Extracellular Neuronal Activity Research Articles

A method for chronic and semi-chronic microelectrode array implantation in deep brain structures using image guided neuronavigation

BackgroundAccurate targeting of brain structures for in-vivo electrophysiological recordings is essential for basic as well as clinical neuroscience research. Although methodologies for precise targeting and recording from the cortical surface are abundant, such protocols are scarce for deep brain structures. New methodWe have incorporated stable fiducial markers within a custom cranial cap for improved image-guided neuronavigation targeting of subcortical structures in macaque monkeys. Anchor bolt chambers allowed for a minimally invasive entrance into the brain for chronic recordings. A 3D-printed microdrive allowed for semi-chronic applications. ResultsWe achieved an average Euclidean targeting error of 1.6 mm and a radial error of 1.2 mm over three implantations in two animals. Chronic and semi-chronic implantations allowed for recording of extracellular neuronal activity, with single-neuron activity examples shown from one macaque monkey. Comparison with existing method(s)Traditional stereotactic methods ignore individual anatomical variability. Our targeting approach allows for a flexible, subject-specific surgical plan with targeting errors lower than what is reported in humans, and equal to or lower than animal models using similar methods. Utilizing an anchor bolt as a chamber reduced the craniotomy size needed for electrode implantation, compared to conventional large access chambers which are prone to infection. Installation of an in-house, 3D-printed, screw-to-mount mechanical microdrive is in contrast to existing semi-chronic methods requiring fabrication, assembly, and installation of complex parts. ConclusionsLeveraging commercially available tools for implantation, our protocol decreases the risk of infection from open craniotomies, and improves the accuracy of chronic electrode implantations targeting deep brain structures in large animal models.

Human acute microelectrode array recordings with broad cortical access, single-unit resolution, and parallel behavioral monitoring

There are vast gaps in our understanding of the organization and operation of the human nervous system at the level of individual neurons and their networks. Here, we report reliable and robust acute multichannel recordings using planar microelectrode arrays (MEAs) implanted intracortically in awake brain surgery with open craniotomies that grant access to large parts of the cortical hemisphere. We obtained high-quality extracellular neuronal activity at the microcircuit, local field potential level and at the cellular, single-unit level. Recording from the parietal association cortex, a region rarely explored in human single-unit studies, we demonstrate applications on these complementary spatial scales and describe traveling waves of oscillatory activity as well as single-neuron and neuronal population responses during numerical cognition, including operations with uniquely human number symbols. Intraoperative MEA recordings are practicable and can be scaled up to explore cellular and microcircuit mechanisms of a wide range of human brain functions.

Predicting in vitro single-neuron firing rates upon pharmacological perturbation using Graph Neural Networks.

Modern Graph Neural Networks (GNNs) provide opportunities to study the determinants underlying the complex activity patterns of biological neuronal networks. In this study, we applied GNNs to a large-scale electrophysiological dataset of rodent primary neuronal networks obtained by means of high-density microelectrode arrays (HD-MEAs). HD-MEAs allow for long-term recording of extracellular spiking activity of individual neurons and networks and enable the extraction of physiologically relevant features at the single-neuron and population level. We employed established GNNs to generate a combined representation of single-neuron and connectivity features obtained from HD-MEA data, with the ultimate goal of predicting changes in single-neuron firing rate induced by a pharmacological perturbation. The aim of the main prediction task was to assess whether single-neuron and functional connectivity features, inferred under baseline conditions, were informative for predicting changes in neuronal activity in response to a perturbation with Bicuculline, a GABA A receptor antagonist. Our results suggest that the joint representation of node features and functional connectivity, extracted from a baseline recording, was informative for predicting firing rate changes of individual neurons after the perturbation. Specifically, our implementation of a GNN model with inductive learning capability (GraphSAGE) outperformed other prediction models that relied only on single-neuron features. We tested the generalizability of the results on two additional datasets of HD-MEA recordings-a second dataset with cultures perturbed with Bicuculline and a dataset perturbed with the GABA A receptor antagonist Gabazine. GraphSAGE models showed improved prediction accuracy over other prediction models. Our results demonstrate the added value of taking into account the functional connectivity between neurons and the potential of GNNs to study complex interactions between neurons.

