Search

A unique population of ventral tegmental area (VTA) neurons co-transmits glutamate and GABA. However, the circuit inputs to VTA VGluT2+VGaT+ neurons are unknown, limiting our understanding of their functional capabilities. By coupling monosynaptic rabies tracing with intersectional genetic targeting in male and female mice, we found that VTA VGluT2+VGaT+ neurons received diverse brainwide inputs. The largest numbers of monosynaptic inputs to VTA VGluT2+VGaT+ neurons were from superior colliculus (SC), lateral hypothalamus (LH), midbrain reticular nucleus, and periaqueductal gray, whereas the densest inputs relative to brain region volume were from the dorsal raphe nucleus, lateral habenula, and VTA. Based on these and prior data, we hypothesized that LH and SC inputs were from glutamatergic neurons. Optical activation of glutamatergic LH neurons activated VTA VGluT2 +VGaT+ neurons regardless of stimulation frequency and resulted in flee-like ambulatory behavior. In contrast, optical activation of glutamatergic SC neurons activated VTA VGluT2+VGaT+ neurons for a brief period of time at high frequency and resulted in head rotation and arrested ambulatory behavior (freezing). Stimulation of glutamatergic LH neurons, but not glutamatergic SC neurons, was associated with VTA VGluT2+VGaT+ footshock-induced activity and inhibition of LH glutamatergic neurons disrupted VTA VGluT2+VGaT+ tailshock-induced activity. We interpret these results such that inputs to VTA VGluT2+VGaT+ neurons may integrate diverse signals related to the detection and processing of motivationally salient outcomes. [ABSTRACT FROM AUTHOR]

Dorsal human midbrain contains two nuclei with clear laminar organization, the superior and inferior colliculi. These nuclei extend in depth between the superficial dorsal surface of midbrain and a deep midbrain nucleus, the periaqueductal gray matter (PAG). The PAG, in turn, surrounds the cerebral aqueduct (CA). This study examined the use of two depth metrics to characterize depth and thickness relationships within dorsal midbrain using the superficial surface of midbrain and CA as references. The first utilized nearest-neighbor Euclidean distance from one reference surface, while the second used a level-set approach that combines signed distances from both reference surfaces. Both depth methods provided similar functional depth profiles generated by saccadic eye movements in a functional MRI task, confirming their efficacy for delineating depth for superficial functional activity. Next, the boundaries of the PAG were estimated using Euclidean distance together with elliptical fitting, indicating that the PAG can be readily characterized by a smooth surface surrounding PAG. Finally, we used the level-set approach to measure tissue depth between the superficial surface and the PAG, thus characterizing the variable thickness of the colliculi. Overall, this study demonstrates depth-mapping schemes for human midbrain that enables accurate segmentation of the PAG and consistent depth and thickness estimates of the superior and inferior colliculi.

The caudal colliculus serves as an integrative station and switchboard, controlling nucleus of lower auditory pathway and motor‐auditory reflex production. The rostral colliculus coordinates reflexive movement of the head, neck, eye and focus the lens for visual tracking of objects. There is no information comparing mesencephalic tectum among neonates, juveniles and adults of African giant rat (AGR). Hence, this study aimed to compare the gross features and morphometric parameters of mesencephalic tectum postnatally in AGR. The following were found and reported: (a) Paired dorsal tips of caudal colliculi were observed through transverse fissure of the intact brain and so, corpora quadrigemina were partly occluded by cerebral cortex in neonates and juveniles. (b) The lateral and medial geniculate bodies were visible, though the lateral was grossly bigger than the medial in adults and juveniles but, only the lateral was distinguishable in neonates. (c) Live body weight, absolute brain weight, caudal colliculus width, nose–rump and tail lengths increased as AGRs developed with age; mean values of rostral colliculus weight, caudal colliculus height and weight of caudal colliculus in neonates and juveniles were statistically same; while midbrain weight and rostral colliculus height tends to decrease as rats aged. (d) The mean weight of caudal colliculi and width of rostral colliculi were not affected by age. (e) Caudal colliculi were grossly wider than rostral in juveniles and adults, but not neonates. Established regression formulae are necessary to avoid future sacrifice of this rodent. [ABSTRACT FROM AUTHOR]

It has become widely accepted that humans use contextual information to infer the meaning of ambiguous acoustic signals. In speech, for example, high-level semantic, syntactic, or lexical information shape our understanding of a phoneme buried in noise. Most current theories to explain this phenomenon rely on hierarchical predictive coding models involving a set of Bayesian priors emanating from high-level brain regions (e.g., prefrontal cortex) that are used to influence processing at lower-levels of the cortical sensory hierarchy (e.g., auditory cortex). As such, virtually all proposed models to explain top-down facilitation are focused on intracortical connections, and consequently, subcortical nuclei have scarcely been discussed in this context. However, subcortical auditory nuclei receive massive, heterogeneous, and cascading descending projections at every level of the sensory hierarchy, and activation of these systems has been shown to improve speech recognition. It is not yet clear whether or how top-down modulation to resolve ambiguous sounds calls upon these corticofugal projections. Here, we review the literature on top-down modulation in the auditory system, primarily focused on humans and cortical imaging/recording methods, and attempt to relate these findings to a growing animal literature, which has primarily been focused on corticofugal projections. We argue that corticofugal pathways contain the requisite circuitry to implement predictive coding mechanisms to facilitate perception of complex sounds and that top-down modulation at early (i.e., subcortical) stages of processing complement modulation at later (i.e., cortical) stages of processing. Finally, we suggest experimental approaches for future studies on this topic.

