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The striatum serves an important role in motor control, and neurons in this area encode the body's initiation, cessation, and speed of locomotion. However, it remains unclear whether the same neurons also encode the step-by-step rhythmic motor patterns of individual limbs that characterize gait. By combining high-speed video tracking, electrophysiology, and optogenetic tagging, we found that a sizable population of both D1 and D2 receptor expressing medium spiny projection neurons (MSNs) were phase-locked to the gait cycle of individual limbs in mice. Healthy animals showed balanced limb phase-locking between D1 and D2 MSNs, while dopamine depletion led to stronger phase-locking in D2 MSNs. These findings indicate that striatal neurons represent gait on a single-limb and step basis, and suggest that elevated limb phase-locking of D2 MSNs may underlie some of the gait impairments associated with dopamine loss.

To better understand neural processing during adaptive learning of stimulus‐response‐reward contingencies, we recorded synchrony of neuronal activity in anterior cingulate cortex (ACC) and hippocampal rhythms in male rats acquiring and switching between spatial and visual discrimination tasks in a Y‐maze. ACC population activity as well as single unit activity shifted shortly after task rule changes or just before the rats adopted different task strategies. Hippocampal theta oscillations (associated with memory encoding) modulated an elevated proportion of rule‐change responsive neurons (70%), but other neurons that were correlated with strategy‐change, strategy value and reward‐rate were not. However, hippocampal sharp wave‐ripples modulated significantly higher proportions of rule‐change, strategy‐change and reward‐rate responsive cells during post‐session sleep but not pre‐session sleep. This suggests an underestimated mechanism for hippocampal mismatch and contextual signals to facilitate ACC to detect contingency changes for cognitive flexibility, a function that is attenuated after it is damaged. [ABSTRACT FROM AUTHOR]

The striatum serves an important role in motor control, and neurons in this area encode the body’s initiation, cessation, and speed of locomotion. However, it remains unclear whether the same neurons also encode the step-by-step rhythmic motor patterns of individual limbs that characterize gait. By combining high-speed video tracking, electrophysiology, and optogenetic tagging, we found that a sizable population of both D1 and D2 receptor expressing medium spiny projection neurons (MSNs) were phase-locked to the gait cycle of individual limbs in mice. Healthy animals showed balanced limb phase-locking between D1 and D2 MSNs, while dopamine depletion led to stronger phase-locking in D2 MSNs. These findings indicate that striatal neurons represent gait on a single-limb and step basis, and suggest that elevated limb phase-locking of D2 MSNs may underlie some of the gait impairments associated with dopamine loss.

The receptive field of many visual neurons is composed of a central responsive area, the classical receptive field, and a non‐classical receptive field, also called the "suppressive surround." A visual stimulus placed in the suppressive surround does not induce any response but modulates visual responses to stimuli within the classical receptive field, usually by suppressing them. Therefore, visual responses become smaller when stimuli exceed the classical receptive field size. The stimulus size inducing the maximal response is called the preferred stimulus size. In cortex, there is good correspondence between the sizes of the classical receptive field and the preferred stimulus. In contrast, in the rodent superior colliculus, the preferred size is often several fold smaller than the classical receptive field size. Here, we show that in the rat superior colliculus, the preferred stimulus size changes as a square root of the contrast inverse and the classical receptive field size is independent of contrast. In addition, responses to annulus were largely independent of the inner hole size. To explain these data, three models were tested: the divisive modulation of the gain by the suppressive surround (the "normalization" model), the difference of the Gaussians, and a divisive model that incorporates saturation to light flux. Despite the same number of free parameters, the model incorporating saturation to light performed the best. Thus, our data indicate that in rats, the saturation to light can be a dominant phenomenon even at relatively low illumination levels defining visual responses in the collicular neurons. [ABSTRACT FROM AUTHOR]

The meaning behind neural single unit activity has constantly been a challenge, so it will persist in the foreseeable future. As one of the most sourced strategies, detecting neural activity in high-resolution neural sensor recordings and then attributing them to their corresponding source neurons correctly, namely the process of spike sorting, has been prevailing so far. Support from ever-improving recording techniques and sophisticated algorithms for extracting worthwhile information and abundance in clustering procedures turned spike sorting into an indispensable tool in electrophysiological analysis. This review attempts to illustrate that in all stages of spike sorting algorithms, the past 5 years innovations' brought about concepts, results, and questions worth sharing with even the non-expert user community. By thoroughly inspecting latest innovations in the field of neural sensors, recording procedures, and various spike sorting strategies, a skeletonization of relevant knowledge lays here, with an initiative to get one step closer to the original objective: deciphering and building in the sense of neural transcript. [ABSTRACT FROM AUTHOR]

The meaning behind neural single unit activity has constantly been a challenge, so it will persist in the foreseeable future. As one of the most sourced strategies, detecting neural activity in high-resolution neural sensor recordings and then attributing them to their corresponding source neurons correctly, namely the process of spike sorting, has been prevailing so far. Support from ever-improving recording techniques and sophisticated algorithms for extracting worthwhile information and abundance in clustering procedures turned spike sorting into an indispensable tool in electrophysiological analysis. This review attempts to illustrate that in all stages of spike sorting algorithms, the past 5 years innovations' brought about concepts, results, and questions worth sharing with even the non-expert user community. By thoroughly inspecting latest innovations in the field of neural sensors, recording procedures, and various spike sorting strategies, a skeletonization of relevant knowledge lays here, with an initiative to get one step closer to the original objective: deciphering and building in the sense of neural transcript.