Revisiting the involvement of tau in complex neural network remodeling: analysis of the extracellular neuronal activity in organotypic brain slice co-cultures

Objective. Tau ablation has a protective effect in epilepsy due to inhibition of the hyperexcitability/hypersynchrony. Protection may also occur in transgenic models of Alzheimer’s disease by reducing the epileptic activity and normalizing the excitation/inhibition imbalance. However, it is difficult to determine the exact functions of tau, because tau knockout (tauKO ) brain networks exhibit elusive phenotypes. In this study, we aimed to further explore the physiological role of tau using brain network remodeling. Approach. The effect of tau ablation was investigated in hippocampal-entorhinal slice co-cultures during network remodeling. We recorded the spontaneous extracellular neuronal activity over 2 weeks in single-slice cultures and co-cultures from control and tauKO mice. We compared the burst activity and applied concepts and analytical tools intended for the analysis of the network synchrony and connectivity. Main results. Comparison of the control and tauKO co-cultures revealed that tau ablation had an anti-synchrony effect on the hippocampal-entorhinal two-slice networks at late stages of culture, in line with the literature. Differences were also found between the single-slice and co-culture conditions, which indicated that tau ablation had differential effects at the sub-network scale. For instance, tau ablation was found to have an anti-synchrony effect on the co-cultured hippocampal slices throughout the culture, possibly due to a reduction in the excitation/inhibition ratio. Conversely, tau ablation led to increased synchrony in the entorhinal slices at early stages of the co-culture, possibly due to homogenization of the connectivity distribution. Significance. The new methodology presented here proved useful for investigating the role of tau in the remodeling of complex brain-derived neural networks. The results confirm previous findings and hypotheses concerning the effects of tau ablation on neural networks. Moreover, the results suggest, for the first time, that tau has multifaceted roles that vary in different brain sub-networks.

Galvanic vestibular stimulation down-regulated NMDA receptors in vestibular nucleus of PD model

Parkinsonian symptoms relief by electrical stimulation is constructed by modulating neural network activity, and Galvanic vestibular stimulation (GVS) is known to affect the neural activity for motor control by activating the vestibular afferents. However, its underlying mechanism is still elusive. Due to the tight link from the peripheral vestibular organ to vestibular nucleus (VN), the effect by GVS was investigated to understand the neural mechanism. Using Sprague Dawley (SD) rats, behavioral response, extracellular neural recording, and immunohistochemistry in VN were conducted before and after the construction of Parkinson’s disease (PD) model. Animals’ locomotion was tested using rota-rod, and single extracellular neuronal activity was recorded in VN. The immunohistochemistry detected AMPA and NMDA receptors in VN to assess the effects by different amounts of electrical charge (0.018, 0.09, and 0.18 coulombs) as well as normal and PD with no GVS. All PD models showed the motor impairment, and the loss of TH+ neurons in medial forebrain bundle (mfb) and striatum was observed. Sixty-five neuronal extracellular activities (32 canal & 33 otolith) were recorded, but no significant difference in the resting firing rates and the kinetic responding gain were found in the PD models. On the other hand, the numbers of AMPA and NMDA receptors increased after the construction of PD model, and the effect by GVS was significantly evident in the change of NMDA receptors (p < 0.018). In conclusion, the increased glutamate receptors in PD models were down-regulated by GVS, and the plastic modulation mainly occurred through NMDA receptor in VN.