It has become widely accepted that humans use contextual information to infer the meaning of ambiguous acoustic signals. In speech, for example, high-level semantic, syntactic, or lexical information shape our understanding of a phoneme buried in noise. Most current theories to explain this phenomenon rely on hierarchical predictive coding models involving a set of Bayesian priors emanating from high-level brain regions (e.g., prefrontal cortex) that are used to influence processing at lower-levels of the cortical sensory hierarchy (e.g., auditory cortex). As such, virtually all proposed models to explain top-down facilitation are focused on intracortical connections, and consequently, subcortical nuclei have scarcely been discussed in this context. However, subcortical auditory nuclei receive massive, heterogeneous, and cascading descending projections at every level of the sensory hierarchy, and activation of these systems has been shown to improve speech recognition. It is not yet clear whether or how top-down modulation to resolve ambiguous sounds calls upon these corticofugal projections. Here, we review the literature on top-down modulation in the auditory system, primarily focused on humans and cortical imaging/recording methods, and attempt to relate these findings to a growing animal literature, which has primarily been focused on corticofugal projections. We argue that corticofugal pathways contain the requisite circuitry to implement predictive coding mechanisms to facilitate perception of complex sounds and that top-down modulation at early (i.e., subcortical) stages of processing complement modulation at later (i.e., cortical) stages of processing. Finally, we suggest experimental approaches for future studies on this topic. [ABSTRACT FROM AUTHOR]

Acoustically evoked seizures (e.g., audiogenic seizures or AGS) are common in models of inherited epilepsy and occur in a variety of species including rat, mouse, and hamster. Two models that have been particularly well studied are the genetically epilepsy prone rat (GEPR-3) and the Wistar Audiogenic Rat (WAR) strains. Acute and repeated AGS, as well as comorbid conditions, displays a close phenotypic overlap in these models. Whether these similarities arise from convergent or divergent structural changes in the brain remains unknown. Here, we examined the brain structure of Sprague Dawley (SD) and Wistar (WIS) rats, and quantified changes in the GEPR-3 and WAR, respectively. Brains from adult, male rats of each strain (n=8–10 per group) were collected, fixed, and embedded in agar and imaged using a 7 tesla Bruker MRI. Post-acquisition analysis included voxel-based morphometry (VBM), diffusion tensor imaging (DTI), and manual volumetric tracing. In the VBM analysis, GEPR-3 displayed volumetric changes in brainstem structures known to be engaged by AGS (e.g., superior and inferior colliculus, periaqueductal grey) and in forebrain structures (e.g., striatum, septum, nucleus accumbens). WAR displayed volumetric changes in superior colliculus, and a broader set of limbic regions (e.g., hippocampus, amygdala/piriform cortex). The only area of significant overlap in the two strains was the midline cerebellum: both GEPR-3 and WAR showed decreased volume compared to their control strains. In the DTI analysis, GEPR-3 displayed decreased fractional anisotropy (FA) in the corpus callosum, posterior commissure and commissure of the inferior colliculus (IC). WAR displayed increased FA only in the commissure of IC. These data provide a biological basis for further comparative and mechanistic studies in the GEPR-3 and WAR models, as well as provide additional insight into commonalities in the pathways underlying AGS susceptibility and behavioral comorbidity.

Most of neuroimaging applications tend to still rely on expert knowledge in determining anatomies of the brain. For example in Parkinson’s disease surgery, detection of the anterior commissure (AC) and posterior commissure (PC) are still done manually by doctors. Previously, various methods have been developed related to the automatic detection of AC and PC. However, the majority of previously methods have several drawbacks, such as only compatible on T1-W or T2-W, only compatible for data with the same matrix size, and requires a time-consuming training process. This study proposes a new strategy by combining a multilevel thresholding and morphological relationships approach for automatic detection of AC and PC. The process divided into 4 main stages: preprocessing, multilevel thresholding, segmentation, and detection of AC and PC. The segmentation is performed on several anatomies of the brain including corpus callosum, fornix, and colliculus. From the experiment, it can be concluded that the use of multilevel thresholding and morphological relationship was successfully detecting AC and PC with the mean error were 1.02 mm and 1.06 mm, respectively. The proposed method can perform an automatic detection of AC and PC with simply algorithm, does not require a large of diverse data sets for the training process, without training process that takes up time, and reliable on the diversity of MRI since it is compatible for T1-W and T2-W with various matrix sizes of 256 x 256 and 512 x 512 pixels which cannot be handled by previous researches [ABSTRACT FROM AUTHOR]