AimElectrodes that provide brain to machine or computer interfacing must survive the lifetime of the person to be considered an acceptable prosthetic. The electrodes may be external such as with electroencephalographic (EEG), internal extracortical such as electrocorticographic (ECoG) or intracortical.MethodsMost intracortical electrodes are placed close to the neuropil being recorded and do not survive years of recording. However, the Neurotrophic Electrode is placed within the cortex and the neuropil grows inside and through the hollow tip of the electrode and is thus trapped inside. Highly flexible coiled lead wires minimize the strain on the electrode tip. Histological analysis includes immunohistochemical detection of neurofilaments and the absence of gliosis.ResultsThis configuration led to a decade long recording in this locked-in person. At year nine, the neural activity underwent conditioning experiments indicating that the neural activity was functional and not noise. This paper presents data on the histological analysis of the tissue inside the electrode tip after 13 years of implantation.ConclusionThis paper is a singular example of histological analysis after a decade of recording. The histological analysis laid out herein is strong evidence that the brain can grow neurites into the electrode tip and record for a decade. This is profoundly important in the field of brain to machine or computer interfacing by implying that long term electrodes should incorporate some means of growing the neuropil into the electrode rather than placing the electrode into the neuropil.

• Durations can be encoded in various patterns of single unit activity. • Population activity and communication between brain areas can also encode durations. • Combination of unit and population activity may be the basis of our internal clock. • Experiments designed to study the neural basis of interval timing are needed. The processing of temporal intervals is essential to create causal maps and to predict future events so as to best adapt one's behavior. In this review, we explore the different brain activity patterns associated with processing durations and expressing temporally-adapted behavior in animals. We begin by describing succinctly some of the current models of the internal clock that can orient us in what to look for in brain activity. We then outline how durations can be decoded by single cell activity and which activity patterns could be associated with interval timing. We further point to similar patterns that have been observed at a more global level within brain areas (e.g. local field potentials) or, even, between these areas, that could represent another way of encoding duration or could constitute a necessary part for more complex temporal processing. Finally, we discuss to what extent neural data fit with internal clock models, and highlight improvements for experiments to obtain a more in-depth understanding of the brain's temporal encoding and processing. [ABSTRACT FROM AUTHOR]

Aim: Electrodes that provide brain to machine or computer interfacing must survive the lifetime of the person to be considered an acceptable prosthetic. The electrodes may be external such as with electroencephalographic (EEG), internal extracortical such as electrocorticographic (ECoG) or intracortical. Methods: Most intracortical electrodes are placed close to the neuropil being recorded and do not survive years of recording. However, the Neurotrophic Electrode is placed within the cortex and the neuropil grows inside and through the hollow tip of the electrode and is thus trapped inside. Highly flexible coiled lead wires minimize the strain on the electrode tip. Histological analysis includes immunohistochemical detection of neurofilaments and the absence of gliosis. Results: This configuration led to a decade long recording in this locked-in person. At year nine, the neural activity underwent conditioning experiments indicating that the neural activity was functional and not noise. This paper presents data on the histological analysis of the tissue inside the electrode tip after 13 years of implantation. Conclusion: This paper is a singular example of histological analysis after a decade of recording. The histological analysis laid out herein is strong evidence that the brain can grow neurites into the electrode tip and record for a decade. This is profoundly important in the field of brain to machine or computer interfacing by implying that long term electrodes should incorporate some means of growing the neuropil into the electrode rather than placing the electrode into the neuropil. [ABSTRACT FROM AUTHOR]

Objective . Our goal is to decode firing patterns of single neurons in the left ventralis intermediate nucleus (Vim) of the thalamus, related to speech production, perception, and imagery. For realistic speech brain-machine interfaces (BMIs), we aim to characterize the amount of thalamic neurons necessary for high accuracy decoding. Approach . We intraoperatively recorded single neuron activity in the left Vim of eight neurosurgical patients undergoing implantation of deep brain stimulator or RF lesioning during production, perception and imagery of the five monophthongal vowel sounds. We utilized the Spade decoder, a machine learning algorithm that dynamically learns specific features of firing patterns and is based on sparse decomposition of the high dimensional feature space. Main results . Spade outperformed all algorithms compared with, for all three aspects of speech: production, perception and imagery, and obtained accuracies of 100%, 96%, and 92%, respectively (chance level: 20%) based on pooling together neurons across all patients. The accuracy was logarithmic in the amount of neurons for all three aspects of speech. Regardless of the amount of units employed, production gained highest accuracies, whereas perception and imagery equated with each other. Significance . Our research renders single neuron activity in the left Vim a promising source of inputs to BMIs for restoration of speech faculties for locked-in patients or patients with anarthria or dysarthria to allow them to communicate again. Our characterization of how many neurons are necessary to achieve a certain decoding accuracy is of utmost importance for planning BMI implantation., (Creative Commons Attribution license.)

Much is known about the neural circuits of conditioned fear and its relevance to understanding anxiety disorders, but less is known about other anxiety-related behaviors such as active avoidance. Using a tone-signaled, platform-mediated avoidance task, we observed that pharmacological inactivation of the prelimbic prefrontal cortex (PL) delayed avoidance. Surprisingly, optogenetic silencing of PL glutamatergic neurons did not delay avoidance. Consistent with this, inhibitory but not excitatory responses of rostral PL neurons were associated with avoidance training. To test the importance of these inhibitory responses, we optogenetically stimulated PL neurons to counteract the tone-elicited reduction in firing rate. Photoactivation of rostral (but not caudal) PL neurons at 4 Hz impaired avoidance. These findings suggest that inhibitory responses of rostral PL neurons signal the avoidability of a potential threat and underscore the importance of designing behavioral optogenetic studies based on neuronal firing responses.