Heptafluoroisobutyronitrile (C4F7N), a gas used for insulating and arc quenching in electrical switchgear, is neurotoxic in the mouse brain

Fluoronitrile gas (C4F7N, CAS number 42532-60-5) is one of the most promising candidates as insulating and/or breaking medium in high and medium voltage electrical equipment. Besides its promising properties, C4F7N gas is however not devoid of acute toxicity when used pure or in gas mixtures. The toxicity was not extensively analyzed and reported. The aim of the present study was to analyze in mice the consequences of a single exposure to C4F7N gas, at different concentrations and different timepoints after exposure. Male and female Swiss mice were exposed to breathable air or C4F7N gas, at 800 ppmv or 1500 ppmv, for 4 h on day 0. Behavioral tests (spontaneous alternation in the Y-maze and object recognition) were performed on days 1, 7 and 14 to assess memory alterations. The animals were then sacrificed and their brains dissected for biochemical analyses or fixed with paraformaldehyde for histology and immunohistochemistry. Results showed behavioral impairments and memory deficits, with impairments of alternation at days 1 and 7 and object recognition at day 14. Histological alterations of pyramidal neuronal layer in the hippocampus, neuroinflammatory astroglial reaction, and microglial alterations were observed, more marked in female than male mice. Moreover, the biochemical analyses done in the brain of 1500 ppmv exposed female mice showed a reductive stress with decreased lipid peroxidation and release of cytochrome c, leading to apoptosis with increases in caspase-9 cleavage and γ-H2AX/H2AX ratio. Finally, electrophysiological analyses using a multi-electrode array allowed the measure of the extracellular activity of pyramidal neurons in the CA2 area and revealed that exposure to the gas not only prevented the induction of long-term potentiation but even provoked an epileptoid-like activity in some neurons suggesting major alterations of synaptic plasticity. This study therefore showed that an acute exposure of mice to C4F7N gas provoked, particularly in female animals, memory alterations and brain toxicity characterized by a reductive stress, microglial toxicity, loss of synaptic plasticity and apoptosis. Its use in industrial installations must be done with extreme caution.

TinyLFP: A Tiny Local-Field-Potential Sensor

Efficient acquisition and analysis of neural signals play a significant role in enhancing our understanding of the brain function and its abnormalities. Neural interfaces involve electrodes inserted into the brain tissues, and also hardware circuits and software to record neural activities and analyze them. Local field potentials (LFPs) are the low frequency neural signals recorded invasively capturing the dynamic extracellular neuronal activities. The information on different bands of neural oscillations (alpha, beta, theta, and gamma) in LFP signals has been used to determine brain abnormalities. LFP signals contain components with amplitudes in the range of 10- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$100 ~\mu \text{V}$ </tex-math></inline-formula> , which are small and can be easily distorted by external noise sources. With the advancements in closed-loop brain stimulation paradigms, there is a need for miniaturized sensors to capture and monitor LFP signals. The sensed LFP signals can then be used to close the feedback loop in a control system to adjust stimulation parameters in a closed-loop brain stimulation device. A LFP sensor requires a low power circuit to ensure prolonged operation. In addition, an area-efficient and low-noise front end stage needs to be formed. Considering these requirements, a single-channel, power-efficient, low-noise, compact neural sensor for acquisition of LFP signals is presented. The miniaturized LFP sensor, named TinyLFP, has a low-noise first stage instrumentation amplifier for providing a pre-amplification of 100 V/V, a band pass filter with a pass band of 4–200 Hz, and a post amplifier stage with an amplification factor of 200 V/V. Overall, the device provides a gain of around 85 dB for the signals in the range of 4 to 200 Hz to be used as the first stage of a closed loop optogenetic brain stimulation device.

Implantation of Neuropixels probes for chronic recording of neuronal activity in freely behaving mice and rats.

