connectivity between M1 and M2 bidirectionally. We conclude that the connectivity between M1 and M2 is directionally specialized, involving specific PC subtypes that selectively target lamina receiving distinct thalamocortical inputs., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The reuniens nucleus in the midline thalamus projects to the medial prefrontal cortex (mPFC) and the hippocampus, and has been suggested to modulate interactions between these regions, such as spindle-ripple correlations during sleep and theta band coherence during exploratory behavior. Feedback from the hippocampus to the nucleus reuniens has received less attention but has the potential to influence thalamocortical networks as a function of hippocampal activation. We used the retrograde tracer cholera toxin B conjugated to two fluorophores to study thalamic projections to the dorsal and ventral hippocampus and to the prelimbic and infralimbic subregions of mPFC. We also examined the feedback connections from the hippocampus to reuniens. The goal was to evaluate the anatomical basis for direct coordination between reuniens, mPFC, and hippocampus by looking for double-labeled cells in reuniens and hippocampus. In confirmation of previous reports, the nucleus reuniens was the origin of most thalamic afferents to the dorsal hippocampus, whereas both reuniens and the lateral dorsal nucleus projected to ventral hippocampus. Feedback from hippocampus to reuniens originated primarily in the dorsal and ventral subiculum. Thalamic cells with collaterals to mPFC and hippocampus were found in reuniens, across its anteroposterior axis, and represented, on average, about 8 % of the labeled cells in reuniens. Hippocampal cells with collaterals to mPFC and reuniens were less common (~1 % of the labeled subicular cells), and located in the molecular layer of the subiculum. The results indicate that a subset of reuniens cells can directly coordinate activity in mPFC and hippocampus. Cells with collaterals in the hippocampus-reuniens-mPFC network may be important for the systems consolidation of memory traces and for theta synchronization during exploratory behavior.

Interactions between the posterior cingulate cortex (areas 23 and 31) and the retrosplenial cortex (areas 29 and 30) with the anterior, laterodorsal and dorsal medial thalamic nuclei are thought to support various aspects of cognition, including memory and spatial processing. To detail these interactions better, the present study used retrograde tracers to reveal the origins of the corticothalamic projections in two closely related monkey species (Macaca mulatta, Macaca fascicularis). The medial dorsal thalamic nucleus received only light cortical inputs, which predominantly arose from area 23. Efferents to the anterior medial thalamic nucleus also arose principally from area 23, but these projections proved more numerous than those to the medial dorsal nucleus and also involved additional inputs from areas 29 and 30. The anterior ventral and laterodorsal thalamic nuclei had similar sources of inputs from the posterior cingulate and retrosplenial cortices. For both nuclei, the densest projections arose from areas 29 and 30, with numbers of thalamic inputs often decreasing when going dorsal from area 23a to 23c and to area 31. In all cases, the corticothalamic projections almost always arose from the deepest cortical layer. The different profiles of inputs to the anterior medial and anterior ventral thalamic nuclei reinforce other anatomical and electrophysiological findings suggesting that these adjacent thalamic nuclei serve different, but complementary, functions supporting memory. While the lack of retrosplenial connections singled out the medial dorsal nucleus, the very similar connection patterns shown by the anterior ventral and laterodorsal nuclei point to common roles in cognition., (© 2013 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The dorsolateral striatum (DLS) is critical for executing sensorimotor behaviors that depend on stimulus-response (S-R) associations. In rats, the DLS receives it densest inputs from primary somatosensory (SI) cortex, but it also receives substantial input from the thalamus. Much of rat DLS is devoted to processing whisker-related information, and thalamic projections to these whisker-responsive DLS regions originate from the parafascicular (Pf) and medial posterior (POm) nuclei. To determine which thalamic nucleus is better suited for mediating S-R associations in the DLS, we compared their input-output connections and neuronal responses to repetitive whisker stimulation. Tracing experiments demonstrate that POm projects specifically to the DLS, but the Pf innervates both dorsolateral and dorsomedial parts of the striatum. The Pf nucleus is innervated by whisker-sensitive sites in the superior colliculus, and these sites also send dense projections to the zona incerta, a thalamic region that sends inhibitory projections to the POm. These data suggest that projections from POm to the DLS are suppressed by incertal inputs when the superior colliculus is activated by unexpected sensory stimuli. Simultaneous recordings with two electrodes indicate that POm neurons are more responsive and habituate significantly less than Pf neurons during repetitive whisker stimulation. Response latencies are also shorter in POm than in Pf, which is consistent with the fact that Pf receives its whisker information via synaptic relays in the superior colliculus. These findings indicate that, compared with the Pf nucleus, POm transmits somatosensory information to the DLS with a higher degree of sensory fidelity.