The lateral cortex of the inferior colliculus (LCIC) forms a nexus between diverse multisensory, motor, and neuromodulatory streams. Like other integration hubs, it contains repeated neurochemical motifs with distinct inputs: GABA-rich modules are innervated by somatosensory structures, while auditory inputs to the LCIC target the surrounding extramodular matrix. To investigate potential mechanisms of convergence between these input streams, we used laser photostimulation circuit mapping to interrogate local LCIC circuits in adult mice of both sexes and found that input patterns are highly dependent on cell type (GABAergic/non-GABAergic) and location (module/matrix). At the circuit level, these inputs yield a directional flow of local information, primarily from the matrix to the modules. Further, the two compartments were found to project to distinct targets in the midbrain and thalamus. These data show that, while connectional modularity in the LCIC gives rise to segregated input-output channels, local circuits provide the architecture for integration between these two streams. [ABSTRACT FROM AUTHOR]

Tumors protruding into the cerebral aqueduct are rare, and tumors arising from within the cerebral aqueduct are rarer still. In this report, we discuss the presentation and clinical outcome of a 65-year-old man who presented to us with symptoms of hydrocephalus. Prior imaging had revealed a small enhancing nodule within the cerebral aqueduct. In the 6 months between initial imaging and our seeing the patient, the tumor demonstrated substantial interval growth, so the patient was offered resection. The tumor was accessed using a sitting, supracerebellar, intracollicular approach, which allowed for gross total resection of the mass without complication. Histopathology later revealed the lesion to be a hemangioblastoma. Two years after surgery, the patient was doing well with no neurologic deficits. We report the first case of an aqueductal hemangioblastoma and describe our use of a sitting, supracerebellar, intracollicular approach to access tumors occupying this cerebrospinal fluid space. [ABSTRACT FROM AUTHOR]

Individuals aged 12–20 years drink 11% of all alcohol consumed in the United States with more than 90% consumed in the form of binge drinking. Early onset alcohol use is a strong predictor of future alcohol dependence. The study of the effects of excessive alcohol use on the human brain is hampered by limited information regarding the quantity and frequency of exposure to alcohol. Animal models can control for age at alcohol exposure onset and enable isolation of neural substrates of exposure to different patterns and quantities of ethanol (EtOH). As with humans, a frequently used binge exposure model is thought to produce dependence and affect predominantly corticolimbic brain regions. in vivo neuroimaging enables animals models to be examined longitudinally, allowing for each animal to serve as its own control. Accordingly, we conducted 3 magnetic resonance imaging (MRI) sessions (baseline, binge, recovery) to track structure throughout the brains of wild type Wistar rats to test the hypothesis that binge EtOH exposure affects specific brain regions in addition to corticolimbic circuitry. Voxel-based comparisons of 13 EtOH- vs. 12 water- exposed animals identified significant thalamic shrinkage and lateral ventricular enlargement as occurring with EtOH exposure, but recovering with a week of abstinence. By contrast, pretectal nuclei and superior and inferior colliculi shrank in response to binge EtOH treatment but did not recover with abstinence. These results identify brainstem structures that have been relatively underreported but are relevant for localizing neurocircuitry relevant to the dynamic course of alcoholism.

Acoustically evoked seizures (e.g., audiogenic seizures or AGS) are common in models of inherited epilepsy and occur in a variety of species including rat, mouse, and hamster. Two models that have been particularly well studied are the genetically epilepsy prone rat (GEPR-3) and the Wistar Audiogenic Rat (WAR) strains. Acute and repeated AGS, as well as comorbid conditions, displays a close phenotypic overlap in these models. Whether these similarities arise from convergent or divergent structural changes in the brain remains unknown. Here, we examined the brain structure of Sprague Dawley (SD) and Wistar (WIS) rats, and quantified changes in the GEPR-3 and WAR, respectively. Brains from adult, male rats of each strain (n = 8–10 per group) were collected, fixed, and embedded in agar and imaged using a 7 tesla Bruker MRI. Post-acquisition analysis included voxel-based morphometry (VBM), diffusion tensor imaging (DTI), and manual volumetric tracing. In the VBM analysis, GEPR-3 displayed volumetric changes in brainstem structures known to be engaged by AGS (e.g., superior and inferior colliculus, periaqueductal grey) and in forebrain structures (e.g., striatum, septum, nucleus accumbens). WAR displayed volumetric changes in superior colliculus, and a broader set of limbic regions (e.g., hippocampus, amygdala/piriform cortex). The only area of significant overlap in the two strains was the midline cerebellum: both GEPR-3 and WAR showed decreased volume compared to their control strains. In the DTI analysis, GEPR-3 displayed decreased fractional anisotropy (FA) in the corpus callosum, posterior commissure and commissure of the inferior colliculus (IC). WAR displayed increased FA only in the commissure of IC. These data provide a biological basis for further comparative and mechanistic studies in the GEPR-3 and WAR models, as well as provide additional insight into commonalities in the pathways underlying AGS susceptibility and behavioral comorbidity. [ABSTRACT FROM AUTHOR]

Descending projections from the thalamus and related structures to the midbrain are evolutionarily highly conserved. However, the basic organization of this auditory thalamotectal pathway has not yet been characterized. The purpose of this study was to obtain a better understanding of the anatomical and neurochemical features of this pathway. Analysis of the distributions of retrogradely labeled cells after focal injections of retrograde tracer into the inferior colliculus (IC) of the mouse revealed that most of the subcortical descending projections originated in the brachium of the IC and the paralaminar portions of the auditory thalamus. In addition, the vast majority of thalamotectal cells were found to be negative for the calcium-binding proteins calbindin, parvalbumin, or calretinin. Using two different strains of GAD-GFP mice, as well as immunostaining for GABA, we found that a subset of neurons in the brachium of the IC is GABAergic, suggesting that part of this descending pathway is inhibitory. Finally, dual retrograde injections into the IC and amygdala plus corpus striatum as well into the IC and auditory cortex did not reveal any double labeling. These data suggest that the thalamocollicular pathway comprises a unique population of thalamic neurons that do not contain typical calcium-binding proteins and do not project to other paralaminar thalamic forebrain targets, and that a previously undescribed descending GABAergic pathway emanates from the brachium of the IC. J. Comp. Neurol. 525:885-900, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