How dynamic activity in neural circuits gives rise to behavior is a major area of interest in neuroscience. A key experimental approach for addressing this question involves measuring extracellular neuronal activity in awake, behaving animals. Recently developed Neuropixels probes have provided a step change in recording neural activity in large tissue volumes with high spatiotemporal resolution. This protocol describes the chronic implantation of Neuropixels probes in mice and rats using compact and reusable 3D-printed fixtures. The fixtures facilitate stable chronic in vivo recordings in freely behaving rats and mice. They consist of two parts: a covered main body and a skull connector. Single-, dual- and movable-probe fixture variants are available. After completing an experiment, probes are safely recovered for reimplantation by a dedicated retrieval mechanism. Fixture assembly and surgical implantation typically take 4-5 h, and probe retrieval takes ~30 min, followed by 12 h of incubation in probe cleaning agent. The duration of data acquisition depends on the type of behavioral experiment. Since our protocol enables stable, chronic recordings over weeks, it enables longitudinal large-scale single-unit data to be routinely obtained in a cost-efficient manner, which will facilitate many studies in systems neuroscience.

ApoE4 attenuates cortical neuronal activity in young behaving apoE4 rats

The E4 allele of apolipoprotein E (apoE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). However, apoE4 may cause innate brain abnormalities before the appearance of AD-related neuropathology. Understanding these primary dysfunctions is vital for the early detection of AD and the development of therapeutic strategies. Recently we reported impaired extra-hippocampal memory in young apoE4 mice, a deficit that was correlated with attenuated structural pre-synaptic plasticity in cortical and subcortical regions. Here we tested the hypothesis that these early structural deficits impact learning via changes in basal and stimuli evoked neuronal activity. We recorded extracellular neuronal activity from the gustatory cortex (GC) of three-month-old humanized apoE4 (hApoE4) and wildtype rats expressing rat apoE (rAE), before and after conditioned taste aversion (CTA) training. Despite normal sucrose drinking behavior before CTA, young hApoE4 rats showed impaired CTA learning, consistent with our previous results in target-replacement apoE4 mice. This behavioral deficit was correlated with decreased basal and taste-evoked firing rates in both putative excitatory and inhibitory GC neurons. Further taste coding analyses at the single neuron and ensemble levels revealed that GC neurons of the hApoE4 group correctly classified tastes, but were unable to undergo plasticity to support learning. These results suggest that apoE4 impacts brain excitability and plasticity early in life that may act as an initiator for later AD pathologies.

Overexpression of Isl1 under the Pax2 Promoter, Leads to Impaired Sound Processing and Increased Inhibition in the Inferior Colliculus

The LIM homeodomain transcription factor ISL1 is essential for the different aspects of neuronal development and maintenance. In order to study the role of ISL1 in the auditory system, we generated a transgenic mouse (Tg) expressing Isl1 under the Pax2 promoter control. We previously reported a progressive age-related decline in hearing and abnormalities in the inner ear, medial olivocochlear system, and auditory midbrain of these Tg mice. In this study, we investigated how Isl1 overexpression affects sound processing by the neurons of the inferior colliculus (IC). We recorded extracellular neuronal activity and analyzed the responses of IC neurons to broadband noise, clicks, pure tones, two-tone stimulation and frequency-modulated sounds. We found that Tg animals showed a higher inhibition as displayed by two-tone stimulation; they exhibited a wider dynamic range, lower spontaneous firing rate, longer first spike latency and, in the processing of frequency modulated sounds, showed a prevalence of high-frequency inhibition. Functional changes were accompanied by a decreased number of calretinin and parvalbumin positive neurons, and an increased expression of vesicular GABA/glycine transporter and calbindin in the IC of Tg mice, compared to wild type animals. The results further characterize abnormal sound processing in the IC of Tg mice and demonstrate that major changes occur on the side of inhibition.