Thalamic nuclei associated with language including the ventral lateral, ventral anterior, intralaminar and mediodorsal form a hub that uniquely receives the output of the basal ganglia and cerebellum, and is connected with frontal (premotor and prefrontal) cortices through two parallel circuits: a thalamic pathway targets the middle frontal cortical layers focally, and the other innervates widely cortical layer 1, poised to recruit other cortices and thalamic nuclei for complex cognitive operations. Return frontal pathways to the thalamus originate from cortical layers 6 and 5. Information through this integrated thalamo-cortical system is gated by the inhibitory thalamic reticular nucleus and modulated by dopamine, representing a specialization in primates. The intricate dialogue of distinct thalamic nuclei with the basal ganglia, cerebellum, and specific dorsolateral prefrontal and premotor cortices associated with language, suggests synergistic roles in the complex but seemingly effortless sequential transformation of cognitive operations for speech production in humans., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This study was designed to explore the electrophysiological relationships between the globus pallidus (GP), the substantia nigra pars reticulata (SNr) and the thalamic reticular nucleus (TRN) in urethane-anesthetized rats. The neuronal activity of the rostral part of the TRN was recorded by microelectrodes. Single pulse electrical stimulation of the GP and SNr produced inhibition of the spontaneous activity of the majority of TRN neurons. Stimulation of the GP by microinjections of bicuculline (25 ng/300 nl) produced also inhibition of the spontaneous activity of the reticular neurons. This could lead to facilitation of the cerebral cortex, as the reticular nucleus is reciprocally connected to, and inhibits, the thalamic motor nuclei, that in turn excite the motor cortex., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Dorsal horn neurons send ascending projections to both thalamic nuclei and parabrachial nuclei; these pathways are thought to be critical pathways for central processing of nociceptive information. Afferents from the corneal surface of the eye mediate nociception from this tissue which is susceptible to clinically important pain syndromes. This study examined corneal afferents to the trigeminal dorsal horn and compared inputs to thalamic- and parabrachial-projecting neurons. We used anterograde tracing with cholera toxin B subunit to identify corneal afferent projections to trigeminal dorsal horn, and the retrograde tracer FluoroGold to identify projection neurons. Studies were conducted in adult male Sprague-Dawley rats. Our analysis was conducted at two distinct levels of the trigeminal nucleus caudalis (Vc) which receive corneal afferent projections. We found that corneal afferents project more densely to the rostral pole of Vc than the caudal pole. We also quantified the number of thalamic- and parabrachial-projecting neurons in the regions of Vc that receive corneal afferents. Corneal afferent inputs to both groups of projection neurons were also more abundant in the rostral pole of Vc. Finally, by comparing the frequency of corneal afferent appositions to thalamic- versus parabrachial-projecting neurons, we found that corneal afferents preferentially target parabrachial-projecting neurons in trigeminal dorsal horn. These results suggest that nociceptive pain from the cornea may be primarily mediated by a non-thalamic ascending pathway., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