Abstract A 'pattern alternation paradigm' has been previously used in human ERP recordings to investigate the brain encoding of complex auditory regularities, but prior studies on regularity encoding in animal models to examine mechanisms of adaptation of auditory neuronal responses have used primarily oddball stimulus sequences to study stimulus-specific adaptation alone. In order to examine the sensitivity of neuronal adaptation to expected and unexpected events embedded in a complex sound sequence, we used a similar patterned sequence of sounds. We recorded single unit activity and compared neuronal responses in the rat inferior colliculus (IC) to sound stimuli conforming to pattern alternation regularity with those to stimuli in which occasional sound repetitions violated that alternation. Results show that some neurons in the rat inferior colliculus are sensitive to the history of patterned stimulation and to violations of patterned regularity, demonstrating that there is a population of subcortical neurons, located as early as the level of the midbrain, that can detect more complex stimulus regularities than previously supposed and that are as sensitive to complex statistics as some neurons in primary auditory cortex. Our findings indicate that these pattern-sensitive neurons can extract temporal and spectral regularities between successive acoustic stimuli. This is important because the extraction of regularities from the sound sequences will result in the development of expectancies for future sounds and hence, the present results are compatible with predictive coding models. Our results demonstrate that some collicular neurons, located as early as in the midbrain level, are involved in the generation and shaping of prediction errors in ways not previously considered and thus, the present findings challenge the prevailing view that perceptual organization of sound only emerges at the auditory cortex level. Highlights • Auditory midbrain, i.e., IC neurons are sensitive to complex statistics. • IC neurons are sensitive to stimulation history and violations of patterned regularity. • IC neurons extract spectral and temporal regularities between successive stimuli. • Results are consistent with a hierarchical model of predictive coding. [ABSTRACT FROM AUTHOR]

Background Sub-anesthetic doses of the non-competitive N -methyl- d -aspartate receptor (NMDA-R) antagonist ketamine evoke transient psychotomimetic effects, followed by persistent antidepressant effects in treatment-resistant depressed patients and rodents through still poorly understood mechanisms. Since phencyclidine (PCP) disinhibits thalamo-cortical networks by blocking NMDA-Rs on GABAergic neurons of the reticular thalamic nucleus (RtN), we examined ketamine's actions in the same areas. Methods Single units and local field potentials were recorded in chloral hydrate anesthetized male Wistar rats. The effects of cumulative ketamine doses (0.25–5 mg/kg, i.v.) on neuronal discharge and oscillatory activity were examined in RtN, mediodorsal and centromedial (MD/CM) thalamic nuclei, and layer VI of the medial prefrontal cortex (mPFC). Results Ketamine (1, 2 and 5 mg/kg, i.v.) significantly decreased the discharge of MD/CM, RtN and layer VI mPFC pyramidal neurons. Simultaneously, ketamine decreased the power of low frequency oscillations in all areas examined and increased gamma oscillations in mPFC and MD/CM. Lower ketamine doses (0.25 and 0.5 mg/kg, i.v.) were ineffective. Conclusions As observed for PCP, ketamine markedly inhibited the activity of RtN neurons. However, unlike PCP, this effect did not translate into a disinhibition of MD/CM and mPFC excitatory neurons, possibly due to a more potent and simultaneous blockade of NMDA-Rs by ketamine in MD/CM and mPFC neurons. Hence, the present in vivo results show that ketamine evokes an early transient inhibition of neuronal discharge in thalamo-cortical networks, following its rapid pharmacokinetics, which is likely associated to its psychotomimetic effects. The prolonged increase in gamma oscillations may underlie its antidepressant action. [ABSTRACT FROM AUTHOR]

Pain serves an important protective role. However, it can also have debilitating adverse effects if dysfunctional, such as in pathological pain conditions. As part of the thalamocortical circuit, the thalamic reticular nucleus (TRN) has been implicated to have important roles in controlling nociceptive signal transmission. However studies on how TRN neurons, especially how TRN neuronal subtypes categorized by temporal bursting firing patterns—typical bursting, atypical bursting, and non-bursting TRN neurons—contribute to nociceptive signal modulation is not known. To reveal the relationship between TRN neuronal subtypes and modulation of nociception, we simultaneously recorded behavioral responses and TRN neuronal activity to formalin induced nociception in freely moving mice. We found that typical bursting TRN neurons had the most robust response to nociception; changes in tonic firing rate of typical TRN neurons exactly matched changes in behavioral nociceptive responses, and burst firing rate of these neurons increased significantly when behavioral nociceptive responses were reduced. This implies that typical TRN neurons could critically modulate ascending nociceptive signals. The role of other TRN neuronal subtypes was less clear; atypical bursting TRN neurons decreased tonic firing rate after the second peak of behavioral nociception and the firing rate of non-bursting TRN neurons mostly remained at baseline level. Overall, our results suggest that different TRN neuronal subtypes contribute differentially to processing formalin induced sustained nociception in freely moving mice.

It is well known that epileptogenesis is associated with widespread neuronal network changes in brain regions adjacent to the seizure focus but also in remote structures including basal ganglia. Besides the superior colliculus, the pedunculopontine tegmental nucleus (PPN) is one of three main target regions of basal ganglia output activity and is reciprocally connected with the substantia nigra pars reticulata (SNr), which is critically involved in seizure propagation and manipulation. We here tested the hypothesis if, apart from the traditional view that the superior colliculus mediates seizure-gating mechanisms of the SNr, the PPN is involved in kindling-induced network changes. Rats were electrically kindled via the ipsilateral basolateral amygdala. In vivo extracellular single unit recordings of right PPN neurons were performed in kindled rats 1 day after a generalized seizure in order to examine kindling-associated rather than seizure-associated activity changes. The main findings of the study were (1) a seizure-outlasting drastically reduced firing rate of PPN neurons and (2) an increase in burst and irregular firing pattern in kindled rats compared with sham-kindled and naïve controls. These changes are likely to be caused by an altered inhibitory input from the SNr. Furthermore, kindling caused (3) the oscillation frequency of PPN neurons to shift towards lower frequencies. The kindling-induced activity changes were found to be anatomically restricted to the PPN, indicating that network changes follow distinct anatomical routes. We demonstrated that the PPN is strongly affected by the functional reorganization of neurocircuitry associated with kindling. The underlying mechanisms are discussed. The findings are relevant for a better understanding of kindling-associated network changes and might provide new targets for therapeutic manipulations in epilepsies.