Spatio-temporal characterization of causal electrophysiological activity stimulated by single pulse focused ultrasound: an ex vivo study on hippocampal brain slices

Objective. The brain operates via generation, transmission and integration of neuronal signals and most neurological disorders are related to perturbation of these processes. Neurostimulation by focused ultrasound (FUS) is a promising technology with potential to rival other clinically used techniques for the investigation of brain function and treatment of numerous neurological diseases. The purpose of this study was to characterize spatial and temporal aspects of causal electrophysiological signals directly stimulated by short, single pulses of FUS on ex vivo mouse hippocampal brain slices. Approach. Microelectrode arrays (MEAs) are used to study the spatio-temporal dynamics of extracellular neuronal activities both at the single neuron and neural networks scales. Hence, MEAs provide an excellent platform for characterization of electrical activity generated, modulated and transmitted in response to FUS exposure. In this study, a novel mixed FUS/MEA platform was designed for the spatio-temporal description of the causal responses generated by single 1.78 MHz FUS pulses in ex vivo mouse hippocampal brain slices. Main results. Our results show that FUS pulses can generate local field potentials (LFPs), sustained by synchronized neuronal post-synaptic potentials, and reproducing network activities. LFPs induced by FUS stimulation were found to be repeatable to consecutive FUS pulses though exhibiting a wide range of amplitudes (50–600 μV), durations (20–200 ms), and response delays (10–60 ms). Moreover, LFPs were spread across the hippocampal slice following single FUS pulses thus demonstrating that FUS may be capable of stimulating different neural structures within the hippocampus. Significance. Current knowledge on neurostimulation by ultrasound describes neuronal activity generated by trains of repetitive ultrasound pulses. This novel study details the causal neural responses produced by single-pulse FUS neurostimulation while illustrating the distribution and propagation properties of this neural activity along major neural pathways of the hippocampus.

Wireless logging of extracellular neuronal activity in the telencephalon of free-swimming salmonids

BackgroundSalmonids return to the river where they were born in a phenomenon known as mother-river migration. The underpinning of migration has been extensively examined, particularly regarding the behavioral correlations of external environmental cues such as the scent of the mother-river and geomagnetic compass. However, neuronal underpinning remains elusive, as there have been no biologging techniques suited to monitor neuronal activity in the brain of large free-swimming fish. In this study, we developed a wireless biologging system to record extracellular neuronal activity in the brains of free-swimming salmonids.ResultsUsing this system, we recorded multiple neuronal activities from the telencephalon of trout swimming in a rectangular water tank. As proof of principle, we examined the activity statistics for extracellular spike waveforms and timing. We found cells firing maximally in response to a specific head direction, similar to the head direction cells found in the rodent brain. The results of our study suggest that the recorded signals originate from neurons.ConclusionsWe anticipate that our biologging system will facilitate a more detailed investigation into the neural underpinning of fish movement using internally generated information, including responses to external cues.

Сравнительный анализ активности нейронов префронтальной коры мозга крыс в состоянии продуктивной и непродуктивной работы

The goal of the work was to study the prefrontal cortex neural activity in the different neuropsychological conditions of the animal. Extracellular neuron activity of the prefrontal cortex rat brain was recorded in rats performing the behavioral task of choice in the two-ring maze. On each experimental day, in the sequence of trials, periods of efficient and ineffective work were distinguished, differing in the prevalence of correct or incorrect choice. A comparative analysis of the neuron activity in six different variants of behavior revealed a significant difference in one pattern of neural activity accompanying reinforced trials to the one side in the ineffective condition. It is assumed that this is due to the activation of a previously formed pattern of behavior such leads to a probabilistic choice strategy. A dynamic mechanism of changing some decision-making strategies depending on the neuropsychological conditions of the animal is assumed, manifested in the inhibition of old models during training in a efficient state and a weakening of such a control mechanism in an ineffective state.

A novel deep LSTM network for artifacts detection in microelectrode recordings

Microelectrode recording (MER) signals are world-widely used for validating the planned trajectories in the procedure of deep brain stimulation (DBS) surgery to obtain accurate position of electrodes inside the brain structure. Besides, MER signals are important source for studying extracellular neuronal activity and DBS biomarkers, such as, spike clustering and sorting. However, MER signals are prone to several artifacts derived from electrical equipment in the operating room, electrode movement and patient activities, etc., which reduce the signal-to-noise ratio of the MER signals. Therefore, in this paper, we propose a novel deep learning architecture based on long short-term memory (LSTM) network for automatic artifact detection in MER signals. Frequency and time-domain features were extracted from the raw MER signals and fed to the deep LSTM network. A manually annotated MER database obtained from 17 Parkinson's disease (PD) patients were used to validate the proposed architecture. The proposed architecture achieved promising results of 97.49% accuracy, 98.21% sensitivity and 96.87% specificity on an unseen test set. To our best knowledge, this is the first study to use LSTM network for artifacts detection in MER signals. The MER data will be available at http://homepage.hit.edu.cn/wpgao.