It is well established that spontaneous activity in the developing mammalian brain plays a fundamental role in setting up the precise connectivity found in mature sensory circuits. Experiments that produce abnormal activity or that systematically alter neural firing patterns during periods of circuit development strongly suggest that the specific patterns and the degree of correlation in firing may contribute in an instructive manner to circuit refinement. In fish and amphibians, unlike amniotic vertebrates, sensory input directly drives patterned activity during the period of initial projection outgrowth and innervation. Experiments combining sensory stimulation with live imaging, which can be performed non-invasively in these simple vertebrate models, have provided important insights into the mechanisms by which neurons read out and respond to activity patterns. This article reviews the classic and recent literature on spontaneous and evoked activity-dependent circuit refinement in sensory systems and formalizes a set of mechanistic rules for the transformation of patterned activity into accurate neuronal connectivity in the developing brain. [ABSTRACT FROM AUTHOR]

Listening conditions in the real world involve segregating the stimuli of interest from competing auditory stimuli that differ in their sound level and spectral content. It is in these conditions of complex spectro-temporal processing that listeners with age-related hearing loss experience the most difficulties. Envelope following responses (EFRs) provide objective neurophysiological measures of auditory processing. EFRs were obtained to two simultaneous sinusoidally amplitude modulated (sAM) tones from young and aged Fischer-344 rats. One was held at a fixed suprathreshold sound level (sAM1FL) while the second varied in sound level (sAM2VL) and carrier frequency. EFR amplitudes to sAM1FL in the young decreased with signal-to-noise ratio (SNR), and this reduction was more pronounced when the sAM2VL carrier frequency was spectrally separated from sAM1FL. Aged animals showed similar trends, while having decreased overall response amplitudes compared to the young. These results were replicated using an established computational model of the auditory nerve. The trends observed in the EFRs were shown to be due to the contributions of the low-frequency tails of high-frequency neurons, rather than neurons tuned to the sAM1FL carrier frequency. Modeling changes in threshold and neural loss reproduced some of the changes seen with age, but accuracy improved when combined with an additional decrease representing synaptic loss of auditory nerve neurons. Sound segregation in this case derives primarily from peripheral processing, regardless of age. Contributions by more central neural mechanisms are likely to occur only at low SNRs. [ABSTRACT FROM AUTHOR]

Prior studies have shown an ‘alternate antisaccade-goal bias’, in that the saccadic landing points of antisaccades were displaced towards the location of antisaccade goals used in other trials in the same experimental block. Thus the motor response in one trial induced a spatial bias of a motor response in another trial. In this study we investigated whether sensory information, i.e. the location of a visual stimulus, might have a spatial effect on a motor response too. Such an effect might be attractive as for the alternate antisaccade-goal bias or repulsive. For this purpose we used block of trials with either antisaccades, prosaccades or mixed trials in order to study the alternate-trial biases generated by antisaccade goals, antisaccade stimuli, and prosaccade goals. in contrast to the effects of alternate antisaccade goals described in prior studies, alternate antisaccade stimuli generated a significant repulsive bias of about 1.8°: furthermore, if stimulus and motor goal coincide, as with an alternate prosaccade, the repulsive effect of a stimulus prevails, causing a bias of about 0.9°. Taken together with prior results, these findings may reflect averaging of current and alternate trial activity in a salience map, with excitatory activity from the motor response and inhibitory activity from the sensory input..

Sensory events in the space around us trigger specific motor patterns directed toward or away from the spatial location of the sensory source. Spatially-defined sensorimotor associations are well-known in the visual domain but less so for the auditory modality. In particular no spatially-directed audio-motor association has been described for the upper limb. We tested the instantaneous directional tuning of the corticospinal system by means of single-pulse transcranial magnetic stimulation (TMS) over the left motor cortex in 16 healthy volunteers while at rest. We recorded the lateral accelerations of the TMS-evoked movement by means of an accelerometer placed on the forearm. Acoustic stimuli (pure tone frequency = 1000 Hz, duration = 50 ms) coming from 25 different directions lying in the axial anterior half-plane at the height of the participant’s ears were played on earphones. The entire set of sound directions covered a span of 160° (±80° where 0° is the frontal direction) at a fixed azimuth angle. Six different intervals between sound onset and TMS (0, 25, 50, 100, 150 and 200 ms) were tested for each sound direction. Significant correlations were found between sound origin and TMS-evoked arm accelerations only when TMS was delivered 50 ms prior to sound onset. We show the presence in the upper limb motor system of auditory spatial tuning. Sound information accesses the motor system at very short latency, potentially compatible with both a subcortical and a cortical origin of the response. The use of TMS-evoked accelerations allowed us to disclose a strict directional tuning in audio-motor associations. [ABSTRACT FROM AUTHOR]