Recent technological developments, such as single unit recordings coupled to optogenetic approaches, have provided unprecedented knowledge about the precise neuronal circuits contributing to the expression and recovery of conditioned fear behavior. These data have provided an understanding of the contributions of distinct brain regions such as the amygdala, prefrontal cortex, hippocampus, and periaqueductal gray matter to the control of conditioned fear behavior. Notably, the precise manipulation and identification of specific cell types by optogenetic techniques have provided novel avenues to establish causal links between changes in neuronal activity that develop in dedicated neuronal structures and the short and long-lasting expression of conditioned fear memories. In this review, we provide an update on the key neuronal circuits and cell types mediating conditioned fear expression and recovery and how these new discoveries might refine therapeutic approaches for psychiatric conditions such as anxiety disorders and posttraumatic stress disorder. [ABSTRACT FROM AUTHOR]

Lack of the anti-inflammatory and analgesic cytokine interleukin-4 (IL-4) is associated with mechanical hypersensitivity in mice, and low systemic levels of IL-4 are associated with pain in humans. We investigated whether the firing properties of murine nociceptive neurons in the spinal dorsal horn are affected by IL-4 deficiency. Single unit recordings from lumbar dorsal horn wide-dynamic-range (WDR) neurons were performed in IL-4 knock out (ko) mice and wild type (WT) littermates (3, 9, and 22 months old). We measured neuronal responses to innocuous (1 g) and noxious (26 g) von Frey mechanical stimulation at the plantar hind paw. Additionally, we induced secondary hyperalgesia by intraplantar injection of capsaicin and recorded discharges before and 5 and 10 min after injection. Baseline activity, activity upon innocuous stimulation, and postdischarges after noxious stimulation were not different between genotypes and ages. Responses to the noxious von Frey filament in 3 (34.5, 26.6–41.1 Hz) and 9 month old (49.7, 21.7–108.2 Hz) IL-4 ko mice were greater than in WT littermates (3 months, 18.1, 16.3–27.2 Hz, n.s.; 9 months, 33.6, 10.4–69.7 Hz; p < 0.05). In contrast, 22 month IL-4 ko mice had lower discharges (22.4, 16.8–28.9 Hz) than 3 and 9 month IL-4 ko mice (p < 0.01 each) and age-matched WT littermates (36.6, 10.4–59.4 Hz; n.s.). This pattern was also found 5 and 10 min after capsaicin injection. An enhanced excitability in the first segment of the nociceptive pathway may contribute to the increased behavioral responsiveness to painful stimuli of young IL-4 ko mice. [ABSTRACT FROM AUTHOR]

Identifying the properties of correlations in the firing of neocortical neurons is central to our understanding of cortical information processing. It has been generally assumed, by virtue of the columnar organization of the neocortex, that the firing of neurons residing in a certain vertical domain is highly correlated. On the other hand, firing correlations between neurons steeply decline with horizontal distance. Technical difficulties in sampling neurons with sufficient spatial information have precluded the critical evaluation of these notions. We used 128-channel "silicon probes" to examine the spike-count noise correlations during spontaneous activity between multiple neurons with identified laminar position and over large horizontal distances in the anesthetized rat barrel cortex. Eigen decomposition of correlation coefficient matrices revealed that the laminar position of a neuron is a significant determinant of these correlations, such that the fluctuations of layer 5B/6 neurons are in opposite direction to those of layers 5A and 4. Moreover, we found that within each experiment, the distribution of horizontal, intralaminar spike-count correlation coefficients, up to a distance of ~1.5 mm, is practically identical to the distribution of vertical correlations. Taken together, these data reveal that the neuron's laminar position crucially affects its role in cortical processing. Moreover, our analyses reveal that this laminar effect extends over several functional columns. We propose that within the cortex the influence of the horizontal elements exists in a dynamic balance with the influence of the vertical domain and this balance is modulated with brain states to shape the network's behavior. [ABSTRACT FROM AUTHOR]

In this account, we attempt to integrate two parallel, but thus far, separate lines of research on auditory novelty detection: (1) human studies of EEG recordings of the mismatch negativity ( MMN), and (2) animal studies of single-neuron recordings of stimulus-specific adaptation ( SSA). The studies demonstrating the existence of novelty neurons showing SSA at different levels along the auditory pathway's hierarchy, together with the recent results showing human auditory-evoked potential correlates of deviance detection at very short latencies, that is, at 20-40 ms from change onset, support the view that novelty detection is a key principle that governs the functional organization of the auditory system. Furthermore, the generation of the MMN recorded from the human scalp seems to involve a cascade of neuronal processing that occurs at different successive levels of the auditory system's hierarchy. [ABSTRACT FROM AUTHOR]

Abstract: The paraventricular nucleus (PVN) of hypothalamus is a major integrative center in homeostatic control. Morphological studies have revealed a high level of secretin and secretin receptor expression in the PVN. To investigate the direct electrophysiological effects of secretin in the PVN, in vivo extracellular recordings were performed in the present study. In 24 out of the 46 paraventricular neurons, micro-pressure ejection of secretin increased the firing rate from 3.07±0.43Hz to 4.86±0.70Hz. In another 8 out of the 46 paraventricular neurons, secretin decreased the firing rate from 2.61±0.46Hz to 1.41±0.25Hz. In the remaining 14 paraventricular neurons, secretin did not alter the firing rate significantly. The present findings provided direct electrophysiological evidence for the possible functions of secretin in the PVN. [Copyright &y& Elsevier]