Effects of sevoflurane and desflurane on the nociceptive responses of substantia gelatinosa neurons in the rat spinal cord dorsal horn: An in vivo patch-clamp analysis.

BackgroundVolatile anesthetics suppress noxiously evoked activity in the spinal dorsal horn, which could contribute in part to analgesia, immobility. Modulation of excitatory and inhibitory synaptic transmission in substantia gelatinosa neurons could lead to the suppression of dorsal horn activity; however, this phenomenon has not yet been investigated fully.MethodsIn urethane-anesthetized rats, extracellular activity of dorsal horn neurons (action potentials) and excitatory/inhibitory postsynaptic currents in substantia gelatinosa neurons were recorded using extracellular and in vivo patch-clamp techniques, respectively, to assess the spontaneous and the noxious-evoked activity. Sevoflurane or desflurane at concentrations ranging from 0.1 to 2 minimum alveolar concentration was administered by inhalation. Hot- and cold-plate tests were performed to assess nociceptive responses during the inhalation of volatile anesthetics at lower anesthetic doses (0.1–0.5 minimum alveolar concentration).ResultsAt anesthetic doses (1 and 2 minimum alveolar concentration), both sevoflurane and desflurane decreased the frequency of action potentials in the dorsal horn and the activities of excitatory postsynaptic currents in substantia gelatinosa neurons during pinch stimulation and decreased the activities of spontaneous and miniature excitatory postsynaptic currents. Inhibition of the frequencies was more prominent than that of amplitudes in spontaneous and miniature excitatory postsynaptic currents at these anesthetic doses. However, at subanesthetic doses (0.1 and 0.2 minimum alveolar concentration), desflurane facilitated action potentials and excitatory postsynaptic currents. Inhibitory postsynaptic currents were inhibited by both anesthetics at anesthetic doses (1 and 2 minimum alveolar concentration). Hot- or cold-plate tests showed hyperalgesic effects of desflurane at subanesthetic doses (0.1 and 0.2 minimum alveolar concentration) and a dose-dependent analgesic effect of sevoflurane.ConclusionsSevoflurane and desflurane at anesthetic doses suppressed dorsal horn activity mainly via inhibition of excitatory postsynaptic currents in substantia gelatinosa neurons, which would contribute to their analgesic properties. Presynaptic mechanisms were likely in excitatory postsynaptic currents inhibition. Desflurane but not sevoflurane may have a hyperalgesic effect at subanesthetic doses.

Cav3.2 T‐type calcium channel mutation influences kindling‐induced thalamic neuronal firing patterns in Genetic Absence Epilepsy Rats From Strasbourg