Hearing thresholds and wave amplitudes measured using auditory brainstem responses (ABRs) to brief sounds are the predominantly used clinical measures to objectively assess auditory function. However, frequency-following responses (FFRs) to tonal carriers and to the modulation envelope (envelope-following responses or EFRs) to longer and spectro-temporally modulated stimuli are rapidly gaining prominence as a measure of complex sound processing in the brainstem and midbrain. In spite of numerous studies reporting changes in hearing thresholds, ABR wave amplitudes, and the FFRs and EFRs under neurodegenerative conditions, including aging, the relationships between these metrics are not clearly understood. In this study, the relationships between ABR thresholds, ABR wave amplitudes, and EFRs are explored in a rodent model of aging. ABRs to broadband click stimuli and EFRs to sinusoidally amplitude-modulated noise carriers were measured in young (3-6 months) and aged (22-25 months) Fischer-344 rats. ABR thresholds and amplitudes of the different waves as well as phase-locking amplitudes of EFRs were calculated. Age-related differences were observed in all these measures, primarily as increases in ABR thresholds and decreases in ABR wave amplitudes and EFR phase-locking capacity. There were no observed correlations between the ABR thresholds and the ABR wave amplitudes. Significant correlations between the EFR amplitudes and ABR wave amplitudes were observed across a range of modulation frequencies in the young. However, no such significant correlations were found in the aged. The aged click ABR amplitudes were found to be lower than would be predicted using a linear regression model of the young, suggesting altered gain mechanisms in the relationship between ABRs and FFRs with age. These results suggest that ABR thresholds, ABR wave amplitudes, and EFRs measure complementary aspects of overlapping neurophysiological processes and the relationships between these measurements changes asymmetrically with age. Hence, measuring all three metrics provides a more complete assessment of auditory function, especially under pathological conditions like aging. [ABSTRACT FROM AUTHOR]

The capacity to select the most important information and suppress distracting information is crucial for survival. The midbrain contains a network critical for the selection of the strongest stimulus for gaze and attention. In avians, the optic tectum (OT; called the superior colliculus in mammals) and the GABAergic nucleus isthmi pars magnocellularis (Imc) cooperate in the selection process. In the chicken, OT layer 10, located in intermediate layers, responds to afferent input with gamma periodicity (25-75 Hz), measured at the level of individual neurons and the local field potential. In contrast, Imc neurons, which receive excitatory input from layer 10 neurons, respond with tonic, unusually high discharge rates (>150 spikes/s). In this study, we reveal the source of this high-rate inhibitory activity: layer 10 neurons that project to the Imc possess specialized biophysical properties that enable them to transform afferent drive into high firing rates (~130 spikes/s), whereas neighboring layer 10 neurons, which project elsewhere, transform afferent drive into lower-frequency, periodic discharge patterns. Thus, the intermediate layers of the OT contain parallel, intercalated microcircuits that generate different temporal patterns of activity linked to the functions of their respective downstream targets. [ABSTRACT FROM AUTHOR]

Detecting and locating environmental events are markedly enhanced by the midbrain's ability to integrate visual and auditory cues. Its capacity for multisensory integration develops in cats 1- 4 months after birth but only after acquiring extensive visual-auditory experience. However, briefly deactivating specific regions of association cortex during this period induced long-term disruption of this maturational process, such that even 1 year later animals were unable to integrate visual and auditory cues to enhance their behavioral performance. The data from this animal model reveal a window of sensitivity within which association cortex mediates the encoding of cross-modal experience in the midbrain. Surprisingly, however, 3 years later, and without any additional intervention, the capacity appeared fully developed. This suggests that, although sensitivity degrades with age, the potential for acquiring or modifying multisensory integration capabilities extends well into adulthood. [ABSTRACT FROM AUTHOR]

Our knowledge of age related changes in auditory processing in the central auditory system is limited, unlike the changes in the peripheral hearing organs which are more extensively studied. This study aims to further understanding of temporal processing in aging using non-invasive electrophysiological measurements in a rat model system. Amplitude modulation following responses (AMFRs) were assessed using sinusoidally amplitude modulated (SAM) tones presented to aged (92-95 weeks old) and young (9-12 weeks old) Fischer-344 rats. The modulation frequency and sound level were systematically varied, and the SAM stimuli were also presented simultaneously with wide-band background noise at various levels. The overall shapes and cutoff frequencies of the AMFR temporal modulation transfer functions (tMTFs) were similar between young and aged animals. The fast Fourier transform (FFT) amplitudes of the aged animals were similar to the young in the 181Hz-512Hz modulation frequency range, but were significantly lower at most modulation frequencies above and below. There were no significant age related differences in the nature of growth or FFT amplitudes with change in sound level at 256Hz and 1024Hz modulation frequencies. The AMFR amplitudes were also not correlated with the ABR wave I or wave III amplitudes elicited for broadband click stimuli presented at the same sound level suggesting that sustained AMFR responses provide complementary information to phasic ABR responses. The FFT amplitudes varied significantly between young and aged animals for SAM stimuli in the presence of background noise, depending on the modulation frequency used and signal to noise ratio. The results show that the representation of temporally modulated stimuli is similar between young and aged animals in quiet listening conditions, but diverges substantially with the addition of background noise. This is consistent with a decrease in inhibition causing altered temporal processing with age.