Abstract: Morphological studies have shown that the globus pallidus receives dopaminergic innervation from the collaterals of nigrostriatal fibers. Dopamine D1-like receptors are expressed at both pre- and postsynaptic membrane. In the present study, we investigate the in vivo electrophysiological and behavioral effects of pallidal dopamine D1-like receptors in parkinsonian rats. On the lesioned side of 6-hydroxydopamine (6-OHDA) parkinsonian rats, micropressure ejection of dopamine D1-like receptor agonist, SKF38393, increased (88.2±18.6%) the firing rate in 10 out of the 32 pallidal neurons, but decreased (49.5±6.1%) the firing rate in 14 out of the 32 neurons. Furthermore, on the unlesioned side of parkinsonian rats, SKF38393 increased (43.0±6.3%) the firing rate in 9 out of the 30 pallidal neurons, but decreased (47.1±4.8%) the firing rate in 13 out of the 30 neurons. In behaving rats, unilateral microinjection of SKF38393 led to contralateral deflection in the presence of systemic haloperidol administration. The selective dopamine D1-like receptor antagonist, SCH23390, blocked both SKF38393-induced electrophysiological and behavioral effects. Combining electrophysiological and behavioral findings, we concluded that activation of dopamine D1-like receptors modulates the activity of globus pallidus neurons in rats. [Copyright &y& Elsevier]

Abstract: The globus pallidus in rodents, equivalent to the external globus pallidus in primates, plays an important role in movement regulation. Morphological studies have indicated that the globus pallidus receives dopamine innervation from the collaterals of nigrostriatal fibers. To investigate the direct electrophysiological effects of dopamine D1 receptors in the globus pallidus, in vivo extracellular recordings were performed in the present study. In 25 out of 58 globus pallidus neurons, micro-pressure ejection of 5mM SKF38393 increased the spontaneous firing rate from 9.8±1.9Hz to 14.3±2.5Hz. The average increase was 61.5±8.3% (P <0.001). In another 12 out of the 58 globus pallidus neurons, micro-pressure ejection of SKF38393 decreased the spontaneous firing rate from 4.7±1.2Hz to 2.1±0.6Hz. The average decrease was 52.1±6.7% (P <0.05). Micro-pressure ejection of SKF38393 did not alter the firing rate significantly in the left 21 globus pallidus neurons. The present findings may provide a rational for further investigations into the potential of pallidal dopamine D1 receptor in the treatment of Parkinson''s disease. [Copyright &y& Elsevier]

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Abstract: Selective serotonin reuptake inhibitors are the most widely prescribed antidepressant drugs. However, they exhibit a slow onset of action, putatively due to the initial decrease in serotonin cell firing mediated via somato-dendritic autoreceptors. Interestingly, blockade of 5-HT2C receptors significantly potentiates the effect of citalopram, a selective serotonin reuptake inhibitor, on serotonin efflux in the hippocampus and prefrontal cortex (Cremers, T.I.F.H., Giorgetti, M., Bosker, F.J., Hogg, S., Arnt, J., Mork, A., Honig, G., Bøgesø, K.P., Westerink, B.H.C., den Boer, J.A., Wikstrøm, H.V., Tecott, L.H., 2004. Inactivation of 5-HT2C receptors potentiates consequences of serotonin reuptake blockade. Neuropsychopharmacology 29, 1782–1789; Cremers, T.I.F.H., Rea, K., Bosker, F.J., Wikström, H.V., Hogg, S., Mørk, A., Westerink, B.H.C., 2007. Augmentation of SSRI effects on serotonin by 5-HT2C antagonists: mechanistic studies. Neuropsychopharmacology 32, 1550–1557.). Using in vivo electrophysiology, we show in the present study that the purported selective 5-HT2C receptor antagonist, SB242,084, dose-dependently counteracts citalopram-induced inhibition of serotonin cell firing. Even though the effect of SB242,084 is significant at a dose found in vivo to also partially occupy 5-HT2A receptors, indicating a possible contribution of a partial blockade of 5-HT2A receptors together with 5-HT2C receptors, we suggest that high occupancy at 5-HT2C receptors is essential for the blockade of the inhibitory effect of citalopram on 5-HT cell firing. Using microdialysis, we also show that the potentiation by SB242,084 on serotonin efflux requires an action of citalopram outside the terminal, most likely at the somato-dendritic level (i.e., on serotonin cell firing). Further experiments using local 5-HT2C receptor blockade indicate a role of 5-HT2C receptors located in the prefrontal cortex. Modulation of short or long feedback loops originating in the prefrontal cortex by 5-HT2C receptors could directly inhibit serotonin efflux, or alternatively, regulate serotonin cell firing in the dorsal raphe nucleus, thereby modulating serotonin efflux indirectly. [Copyright &y& Elsevier]

Abstract: Neurons in area PEc in the superior parietal cortex encode signals from different modalities, such as visual, extraretinal and somatosensory, probably combining them to encode spatial parameter of extrapersonal space to prepare body movements. This study reports the characterization of the functional properties of PEc non-visual neurons that showed saccade-related activity. We analyzed the pre- and post-saccadic firing activity in 189 neurons recorded in five hemispheres of three behaving monkeys. Spiking activity of PEc single neurons was recorded while the monkeys performed visually-guided saccades in a reaction time task. We found that 84% of neurons recorded from area PEc showed pre-saccadic activity with directional tuning. In 26% of neurons, we found inhibition of activity in the pre-saccadic period. The onset of this “pause” always started before the saccade and, in 51% of neurons, it was invariant among different gaze directions. The post-saccadic activity in these cells was either a phasic response with directional tuning (77%) and/or an eye position tuning (75%). The analysis of the preferred direction did not show hemispheric preference, however, for the majority of neurons, the angular difference in the preferred direction, in the pre- and post-saccadic period, was more than 60°. By confirming, therefore, that PEc neurons carry information about eye position, these novel findings open new horizons on PEc function that, to date, is not well documented. The pre-saccadic activity may reflect an involvement in saccade control, whereas post-saccadic activity may indicate a role in informing on the new eye position. These novel results about saccade and eye position processing may imply a role of area PEc in gaze direction mechanisms and, possibly, in remapping visual space after eye movements. [Copyright &y& Elsevier]