Recent data indicate that amygdala kindling leads to significant changes in interictal neuronal firing patterns of thalamic reticular nucleus (TRN) neurons by decreasing the spontaneous firing rate and increasing burst firing in nonepileptic control (NEC) rats. Genetic Absence Epilepsy Rats From Strasbourg (GAERS) were resistant to these kindling-induced firing changes in TRN neurons, and are also resistant to the progression of kindling. We investigated whether a homozygous, missense, single nucleotide mutation (R1584P) in the Cav 3.2 T-type Ca2+ channel gene, which has been correlated with the expression of absence seizures in GAERS, influenced kindling progression and TRN firing patterns. Double-crossed (GAERS vs NEC; F2) rats that were homozygous for the Cav 3.2 mutation (PP) and those negative for the mutation (RR) were implanted with a stimulating electrode in the amygdala. Rats received a total of 30 kindling stimulations at their afterdischarge threshold current twice daily, and kindling progression was evaluated. Thereafter, the extracellular neuronal activity of TRN neurons was recorded in vivo under neuroleptanesthesia to investigate the influence of Cav 3.2 mutation on TRN firing patterns. We found that the R1584P mutation did not affect kindling progression in F2 crosses (P= 0.78). However, it influenced kindling-induced neuronal firing of TRN neurons. After 30 stimulations, RR rats exhibited a lower firing rate and a higher percentage of burst firing compared to PP rats. The decrease in firing frequency was correlated with the increase in the amount of burst firing in RR rats (R2 =0.497). Our findings suggest that mutation in Cav 3.2 T-type Ca2+ channels may play a role in the resistance to kindling-induced changes in TRN neurons to a low-frequency and high-percentage bursting pattern seen in association with the convulsive stages of amygdala kindling, but is not in itself enough to explain the resistance to kindling progression observed in GAERS.

Changes in Neuronal Representations of Consonants in the Ascending Auditory System and Their Role in Speech Recognition.

A fundamental task of the ascending auditory system is to produce representations that facilitate the recognition of complex sounds. This is particularly challenging in the context of acoustic variability, such as that between different talkers producing the same phoneme. These representations are transformed as information is propagated throughout the ascending auditory system from the inner ear to the auditory cortex (AI). Investigating these transformations and their role in speech recognition is key to understanding hearing impairment and the development of future clinical interventions. Here, we obtained neural responses to an extensive set of natural vowel-consonant-vowel phoneme sequences, each produced by multiple talkers, in three stages of the auditory processing pathway. Auditory nerve (AN) representations were simulated using a model of the peripheral auditory system and extracellular neuronal activity was recorded in the inferior colliculus (IC) and primary auditory cortex (AI) of anaesthetized guinea pigs. A classifier was developed to examine the efficacy of these representations for recognizing the speech sounds. Individual neurons convey progressively less information from AN to AI. Nonetheless, at the population level, representations are sufficiently rich to facilitate recognition of consonants with a high degree of accuracy at all stages indicating a progression from a dense, redundant representation to a sparse, distributed one. We examined the timescale of the neural code for consonant recognition and found that optimal timescales increase throughout the ascending auditory system from a few milliseconds in the periphery to several tens of milliseconds in the cortex. Despite these longer timescales, we found little evidence to suggest that representations up to the level of AI become increasingly invariant to across-talker differences. Instead, our results support the idea that the role of the subcortical auditory system is one of dimensionality expansion, which could provide a basis for flexible classification of arbitrary speech sounds.

Characteristics of sleep-active neurons in the medullary parafacial zone in rats

Growing evidence supports a role for the medullary parafacial zone in non-rapid eye movement (non-REM) sleep regulation. Cell-body specific lesions of the parafacial zone or disruption of its GABAergic/glycinergic transmission causes suppression of non-REM sleep, whereas, targeted activation of parafacial GABAergic/glycinergic neurons reduce sleep latency and increase non-REM sleep amount, bout duration, and cortical electroencephalogram (EEG) slow-wave activity. Parafacial GABAergic/glycinergic neurons also express sleep-associated c-fos immunoreactivity. Currently, it is not clear if parafacial neurons are non-REM sleep-active and/or REM sleep-active or play a role in the initiation or maintenance of non-REM sleep. We recorded extracellular discharge activity of parafacial neurons across the spontaneous sleep-waking cycle using microwire technique in freely behaving rats. Waking-, non-REM sleep-, and REM sleep-active neuronal groups were segregated by the ratios of their discharge rate changes during non-REM and REM sleep versus waking and non-REM sleep versus REM sleep. Parafacial neurons exhibited heterogeneity in sleep-waking discharge patterns, but 34 of 86 (40%) recorded neurons exhibited increased discharge rate during non-REM sleep compared to waking. These neurons also exhibited increased discharge prior to non-REM sleep onset, similar to median preoptic nucleus (MnPO) and ventrolateral preoptic area (VLPO) sleep-active neurons. However, unlike MnPO and VLPO sleep-active neurons, parafacial neurons were weakly-moderately sleep-active and exhibited a stable rather than decreasing discharge across sustained non-REM sleep episode. We show for the first time that the medullary parafacial zone contains non-REM sleep-active neurons. These neurons are likely functionally important brainstem compliments to the preoptic-hypothalamic sleep-promoting neuronal networks that underlie sleep onset and maintenance.