Chronic neural recordings were taken from the midbrain superior colliculus (SC) of echolocating bats while they were engaged in one of two distinct behavioral tasks: virtual target amplitude discrimination (VTAD) and real oscillating target tracking (ROTT). In the VTAD task, bats used a limited range of sonar call features to discriminate the amplitude category of echoes, whereas in the ROTT task, the bat produced dynamically modulated sonar calls to track a moving target. Newly developed methods for chronic recordings in unrestrained, behaving bats reveal two consistent bouts of SC neural activity preceding the onset of sonar vocalizations in both tasks. A short lead bout occurs tightly coupled to vocal onset (VTAD, -5.1 to -2.2 ms range, -3.6 ± 0.7 ms mean lead time; ROTT, -3.0 to -0.4 ms range, -1.2 ± 1.3 ms mean lead time), and this activity may play a role in marking the time of each sonar emission. Along lead bout in SC activity occurs earlier and spreads over a longer interval (VTAD, -40.6 to -8.4 ms range, -22.2 ± 3.9 ms mean lead time; ROTT, -29.8 to -7.1 ms range, -17.5 ± 9.1 ms mean lead time) when compared with short lead events. In the goal-directed ROTT task, the timing of long lead event times vary with the bat's sonar call duration. This finding, along with behavioral studies demonstrating that bats adjust sonar call duration as they track targets at changing distance, suggests the bat SC contributes to range-dependent adjustments of sonar call duration. [ABSTRACT FROM AUTHOR]

Abstract: The midbrain is essential for prepulse inhibition (PPI) of the startle reflex, but the exact neural circuits for PPI are not yet determined. Electrical stimulation of the superior colliculus (SC) or pedunculopontine tegmentum was used to characterize the neurons and pathways that mediate PPI and the activation of startle that also occurs at higher currents in the same sites. Startle was inhibited by prepulses in most, but not all SC sites, with the lowest intensity sites in intermediate layers of SC. PPI latencies in SC sites were 4–6 ms longer than in inferior colliculus, intercollicular nucleus or pedunculopontine sites. Contrary to previous serial models, there must be two parallel midbrain pathways for PPI, a faster auditory pathway from inferior colliculus to pedunculopontine tegmentum, and a slower multimodal SC output for PPI. Double-pulse stimulation of SC sites shows that PPI results from direct stimulation of neurons with moderate refractory periods (0.4–1.0 ms), similar to SC neurons that mediate contraversive turning responses. By contrast, startle activation occurring at higher currents in all SC sites (even sites where PPI could not be elicited) results from stimulation of very short refractory period neurons (0.3–0.5 ms) and very long refractory period neurons (1.0–2.0 ms), with startle inhibition often found from 0.5–1.0 ms. Startle activation appears to result from stimulation of short refractory period neurons in deep SC layers that mediate fear-potentiated startle, plus long refractory period substrates in more dorsal SC sites. [Copyright &y& Elsevier]

It is known that the saccadic system shows adaptive changes when the command sent to the extraocular muscles is inappropriate. Despite an abundance of supportive psychophysical investigations, the neurophysiological substrate of this process is still debated. The present study addresses this issue using H215O positron emission tomography (PET). We contrasted three conditions in which healthy human subjects were required to perform saccadic eye movements toward peripheral visual targets. Two conditions involved a modification of the target location during the course of the initial saccade, when there is suppression of visual perception. In the RAND condition, intra-saccadic target displacement was random from trial-to-trial, precluding any systematic modification of the primary saccade amplitude. In the ADAPT condition, intra-saccadic target displacement was uniform, causing adaptive modification of the primary saccade amplitude. In the third condition (stationary, STAT), the target remained at the same location during the entire trial. Difference images reflecting regional cerebral-blood-flow changes attributable to the process of saccadic adaptation (ADAPT minus RAND; ADAPT minus STAT) showed a selective activation in the oculomotor cerebellar vermis (OCV; lobules VI and VII). This finding is consistent with neurophysiological studies in monkeys. Additional analyses indicated that the cerebellar activation was not related to kinematic factors, and that the absence of significant activation within the frontal eye fields (FEF) or the superior colliculus (SC) did not represent a false negative inference. Besides the contribution of the OCV to saccadic adaptation, we also observed, in the RAND condition, that the saccade amplitude was significantly larger when the previous trial involved a forward jump than when the previous trial involved a backward jump. This observation indicates that saccade accuracy is constantly monitored on a trial-to-trial basis. Behavioral measurements and PET observations (RAND minus STAT) suggest that this single-trial control of saccade amplitude may be functionally distinct from the process of saccadic adaptation. [ABSTRACT FROM AUTHOR]