Repetitive electrical stimulation to the cortical masticatory areas (CMA) evokes rhythmical jaw movements (RJM), whose patterns vary depending on the stimulation site, in various species. In guinea pigs, although alternating bilateral jaw movements are usually seen during natural chewing, it is still unclear which cortical areas are responsible for chewing-like RJM. To address this issue, we first defined the cortical areas inducing chewing-like RJM by intracortical microstimulation. Stimulation of the most lateral area of the CMA, the granular cortex, induced chewing-like RJM, but from the region medial to this area, simple vertical RJM were induced. Subsequently, to reveal the properties of these two areas in the CMA, the connections between the CMA and the dorsal thalamus were examined by neuronal tract-tracing techniques. The area inducing chewing-like RJM possessed strong reciprocal connections, mainly with the medial part of the ventral posteromedial nucleus, which is the sensory-relay thalamus. On the other hand, the simple vertical RJM-inducing area had reciprocal connections with the motor thalamus. The present study suggests that the CMA inducing chewing-like RJM is different from the CMA inducing simple vertical RJM, and plays a role in cortically induced chewing-like RJM under the influence of the sensory thalamus in guinea pigs., (Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Distinct thalamic nuclei, like the mediodorsal (MD) nucleus and the centromedian/parafascicular complex (CM/Pf), are embedded in different basal ganglia-thalamocortical loops, which were shown to integrate cognitive and emotional aspects of human behavior. Despite well described connections on a microscopic scale, derived from tracing studies in animals, little is known about the intrinsic anatomical connections of these nuclei in humans. This lack of knowledge limits not only interpretation of functional imaging studies but also estimation of direct effects of deep brain stimulation which treats diseases as different as epilepsy or major depression. Therefore, non-invasive diffusion tensor imaging (DTI) studies are key to analyzing connectivity patterns and elaborate approaches to close this gap. For our study, we explored the structural connectivity of the MD thalamic nuclei and the CM/Pf complex towards five cortical and six subcortical regions by using a preferential fiber calculation. We found both thalamic nuclei to be preferentially associated to distinct networks: whereas the MD is preferentially connected to prefrontal and limbic cortical regions, the CM is linked to subcortical regions. The anterior insula was the only cortical region associated with the subcortical network of the CM and the cortical network of the MD comprised one subcortical hub, the caudate nucleus, suggesting an integrative role of these two regions. Adding to predescribed anatomical tract tracing connectivities in animal studies, our finding lends support to the existence of similar basal ganglia-thalamocortical circuits in humans and we could show a robust distinction of preferential connectivity for both thalamic nuclei., (Copyright © 2011 Wiley Periodicals, Inc.)

In mammals, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are the main components of the circadian timing system. The SCN is the site of the endogenous biological clock that generates rhythms and synchronizes them to environmental cues. The IGL is a key structure that modulates SCN activity and is responsible for the transmission of non-photic information to the SCN, thus participating in the integration between photic and non-photic stimuli. Both the SCN and IGL receive projections of retinal ganglion cells and the IGL is connected to the SCN through the geniculohypothalamic tract. Little is known about these structures in the primate brain and the pregeniculate nucleus (PGN) has been suggested to be the primate equivalent of the rodent IGL. The aim of this study was to characterize the PGN of a primate, the common marmoset (Callithrix jacchus), and to analyze its retinal afferents. Here, the marmoset PGN was found to be organized into three subsectors based on neuronal size, pattern of retinal projections, and the distribution of neuropeptide Y-, GAD-, serotonin-, enkephalin- and substance P-labeled terminals. This pattern indicates that the marmoset PGN is equivalent to the IGL. This detailed description contributes to the understanding of the circadian timing system in this primate species considering the importance of the IGL within the context of circadian regulation., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Advances in mouse neural circuit genetics, brain atlases, and behavioral assays provide a powerful system for modeling the genetic basis of cognition and psychiatric disease. However, a critical limitation of this approach is how to achieve concordance of mouse neurobiology with the ultimate goal of understanding the human brain. Previously, the common marmoset has shown promise as a genetic model system toward the linking of mouse and human studies. However, the advent of marmoset transgenic approaches will require an understanding of developmental principles in marmoset compared to mouse. In this study, we used gene expression analysis in marmoset brain to pose a series of fundamental questions on cortical development and evolution for direct comparison to existing mouse brain atlas expression data. Most genes showed reliable conservation of expression between marmoset and mouse. However, certain markers had strikingly divergent expression patterns. The lateral geniculate nucleus and pulvinar in the thalamus showed diversification of genetic organization between marmoset and mouse, suggesting they share some similarity. In contrast, gene expression patterns in early visual cortical areas showed marmoset-specific expression. In prefrontal cortex, some markers labeled architectonic areas and layers distinct between mouse and marmoset. Core hippocampus was conserved, while afferent areas showed divergence. Together, these results indicate that existing cortical areas are genetically conserved between marmoset and mouse, while differences in areal parcellation, afferent diversification, and layer complexity are associated with specific genes. Collectively, we propose that gene expression patterns in marmoset brain reveal important clues to the principles underlying the molecular evolution of cortical and cognitive expansion.