Abstract: Microelectrode arrays offer the auditory systems physiologists many opportunities through a number of electrode technologies. In particular, silicon substrate electrode arrays offer a large design space including choice of layout plan, range of surface areas for active sites, a choice of site materials and high spatial resolution. Further, most designs can double as recording and stimulation electrodes in the same preparation. Scala tympani auditory prosthesis research has been aided by mapping electrodes in the cortex and the inferior colliculus to assess the CNS responses to peripheral stimulation. More recently silicon stimulation electrodes placed in the auditory nerve, cochlear nucleus and the inferior colliculus have advanced the exploration of alternative stimulation sites for auditory prostheses. Multiplication of results from experimental effort by simultaneously stimulating several locations, or by acquiring several streams of data synchronized to the same stimulation event, is a commonly sought after advantage. Examples of inherently multichannel functions which are not possible with single electrode sites include (1) current steering resulting in more focused stimulation, (2) improved signal-to-noise ratio (SNR) for recording when noise and/or neural signals appear on more than one site and (3) current source density (CSD) measurements. Still more powerful are methods that exploit closely-spaced recording and stimulation sites to improve detailed interrogation of the surrounding neural domain. Here, we discuss thin-film recording/stimulation arrays on silicon substrates. These electrode arrays have been shown to be valuable because of their precision coupled with reproducibility in an ever expanding design space. The shape of the electrode substrate can be customized to accommodate use in cortical, deep and peripheral neural structures while flexible cables, fluid delivery and novel coatings have been added to broaden their application. The use of iridium oxide as the neural interface site material has increased the efficiency of charge transfer for stimulation and lowered impedance for recording electrodes. [Copyright &y& Elsevier]

Posterior parietal cortex is a region specialized for multimodal integration and coordinate transformations which converts sensory input to motor output. Eye position signals are crucial for such transformations, because they are needed to the inner reconstruction of a stable image of the outside world in spite of eye movements. Area 7m is a parietal area anatomically connected with oculomotor structures such as frontal eye field and superior colliculus. The aim of this study was to assess if neurons in area 7m possess activity related to eye movements, and if so, which sort of movements are processed. We recorded the extracellular activity of 7m neurons in two monkeys trained in both a smooth pursuit and a visually guided saccade task. The majority of neurons tested with the smooth pursuit task (16/17) showed directional selectivity influenced by the eye position. Moreover, these neurons were tuned to inward or outward pursuit with respect to the center of extra-personal visual space. About half of the cells (11/24) tested with the saccade task changed their activity during the pre-saccadic period. The majority of neurons presented post-saccadic activity: most of the cells showed a directionally-selective phasic response and a modulation by eye position during fixation (23/24). Overall, we observed that area 7m contains a population of neurons signaling smooth pursuit direction at certain eye position and saccade direction toward specific portions of the visual space. We hypothesize that area 7m might be involved in spatial map updating which can be used for spatial orientation. [ABSTRACT FROM AUTHOR]

Head direction cells, which are functionally coupled to ‘place’ cells of the hippocampus, a structure critically involved in spatial cognition, are likely neural substrates for the sense of direction. Here we studied the mechanism by which head direction cells are principally anchored to background visual cues [M.B. Zugaro et al. (2001) J. Neurosci., 21, RC154,1–5]. Anterodorsal thalamic head direction cells were recorded while the rat foraged on a small elevated platform in a 3-m diameter cylindrical enclosure. A large card was placed in the background, near the curtain, and a smaller card was placed in the foreground, near the platform. The cards were identically marked, proportionally dimensioned, subtended the same visual angles from the central vantage point and separated by 90°. The rat was then disoriented in darkness, the cards were rotated by 90° in opposite directions about the center and the rat was returned. Preferred directions followed either the background card, foreground card or midpoint between the two cards. In continuous lighting, preferred directions shifted to follow the background cue in most cases (30 of the 53 experiments, Batschelet V-test, P < 0.01). Stroboscopic illumination, which perturbs dynamic visual signals (e.g. motion parallax), blocked this selectivity. Head direction cells remained equally anchored to the background card, foreground card or configuration of the two cards (Watson test, P > 0.1). This shows that dynamic visual signals are critical in distinguishing typically more stable background cues which govern spatial neuronal responses and orientation behaviors. [ABSTRACT FROM AUTHOR]

Summary. Extracellular electrophysiological recordings of neurons of the parafascicular nucleus of the thalamus were done in normal rats and in rats bearing lesions of either the cerebellar nuclei or the entopeduncular nucleus to investigate the functional control of the pedunculopontine nucleus on the parafascicular nucleus. A total of 97 neurons were recorded in the parafascicular nucleus in intact rats, 83 in rats bearing a chronic electrolytic lesion of the ipsilateral deep cerebellar nuclei, and 69 in rats bearing an ibotenate lesion of the ipsilateral entopeduncular nucleus. Lesions of the cerebellar nuclei or the entopeduncular nucleus were made to evaluate the participation of cerebellothalamic fibers or of polysynaptic basal ganglia circuits in the responses recorded in parafascicular neurons following electrical microstimulation of the ipsilateral pedunculopontine nucleus. Two types of excitation and one type of inhibition were the main responses observed in neurons of the parafascicular nucleus following stimulation of the pedunculopontine nucleus. The first type of excitation, observed in 49.5% of neurons recorded in normal rats, had an onset of 1.8 ± 0.6 ms, lasted 9.2 ± 0.8 ms and was able to follow high frequency stimulation over 300 Hz. The second type of excitation, observed in a smaller percentage of neurons recorded (3.1%), was a long-latency (8.3 ± 0.7 ms) activation lasting 19.0 ± 4.5 ms. It did not follow stimulation frequencies higher than 50–100 Hz. The inhibitory response was observed in 17.5% of the neurons recorded. The latency of this inhibition was 4.5 ± 1.8 ms and the duration 41.9 ± 6.8 ms. In rats bearing a lesion of the deep cerebellar nuclei or of the entopeduncular nucleus, the short-latency activation was still present in 24.1% and 31.9% of neurons recorded, respectively. However, the occurrence of the long-latency excitation rats bearing lesions of either the cerebellum or the entopeduncular nucleus increased to 12.1% and to 17.4%, respectively, while the occurrence of the inhibition rose to 22.9% and to 28.9%. These results show that an excitatory influence on the parafascicular nucleus is exerted by the pedunculopontine nucleus irrespectively of the presence of cerebellofugal fibers. This influence appears to be also independent from the integrity of basal ganglia circuits having a relay at the level of the entopeduncular nucleus. However, the variety of responses recorded suggests that the influences of the pedunculopontine nucleus on the parafascicular nucleus are by far more complex than those exerted on its basal ganglia targets such as the substantia nigra. The results are discussed according to a model of functioning of pedunculopontine fibers directed to thalamic and basal ganglia nuclei. [ABSTRACT FROM AUTHOR]