Higher-order (HO) thalamic nuclei interact extensively and reciprocally with the cerebral cortex. These corticothalamic (CT) interactions are thought to be important for sensation and perception, attention, and many other important brain functions. CT projections to HO thalamic nuclei, such as the visual pulvinar, originate from two different excitatory populations in cortical layers 5 and 6, whereas first-order nuclei (such as the dorsolateral geniculate nucleus; dLGN) only receive layer 6 CT input. It has been proposed that these layer 5 and layer 6 CT pathways have different functional influences on the HO thalamus, but this has never been directly tested. By optogenetically inactivating different CT populations in the primary visual cortex (V1) and recording single-unit activity from V1, dLGN, and pulvinar of awake mice, we demonstrate that layer 5, but not layer 6, CT projections drive visual responses in the pulvinar, even while both pathways provide retinotopic, baseline excitation to their thalamic targets. Inactivating the superior colliculus also suppressed visual responses in the same subregion of the pulvinar, demonstrating that cortical layer 5 and subcortical inputs both contribute to HO visual thalamic activity—even at the level of putative single neurons. Altogether, these results indicate a functional division of "driver" and "modulator" CT pathways from V1 to the visual thalamus in vivo. [Display omitted] • Corticothalamic neurons (CTs) in layer 5 or 6 of V1 were inactivated in awake mice • Layer 5 (L5), but not layer 6 (L6), CTs "drive" visual responses in the pulvinar • Both CT projection pathways to the visual thalamus are retinotopically organized • Driving inputs from L5 CTs and the superior colliculus converge in the lateral pulvinar Kirchgessner et al. find that inactivating corticothalamic (CT) neurons in layer 5, but not layer 6, of the mouse visual cortex suppresses visual responses in the pulvinar, indicating a "driving" versus "modulatory" distinction between CT populations. Layer 5 drivers converge with subcortical (superior colliculus) driving inputs in the pulvinar. [ABSTRACT FROM AUTHOR]

Hemianopia induced by unilateral visual cortex lesions can be resolved by repeatedly exposing the blinded hemifield to auditory-visual stimuli. This rehabilitative "training" paradigm depends on mechanisms of multisensory plasticity that restore the lost visual responsiveness of multisensory neurons in the ipsilesional superior colliculus (SC) so that they can once again support vision in the blinded hemifield. These changes are thought to operate via the convergent visual and auditory signals relayed to the SC from association cortex (the anterior ectosylvian sulcus [AES], in cat). The present study tested this assumption by cryogenically deactivating ipsilesional AES in hemianopic, anesthetized cats during weekly multisensory training sessions. No signs of visual recovery were evident in this condition, even after providing animals with up to twice the number of training sessions required for effective rehabilitation. Subsequent training under the same conditions, but with AES active, reversed the hemianopia within the normal timeframe. These results indicate that the corticotectal circuit that is normally engaged in SC multisensory plasticity has to be operational for the brain to use visual-auditory experience to resolve hemianopia., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Visual stimuli can evoke complex behavioral responses, but the underlying streams of neural activity in mammalian brains are difficult to follow because of their size. Here, I review the visual system of zebrafish larvae, highlighting where recent experimental evidence has localized the functional steps of visuomotor transformations to specific brain areas. The retina of a larva encodes behaviorally relevant visual information in neural activity distributed across feature-selective ganglion cells such that signals representing distinct stimulus properties arrive in different areas or layers of the brain. Motor centers in the hindbrain encode motor variables that are precisely tuned to behavioral needs within a given stimulus setting. Owing to rapid technological progress, larval zebrafish provide unique opportunities for obtaining a comprehensive understanding of the intermediate processing steps occurring between visual and motor centers, revealing how visuomotor transformations are implemented in a vertebrate brain.

Individuals aged 12-20 years drink 11% of all alcohol consumed in the United States with more than 90% consumed in the form of binge drinking. Early onset alcohol use is a strong predictor of future alcohol dependence. The study of the effects of excessive alcohol use on the human brain is hampered by limited information regarding the quantity and frequency of exposure to alcohol. Animal models can control for age at alcohol exposure onset and enable isolation of neural substrates of exposure to different patterns and quantities of ethanol (EtOH). As with humans, a frequently used binge exposure model is thought to produce dependence and affect predominantly corticolimbic brain regions. in vivo neuroimaging enables animals models to be examined longitudinally, allowing for each animal to serve as its own control. Accordingly, we conducted 3 magnetic resonance imaging (MRI) sessions (baseline, binge, recovery) to track structure throughout the brains of wild type Wistar rats to test the hypothesis that binge EtOH exposure affects specific brain regions in addition to corticolimbic circuitry. Voxel-based comparisons of 13 EtOH- vs. 12 water- exposed animals identified significant thalamic shrinkage and lateral ventricular enlargement as occurring with EtOH exposure, but recovering with a week of abstinence. By contrast, pretectal nuclei and superior and inferior colliculi shrank in response to binge EtOH treatment but did not recover with abstinence. These results identify brainstem structures that have been relatively underreported but are relevant for localizing neurocircuitry relevant to the dynamic course of alcoholism.