The subcortical projections to the marmoset frontal pole were mapped with the use of fluorescent tracer injections. The main thalamic projections, which originated in both the magnocellular and parvocellular subdivisions of the mediodorsal nucleus, were topographically organized. Our results suggest the existence of a third, caudal subdivision of this nucleus, which is likely to be homologous to the macaque's pars densocellularis. A substantial, but not topographically organized, projection to Brodmann's area 10 originated in the medial part of the ventral anterior nucleus. Minor thalamic projections originated in the medial pulvinar nucleus and in the midline/intralaminar nuclei. Finally, the posterior thalamic group (including the limitans and suprageniculate nuclei) sent a small projection to rostral area 10 that has not previously been documented in primates. The main extrathalamic projections stemmed from the claustrum, which contained as many as 50% of all subcortical labelled neurons. Minor connections originated in the hypothalamus (mainly in the lateral anterior and lateral tuberal regions), dorsal periaqueductal grey matter, basal forebrain (nucleus basalis of Meynert and horizontal limb of the diagonal band of Broca), and amygdala (basal, accessory basal and lateral nuclei). The present results, combined with recent data on the cortical projections to area 10, reveal the frontal pole as a region that integrates information from multiple neural processing systems, including high-level sensory, limbic and working memory-related structures. Although the pattern of subcortical projections is similar to that previously described in the macaque, suggesting a homologous organization, the present data also suggest functional distinctions between medial and lateral sectors of area 10., (© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

Reliable identification of thalamic nuclei is required to improve positioning of electrodes in Deep Brain Stimulation (DBS), and to allow the role of individual thalamic nuclei in health and disease to be fully investigated. In this work, a previously proposed method for identifying sub-regions within the thalamus based on differences in their T1 and T2 values is explored in detail. The effect on the segmentation of T1 and T2 dependence weighted against priors for spatial position and extent was investigated. When T1 and T2 dependence was highly weighted, good distinction between identified regions was obtained in T1/T2 feature-space, but no contiguous anatomically distinct regions were identified within the thalamus. Incorporating spatial priors was necessary to ensure anatomically distinct regions were defined. Optimal values for segmentation parameters were obtained by assessing performance on a 'synthetic thalamus'. Using these optimum input parameters, within- and between-subjects reproducibility was assessed. Good reproducibility was obtained when six regions were specified to be identified in the thalamus. The six regions identified were similar in the majority of the normal subject group. However, intriguingly these regions were different from those obtained in the same subjects using a well-known connectivity-based segmentation technique. This method shows promise to identify intrathalamic structures on the basis of T1 and T2 signal. A comprehensive characterisation of thalamic nuclei may require a fully multi-modal approach., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The architectonic features of the ventroposterior nucleus (VP) were visualized in coronal brain sections from two macaque monkeys, two owl monkeys, two squirrel monkeys, and three galagos that were processed for cytochrome oxidase, Nissl bodies, or the vesicular glutamate transporter 2 (vGluT2). The traditional ventroposterior medial (VPM) and ventroposterior lateral (VPL) subnuclei were easily identified, as well as the forelimb and hindlimb compartments of VPL, as they were separated by poorly staining, cell-poor septa. Septa also separated other cell groups within VPM and VPL, specifically in the medial compartment of VPL representing the hand (hand VPL). In one squirrel monkey and one galago we demonstrated that these five groups of cells represent digits 1-5 in a mediolateral sequence by injecting tracers into the cortical representation of single digits, defined by microelectrode recordings, and relating concentrations of labeled neurons to specific cell groups in hand VPL. The results establish the existence of septa that isolate the representation of the five digits in VPL of primates and demonstrate that the isolated cell groups represent digits 1-5 in a mediolateral sequence. The present results show that the septa are especially prominent in brain sections processed for vGluT2, which is expressed in the synaptic terminals of excitatory neurons in most nuclei of the brainstem and thalamus. As vGluT2 is expressed in the synaptic terminations from dorsal columns and trigeminal brainstem nuclei, the effectiveness of vGluT2 preparations in revealing septa in VP likely reflects a lack of synapses using glutamate in the septa., (Copyright © 2010 Wiley-Liss, Inc.)