Abstract In the primary visual cortex of normally reared adult cat, neurons activated through the corpus callosum are almost entirely located at the 17/18 border. They display small receptive fields distributed along the central vertical meridian of the visual field and are orientation selective. Here we demonstrate that a few weeks of monocular deprivation or unilateral convergent strabismus produced in adulthood does not modify the cortical distribution of these neurons, but leads to an increase of their receptive field size mainly toward the ipsilateral hemifield and to a loss of their orientation selectivity. We conclude that manipulation of binocular vision in the adult modifies neither the location of the primary callosal cortical map nor its retinotopy. In contrast, it induces functional plastic changes in this map which lead to a significant widening of the area of visual space signalled through the corpus callosum. These plastic changes are interpreted as the result of the strengthening of normally hidden subthreshold synaptic inputs. [ABSTRACT FROM AUTHOR]

We investigated the effects of the novel 5-HT1A receptor agonist BAY x 3702 on the serotonergic function in rat brain using single unit recordings in the dorsal raphe nucleus (DR) of anesthetized rats and in vivo microdialysis in freely moving rats. The administration of BAY x 3702 (0.25–4 µg/kg i.v.) suppressed the firing activity of 5-HT neurones. This effect was antagonized by a low dose of the selective 5-HT1A receptor antagonist WAY 100635 (5 µg/kg i.v.). In microdialysis experiments, BAY x 3702 (10–100 µg/kg s.c.) reduced dose-dependently the 5-HT output in the dorsal and median raphe (MnR) nucleus, dorsal hippocampus (DHPC) and medial prefrontal cortex (mPFC) in a regionally selective manner. Maximal effects were observed in the MnR and mPFC, with reductions to ~15% of baseline at a dose of 0.1 mg/kg s.c. The decrease in 5-HT output produced in the DR and DHPC was more moderate, to 45% of baseline at 0.1 mg/kg s.c. BAY x 3702. WAY 100635 (0.3 mg/kg s.c.) completely antagonized the effect of BAY x 3702 (30 µg/kg s.c.). The application of BAY x 3702 in the DR (1–100 µM) reduced the local 5-HT output to 25% of baseline. In rats implanted with two dialysis probes (in DR and mPFC) the application of BAY x 3702 (30 µM) in the DR reduced the 5-HT output in the DR and that in mPFC. These effects were significantly antagonized by the co-perfusion of WAY 100635 (100 µM) in the DR. Overall, these results indicate that the systemic administration of BAY x 3702 reduces the 5-HT release with high potency through the activation of midbrain 5-HT1A receptors. [ABSTRACT FROM AUTHOR]

We studied the actions of intoxicating doses of ethanol on excitatory inputs from the basolateral nucleus of the amygdala, a major afferent system projecting to the nucleus accumbens (NAcc). In view of the hypothesized role of opioid receptors on the effects of ethanol on NAcc physiology, we also explored whether naloxone modulates ethanol-induced suppression of NAcc excitability in halothane anesthetized and freely moving unanesthetized rats. Intraperitoneal administration of ethanol (1.2-1.4 g/kg) markedly suppressed a subgroup of amygdala-activated NAcc neurons. The ethanol-induced reduction in amygdala-activated NAcc neurons was not reversed by naloxone (5.0 mg/kg, intraperitoneally). Moreover, naloxone had no effect on the supressive effects of ethanol on NAcc spontaneous activity in either halothane-anesthetized or unanesthetized freely moving preparations. These findings suggest that opiate mechanisms either are not participating or are not solely responsible for the inhibitory effects of acute intoxicating doses of ethanol on NAcc physiology. [ABSTRACT FROM AUTHOR]

To test for access of spatial cues to the hippocampus of unrestrained animals, single unit recordings of CA1 complex spike cells were made in thirsty rats as they made alternating visits between the center and corners of an enclosed 60×60 cm square arena. At intervals, all lights were turned off in the arena and it was rotated. Although no neuronal discharge activity was found that encoded the rotation angle, 11 of 97 neurons were selectively activated after lights were turned off or on. This activity began at delays of up to several seconds and persisted for tens of seconds. These discharges had no location selectivity or behavioral correlates and continued even as the rat performed several behaviors in different parts of the arena. This confirms similar results in restrained rabbits while showing for the first time that this neuronal activity can be independent of place and behavior. In addition this shows that sensory stimuli can trigger hippocampal discharges even when the rat is not required to make any behavioral responses to them. [ABSTRACT FROM AUTHOR]