Listening conditions in the real world involve segregating the stimuli of interest from competing auditory stimuli that differ in their sound level and spectral content. It is in these conditions of complex spectro-temporal processing that listeners with age-related hearing loss experience the most difficulties. Envelope following responses (EFRs) provide objective neurophysiological measures of auditory processing. EFRs were obtained to two simultaneous sinusoidally amplitude modulated (sAM) tones from young and aged Fischer-344 rats. One was held at a fixed suprathreshold sound level (sAM1FL) while the second varied in sound level (sAM2VL) and carrier frequency. EFR amplitudes to sAM1FL in the young decreased with signal-to-noise ratio (SNR), and this reduction was more pronounced when the sAM2VL carrier frequency was spectrally separated from sAM1FL. Aged animals showed similar trends, while having decreased overall response amplitudes compared to the young. These results were replicated using an established computational model of the auditory nerve. The trends observed in the EFRs were shown to be due to the contributions of the low-frequency tails of high-frequency neurons, rather than neurons tuned to the sAM1FL carrier frequency. Modeling changes in threshold and neural loss reproduced some of the changes seen with age, but accuracy improved when combined with an additional decrease representing synaptic loss of auditory nerve neurons. Sound segregation in this case derives primarily from peripheral processing, regardless of age. Contributions by more central neural mechanisms are likely to occur only at low SNRs.

The capacity to select the most important information and suppress distracting information is crucial for survival. The midbrain contains a network critical for the selection of the strongest stimulus for gaze and attention. In avians, the optic tectum (OT; called the superior colliculus in mammals) and the GABAergic nucleus isthmi pars magnocellularis (Imc) cooperate in the selection process. In the chicken, OT layer 10, located in intermediate layers, responds to afferent input with gamma periodicity (25-75 Hz), measured at the level of individual neurons and the local field potential. In contrast, Imc neurons, which receive excitatory input from layer 10 neurons, respond with tonic, unusually high discharge rates (>150 spikes/s). In this study, we reveal the source of this high-rate inhibitory activity: layer 10 neurons that project to the Imc possess specialized biophysical properties that enable them to transform afferent drive into high firing rates (~130 spikes/s), whereas neighboring layer 10 neurons, which project elsewhere, transform afferent drive into lower-frequency, periodic discharge patterns. Thus, the intermediate layers of the OT contain parallel, intercalated microcircuits that generate different temporal patterns of activity linked to the functions of their respective downstream targets., (Copyright © 2014 the authors 0270-6474/14/348130-09$15.00/0.)

The inferior colliculus (IC) is a major center for integration of auditory information as it receives ascending projections from a variety of brainstem nuclei as well as descending projections from the thalamus and auditory cortex. The ascending projections are both excitatory and inhibitory and their convergence at the IC results in a microcircuitry that is important for shaping responses to simple, binaural, and modulated sounds in the IC. Here, we examined the role inhibition plays in shaping selectivity to vocalizations in the IC of awake, normal-hearing adult mice (CBA/CaJ strain). Neurons in the IC of mice show selectivity in their responses to vocalizations, and we hypothesized that this selectivity is created by inhibitory microcircuitry in the IC. We compared single unit responses in the IC to pure tones and a variety of ultrasonic mouse vocalizations before and after iontophoretic application of GABA(A) receptor (GABA(A)R) and glycine receptor (GlyR) antagonists. The most pronounced effects of blocking GABA(A)R and GlyR on IC neurons were to increase spike rates and broaden excitatory frequency tuning curves in response to pure tone stimuli, and to decrease selectivity to vocalizations. Thus, inhibition plays an important role in creating selectivity to vocalizations in the IC.

To investigate why the development of a completely circular striated sphincter is so rare, we examined histological sections of 11 female and 11 male mid-term human fetuses. In male fetuses, the striated muscle initially extended in the frontal, rather than in the horizontal plane. However, a knee-like portion was absent in the female fetal urethra because, on the inferior side of the vaginal end, a wide groove for the future vestibule opened inferiorly. Accordingly, it was difficult for the developing striated muscle to surround the groove, even though there was not a great difference in width or thickness between the female vestibule and the male urethra. The development of a completely circular striated sphincter seems to be impossible in females because of interruption of the frontal plane by the groove-like vestibule. However, we cannot rule out the possibility that before descent of the vagina, the urethral striated muscle extends posteriorly.

Our knowledge of age-related changes in auditory processing in the central auditory system is limited, unlike the changes in the peripheral hearing organs which are more extensively studied. This study aims to further understanding of temporal processing in aging using non-invasive electrophysiological measurements in a rat model system. Amplitude modulation following responses (AMFRs) were assessed using sinusoidally amplitude modulated (SAM) tones presented to aged (92- to 95-weeks old) and young (9- to 12-weeks old) Fischer-344 rats. The modulation frequency and sound level were systematically varied, and the SAM stimuli were also presented simultaneously with wideband background noise at various levels. The overall shapes and cutoff frequencies of the AMFR temporal modulation transfer functions (tMTFs) were similar between young and aged animals. The fast Fourier transform (FFT) amplitudes of the aged animals were similar to the young in the 181-512 Hz modulation frequency range, but were significantly lower at most modulation frequencies above and below. There were no significant age-related differences in the nature of growth or FFT amplitudes with change in sound level at 256 and 1024 Hz modulation frequencies. The AMFR amplitudes were also not correlated with the ABR wave I or wave III amplitudes elicited for broadband click stimuli presented at the same sound level suggesting that sustained AMFR provide complementary information to phasic ABR responses. The FFT amplitudes varied significantly between young and aged animals for SAM stimuli in the presence of background noise, depending on the modulation frequency used and signal to noise ratio. The results show that the representation of temporally modulated stimuli is similar between young and aged animals in quiet listening conditions, but diverges substantially with the addition of background noise. This is consistent with a decrease in inhibition causing altered temporal processing with age.