Motor thalamic nuclei, ventral anterior (VA), ventral lateral (VL) and ventral medial (VM) nuclei, receive massive glutamatergic and GABAergic afferents from the cerebellum and basal ganglia, respectively. In the present study, these afferents were characterized with immunoreactivities for glutamic acid decarboxylase of 67 kDa (GAD67) and vesicular glutamate transporter (VGluT)2, and examined by combining immunocytochemistry with the anterograde axonal labeling and neuronal depletion methods in the rat brain. VGluT2 immunoreactivity was intense in the caudodorsal portion of the VA-VL, whereas GAD67 immunoreactivity was abundant in the VM and rostroventral portion of the VA-VL. The rostroventral VA-VL and VM contained two types of GAD67-immunopositive varicosities (large and small), but the caudodorsal VA-VL comprised small ones alone. VGluT2-immunopositive varicosities were much larger in the caudodorsal VA-VL than those in the rostroventral VA-VL and VM. When anterograde tracers were injected into the basal ganglia output nuclei, the vast majority of labeled axon varicosities were large and distributed in the rostroventral VA-VL and VM, showing immunoreactivity for GAD67, but not for VGluT2. Only the large GAD67-immunopositive varicosities were mostly abolished by kainic acid depletion of substantia nigra neurons. In contrast, large to giant axon varicosities derived from the deep cerebellar nuclei were distributed mostly in the caudodorsal VA-VL, displaying VGluT2 immunoreactivity. The VGluT2-positive varicosities disappeared from the core portion of the caudodorsal VA-VL by depletion of cerebellar nucleus neurons. Thus, complementary distributions of large VGluT2- and GAD67-positive terminals in the motor thalamic nuclei are considered to reflect glutamatergic cerebellar and GABAergic basal ganglia afferents, respectively., (© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

The chemoanatomical organization of the visual sector of the cat's thalamic reticular nucleus (TRN)-that is at the dorsal lateral geniculate nucleus (dLGN) and at the pulvinar nucleus (Pul)-was investigated with two novel cytoarchitectonic markers. The Wisteria floribunda agglutinin (WFA) binding reaction visualized the extracellular perineuronal net (PN) and the SMI 32 immunoreaction stained intracellular neurofilaments. Two distinct layers of the TRN could be detected, particularly by WFA- but also by SMI 32-staining. The outer tier outlined a canopy of labeling placed a bit detached from the diencephalon dorsolaterally, while the inner TRN tier is very tightly attached to the thalamic lamina limitans externa. The labeled neurons showed typically fusiform morphology with dendrites orienting in the plane of TRN. Additionally, these chemoarchitectural reactions identified a chain of structures in the ventral diencephalon connected to the TRN tiers. One stained string is formed by the subthalamic nucleus bound laterally to the peripeduncular nucleus extending further dorsolateral into the outer TRN tier. The other chain laced up the field of Forel, the zona incerta, the ventral LGN, the perigeniculate nucleus (PGN) and the previously-overlooked peripulvinar nucleus (PPulN) and so formed the inner TRN tier. In the third most distanced TRN tier, in the perireticular nucleus, a very few WFA-binding presenting neuron were found. In addition to the PN possessing TRN neurons, WFA-reactive presumable interneurons were also labeled within the visual thalamus. Following tracer injections into the feline Pul, two stripes of cells were retrogradely labeled in the neighboring visual TRN sector. The location of these reticular neurons coincided precisely with the chemoanatomically identified inner and outer TRN tiers. On the analogy of the PGN-TRN duality at the dLGN, the chemoanatomical and tract tracing findings strongly suggest a similar dual organization in the pulvinoprojecting TRN portion., (Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.)