We have recorded neuronal responses in the lateral temporal lobe of man to overt speech during open brain surgery for epilepsy. Tests included overt naming of objects and reading words or short sentences shown on a projector screen, repetition of tape recorded words or sentences presented over a loudspeaker, and free conversation. Neuronal activity in the dominant and non-dominant temporal lobe were about equally affected by overt speech. As during listening to language (see Creutzfeldt et al. 1989), responses differed between recordings from sites in the superior and the middle or inferior temporal gyrus. In the superior temporal gyrus all neurons responded clearly and each in a characteristic manner. Activation could be related to phonemic aspects, to segmentation or to the length of spoken words or sentences. However, neurons were mostly differently affected by listening to words and language as compared to overt speaking. In neuronal populations recorded simultaneously with one or two microelectrodes, some neurons responded predominantly to one or the other type of speech. Excitatory responses during overt speaking were always auditory. In the middle temporal gyrus more neurons (about 2/3) responded to overt speaking than to listening alone. Activations elicited during overt speech were seen in about 1/3 of our sample, but they were more sluggish than those recorded in the superior gyrus. A prominent feature was suppression of on-going activity, which we found in about 1/3 of middle and in some superior temporal gyrus neurons. This suppression could preced vocalization by up to a few hundred ms, and could outlast it by up to 1 s. Evoked ECoG-potentials to words heard or spoken were different, and those to overt speech were more widespread. [ABSTRACT FROM AUTHOR]

Receptive field (RF) characteristics of cells in primary visual cortex of the mouse (C57B16 strain) were studied by single unit recording. We have studied the functional organization of area 17 along both the radial and tangential dimensions of the cortex. Eighty seven percent of the visual neurons could be classified according to their responses to oriented stimuli and to moving stimuli. Cells which preferred a flashed or moving bar of a particular orientation and responded less well to bars of other orientations or to spots, were classified as orientation selective (simple RF 23%, complex RF 18%). The majority of them were, moreover, unidirectional (24%). All orientations were roughly equally represented. Cells with oriented RFs were recorded mostly in the upper part of cortical layers II-III, where they appeared to be clustered according to their preferred orientation. Neurons that responded equally well to spots and bars of all orientations (46%) were classified as 'non-oriented'; among these neurons there were several subcategories. Cells which responded equally well to spots and bars but preferred stimuli moving along one or both directions of a particular axis were classified as non oriented asymmetric cells (unidirectional 14%, bidirectional 4%). They were recorded mainly in supra- and infra-granular layers. Cells unaffected by stimulus shape and orientation which responded equally well to all directions of movement were classified as symmetric units. They had receptive field classified as ON (11%), OFF (1%), ON/ OFF (11%), or were unresponsive to stationary stimuli (5%). These cells were mostly found in layer IV, in which they constituted the majority of recorded cells. There was no apparent correlation between the functional type and size of RFs. However, the greatest proportion of small RFs was found in layer IV. In the binocular segment of the mouse striate cortex, the influence of the contralateral eye predominated. Ninety five percent of cells in this segment were driven through the contralateral eye. However, 70% of cells were binocularly activated, showing that considerable binocular integration occured in this cortical segment. Ocular dominance varied less along the radial than along the tangential dimension of the cortex. [ABSTRACT FROM AUTHOR]

Objective . The goal of this study is to decode the electrical activity of single neurons in the human subthalamic nucleus (STN) to infer the speech features that a person articulated, heard or imagined. We also aim to evaluate the amount of subthalamic neurons required for high accuracy decoding suitable for real-life speech brain-machine interfaces (BMI). Approach . We intraoperatively recorded single-neuron activity in the STN of 21 neurosurgical patients with Parkinson's disease undergoing implantation of deep brain stimulator while patients produced, perceived or imagined the five monophthongal vowel sounds. Our decoder is based on machine learning algorithms that dynamically learn specific features of the speech-related firing patterns. Main results . In an extensive comparison of algorithms, our sparse decoder ('SpaDe'), based on sparse decomposition of the high dimensional neuronal feature space, outperformed the other algorithms in all three conditions: production, perception and imagery. For speech production, our algorithm, Spade, predicted all vowels correctly (accuracy: 100%; chance level: 20%). For perception accuracy was 96%, and for imagery: 88%. The accuracy of Spade showed a linear behavior in the amount of neurons for the perception data, and even faster for production or imagery. Significance . Our study demonstrates that the information encoded by single neurons in the STN about the production, perception and imagery of speech is suitable for high-accuracy decoding. It is therefore an important step towards BMIs for restoration of speech faculties that bears an enormous potential to alleviate the suffering of completely paralyzed ('locked-in') patients and allow them to communicate again with their environment. Moreover, our research indicates how many subthalamic neurons may be necessary to achieve each level of decoding accuracy, which is of supreme importance for a neurosurgeon planning the implantation of a speech BMI., (© 2021 IOP Publishing Ltd.)

Background: Chronic migraine (CM) is a highly debilitating disease, and many patients remain refractory to medicinal therapy. Given the convergent nature of neuronal networks in the ventral posteromedial nucleus (VPM) and the evidence of sensitization of pain circuitry in this disease, we hypothesize CM rats will have increased VPM neuronal firing, which can be attenuated using occipital nerve stimulation (ONS)., Objective: To determine whether VPM firing frequency differs between CM and sham rats, and whether ONS significantly alters firing rates during the application of mechanical stimuli., Methods: Fourteen male Sprague-Dawley rats were infused with inflammatory media once daily through an epidural cannula for 2 wk to induce a CM state. Sham animals (n = 6) underwent cannula surgery but received no inflammatory media. ONS electrodes were implanted bilaterally and single-unit recordings were performed in the VPM of anesthetized rats during mechanical stimulation of the face and forepaw in the presence and absence of ONS., Results: CM rats had significantly higher neuronal firing rates (P < .001) and bursting activity (P < .01) in response to mechanical stimuli when compared to shams. ONS significantly reduced neuronal firing in the VPM of CM rats during the application of 0.8 g (P = .04), 4.0 g (P = .04), and 15.0 g (P = .02) Von Frey filaments. ONS reduced bursting activity in CM rats during the 4.0 and 15 g filaments (P < .05). No significant changes in bursting activity or firing frequency were noted in sham animals during ONS., Conclusion: We demonstrate that neuronal spike frequencies and bursting activity in the VPM are increased in an animal model of CM compared to shams. Our results suggest that the mechanism of ONS may involve attenuation of neurons in the VPM of CM rats during the application of mechanical stimuli., (Copyright © 2017 by the Congress of Neurological Surgeons)