α-MSH Influences the Excitability of Feeding-Related Neurons in the Hypothalamus and Dorsal Vagal Complex of Rats.

Alpha-melanocyte-stimulating hormone (α-MSH) is processed from proopiomelanocortin (POMC) and acts on the melanocortin receptors, MC3 and MC4. α-MSH plays a key role in energy homeostasis. In the present study, to shed light on the mechanisms by which α-MSH exerts its anorectic effects, extracellular neuronal activity was recorded in the hypothalamus and the dorsal vagal complex (DVC) of anesthetized rats. We examined the impact of α-MSH on glucose-sensing neurons and gastric distension (GD) sensitive neurons. In the lateral hypothalamus (LHA), α-MSH inhibited 75.0% of the glucose-inhibited (GI) neurons. In the ventromedial nucleus (VMN), most glucose-sensitive neurons were glucose-excited (GE) neurons, which were mainly activated by α-MSH. In the paraventricular nucleus (PVN), α-MSH suppressed the majority of GI neurons and excited most GE neurons. In the DVC, among the 20 GI neurons examined for a response to α-MSH, 1 was activated, 16 were depressed, and 3 failed to respond. Nineteen of 24 GE neurons were activated by α-MSH administration. Additionally, among the 42 DVC neurons examined for responses to GD, 23 were excited (GD-EXC) and 19 were inhibited (GD-INH). Fifteen of 20 GD-EXC neurons were excited, whereas 11 out of 14 GD-INH neurons were suppressed by α-MSH. All these responses were abolished by pretreatment with the MC3/4R antagonist, SHU9119. In conclusion, the activity of glucose-sensitive neurons and GD-sensitive neurons in the hypothalamus and DVC can be modulated by α-MSH.

Neurons within the trigeminal mesencephalic nucleus encode for the kinematic parameters of the whisker pad macrovibrissae.

It has been recently shown in rats that spontaneous movements of whisker pad macrovibrissae elicited evoked responses in the trigeminal mesencephalic nucleus (Me5). In the present study, electrophysiological and neuroanatomical experiments were performed in anesthetized rats to evaluate whether, besides the whisker displacement per se, the Me5 neurons are also involved in encoding the kinematic properties of macrovibrissae movements, and also whether, as reported for the trigeminal ganglion, even within the Me5 nucleus exists a neuroanatomical representation of the whisker pad macrovibrissae. Extracellular electrical activity of single Me5 neurons was recorded before, during, and after mechanical deflection of the ipsilateral whisker pad macrovibrissae in different directions, and with different velocities and amplitudes. In several groups of animals, single or multiple injections of the tracer Dil were performed into the whisker pad of one side, in close proximity to the vibrissae follicles, in order to label the peripheral terminals of the Me5 neurons innervating the macrovibrissae (whisking‐neurons), and therefore, the respective perikaria within the nucleus. Results showed that: (1) the whisker pad macrovibrissae were represented in the medial‐caudal part of the Me5 nucleus by a single cluster of cells whose number seemed to match that of the macrovibrissae; (2) macrovibrissae mechanical deflection elicited significant responses in the Me5 whisking‐neurons, which were related to the direction, amplitude, and frequency of the applied deflection. The specific functional role of Me5 neurons involved in encoding proprioceptive information arising from the macrovibrissae movements is discussed within the framework of the whole trigeminal nuclei activities.