The prefrontal cortex projects to many thalamic nuclei, in pathways associated with cognition, emotion, and action. We investigated how multiple projection systems to the thalamus are organized in prefrontal cortex after injection of distinct retrograde tracers in the principal mediodorsal (MD), the limbic anterior medial (AM), and the motor-related ventral anterior/ventral lateral (VA/VL) thalamic nuclei in rhesus monkeys. Neurons projecting to these nuclei were organized in interdigitated modules extending vertically within layers VI and V. Projection neurons were also organized in layers. The majority of projection neurons to MD or AM originated in layer VI ( approximately 80%), but a significant proportion ( approximately 20%) originated in layer V. In contrast, prefrontal neurons projecting to VA/VL were equally distributed in layers V and VI. Neurons directed to VA/VL occupied mostly the upper part of layer V, while neurons directed to MD or AM occupied mostly the deep part of layer V. The highest proportions of projection neurons in layer V to each nucleus were found in dorsal and medial prefrontal areas. The laminar organization of prefrontal cortico-thalamic projections differs from sensory systems, where projections originate predominantly or entirely from layer VI. Previous studies indicate that layer V cortico-thalamic neurons innervate through some large terminals thalamic neurons that project widely to superficial cortical layers. The large population of prefrontal projection neurons in layer V may drive thalamic neurons, triggering synchronization by recruiting several cortical areas through widespread thalamo-cortical projections to layer I. These pathways may underlie the synthesis of cognition, emotion and action.

The primary goal of this study was to examine whether the locus coeruleus (LC) provides collateral projections to whisker-related, sensorimotor brain regions. After injections of retrograde tracers into the primary sensory (S1) barrel field/primary whisker motor (M1) cortices, ventroposteromedial (VPM)/ventrolateral (VL) thalamic nuclei, or principal sensory trigeminal (Pr5)/facial motor (Mo7) nuclei, the distribution of double-labeled neurons within the LC was examined. Our observations indicated that a large number of individual LC cells provided axon collaterals to S1-M1 or VPM-VL regions, whereas only a few projected to Pr5-Mo7 nuclei. The laterality and the distribution of dual-projecting LC neurons were as follows. 1) The neurons projecting to the S1-M1 cortices were predominantly ipsilateral (96% +/- 0.7%). Labeled neurons were located ventrally at the rostral pole but were evenly distributed along the dorsoventral aspect of the principal LC. 2) The cells projecting to the VPM-VL nuclei were bilateral, with ipsilateral (68% +/- 2.3%) dominance. Neurons were observed at the rostrocaudal extent of the LC, where the labeling was most pronounced at the ventral, principal LC. 3) The neurons projecting to the Pr5-Mo7 regions exhibited slightly contralateral (56% +/- 2.9%) dominance, where labeled cells were confined within the ventral margin of the principal subdivision. Taken together, the present observations demonstrate that each subdivision of the LC possesses a differential functional organization with respect to its collateral projection to whisker-related sensorimotor targets, suggesting that the nucleus might play a modulatory role in vibrissal sensorimotor integration that allows the guidance of behavioral action essential for the survival of the animal.

In two turtle species--Emys orbicularis and Testudo horsfieldi--by the method of anterograde and retrograde traicing method at the light and electron microscopy level, the existence is proven of direct descending projections from the thalamic nucleus of the tectofugal visual system n. rotunds (Rot) to the optic tectum. After injection of tracers into Rot alone and into Rot with involvement of the tectothalamic tract (Trtth), occasional labeled fibers with varicosities and terminals are revealed predominantly in the deep sublayers of SGFS of the rostral optic tectum, while in the lower amount in other tectal layers. After the tracer injections into the optic tectum, a few retrogradely labeled neurons were found mainly in the Rot ventral parts and within Trtth. Their localization coincides with that of GABA-immunoreactive cells. Electron microscopy showed the existence of many retrogradely labeled dendrites throughout the whole Rot; a few labeled cell bodies were also present there, some of them being also GABA-immunoreactive. These results allow us to conclude about the existence of reciprocal connections between the optic tectum and Rot in turtles, these connections being able to affect processing of visual information in tectum. We suggest that reciprocity of tectothalamic connections might be the ancestral feature of the vertebrate brain; in the course of amniote evolution the functional significance of this feature can be decreased and even lost in parallel with a rise of the role of direct corticotectal projections.

The basal ganglia consist of the striatum, which includes the caudate-putamen and the core of the nucleus accumbens, the external segment of the globus pallidus (GPe), the subthalamic nucleus, the internal segment of the globus pallidus (GPi), and the substantia nigra (SN). The major input to the basal ganglia is glutamatergic striatopetal projections from nearly all areas of the neocortex and the intralaminar and midline nuclei. The striatofugal projection neurons are divided into 2 groups; one includes neurons projecting to the SN and GPi, and the other includes those projecting to the GPe. The former neurons are called 'direct pathway' neurons in the basal ganglia circuit, since they directly extend their axons to the output nuclei of the basal ganglia, i.e. pars reticulata of the SN (SNr) and GPi. On the other hand, the latter striato-GPe neurons are called 'indirect pathway' neurons and contain striato-GPe, GPe-subthalamic, and subthalamo-GPi/SNr projections. The output of the basal ganglia is the projection of GABAergic neurons in the GPe and SNr. In addition to the 2 segregated striatofugal groups, the neostriatum possesses a mosaic organization composed of patch and matrix compartments. The patch compartment occupies 10-15% of the neostriatal volume and is characterized by its projection to the pars compacta of the SN (SNc). The basal ganglia output targets the thalamic nuclei, which are part of cortico-basal ganglia circuits, the intermediate layers of the superior colliculus, and the pedunculopontine nucleus. The basal ganglia possess not only the topographic organization that provides parallel and functionally defined loops but also the divergence and convergence connections, which may reflect the organizational features of the basal ganglia.

Background: The Drosophila Shaker mutant fruit-fly, with its malfunctioning voltage-gated potassium channel, exhibits anesthetic requirements that are more than twice normal. Shaker mutants with an abnormal Kv1.2 channel also demonstrate significantly reduced sleep. Given the important role the thalamus plays in both sleep and arousal, the authors investigated whether localized central medial thalamic (CMT) microinfusion of an antibody designed to block the pore of the Kv1.2 channel might awaken anesthetized rats., Methods: Male Sprague-Dawley rats were implanted with a cannula aimed at the CMT or lateral thalamus. One week later, unconsciousness was induced with either desflurane (3.6 +/- 0.2%; n = 55) or sevoflurane (1.2 +/- 0.1%; n = 51). Arousal effects of a single 0.5-microl infusion of Kv1.2 potassium channel blocking antibody (0.1- 0.2 mg/ml) or a control infusion of Arc-protein antibody (0.2 mg/ml) were then determined., Results: The Kv1.2 antibody, but not the control antibody, temporarily restored consciousness in 17% of all animals and in 75% of those animals where infusions occurred within the CMT (P < 0.01 for each anesthetic). Lateral thalamic infusions showed no effects. Consciousness returned on average (+/- SD) 170 +/- 99 s after infusion and lasted a median time of 398 s (interquartile range: 279-510 s). Temporary seizures, without apparent consciousness, predominated in 33% of all animals., Conclusions: These findings support the idea that the CMT plays a role in modulating levels of arousal during anesthesia and further suggest that voltage-gated potassium channels in the CMT may contribute to regulating arousal or may even be relevant targets of anesthetic action.

In addition to the cerebral cortex, the striatum receives excitatory input from the thalamus. The centromedian (centre median, CM) and parafascicular (Pf) nuclei are an important source of thalamostriatal projections. Anterograde tract-tracing indicates the CM-Pf complex provides dense afferents to the matrix compartment of the striatum. Whereas CM projects to the entire sensorimotor territory of the striatum, the Pf provides complementary input to the entire associative sector. The Pf also provides lighter input to the nucleus accumbens. Both CM and Pf provide light to moderately dense inputs to other components of the basal ganglia in a largely complementary manner, covering motor or associative-limbic territories of the subthalamic nucleus, globus pallidus and ventral midbrain. In turn, the CM and Pf receive mainly segregated input from parallel motor and associative-limbic circuits of the basal ganglia. The CM and Pf may therefore be considered important participants in parallel processing of motor and associative-limbic information in the basal ganglia. Connections of the CM and Pf with other thalamic nuclei suggest they also participate in integrative functions within the thalamus. In addition, inputs from the brainstem reticular core, reciprocal connections with the cerebral cortex and reticular thalamic nucleus suggest a role in state-dependant information processing. Consideration of the differential connections of the CM and Pf, and better understanding of their role in pathophysiology, may eventually lead to development of an important new target for relief of a variety of neurological and psychiatric disorders.