Rat Primary Somatosensory Cortex Research Articles

Laminar organization of neocortical activities during systemic anoxia

The neocortex is highly susceptible to metabolic dysfunction. When exposed to global ischemia or anoxia, it suffers a slowly propagating wave of collective neuronal depolarization that ultimately impairs its structure and function. While the molecular signature of anoxic depolarization (AD) is well documented, little is known about the brain states that precede and follow AD onset. Here, by means of multisite extracellular local field potentials and intracellular recordings from identified pyramidal cells, we investigated the laminar expression of cortical activities induced by transient anoxia in rat primary somatosensory cortex. Soon after the interruption of brain oxygenation, we observed a well-organized sequence of stereotyped activity patterns across all cortical layers. This sequence included an initial period of beta-gamma activity, rapidly replaced by delta-theta oscillations followed by a decline in all spontaneous activites, marking the entry into a sustained period of electrical silence. Intracellular recordings revealed that cortical pyramidal neurons were depolarized and highly active during high-frequency activity, became inactive and devoid of synaptic potentials during the isoelectric state, and showed subthreshold composite synaptic depolarizations during the low-frequency period. Contrasting with the strong temporal coherence of pre-AD activities along the vertical axis of the cortical column, the onset of AD was not uniform across layers. AD initially occurred in layer 5 or 6 and then propagated bidirectionally in the upward and downward direction. Conversely, the post-anoxic waves that indicated the repolarization of cortical neurons upon brain reoxygenation did not exhibit a specific spatio-temporal profile. Pyramidal neurons from AD initiation site had a more depolarized resting potential and higher spontaneous firing rate compared to superficial cortical cells. We also found that the propagation pattern of AD was reliably reproduced by focal injection of an inhibitor of sodium‑potassium ATPases, suggesting that cortical AD dynamics could reflect layer-dependent variations in cellular metabolic regulations.

Astrocytes Are Involved in the Effects of Ketamine on Synaptic Transmission in Rat Primary Somatosensory Cortex.

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used as a general anaesthetic. However, the mechanisms of analgesic/anaesthetic effects induced by ketamine are only partially understood. Previously, studies have demonstrated that various general anaesthetics affect the primary somatosensory cortex (S1), a potential target of general anaesthetics in the central nervous system. However, it is unknown if astrocyte activities affect ketamine's effects on information transmission in S1 pyramidal neurons. The whole-cell patch-clamp technique was employed to study the role of astrocytes in ketamine-induced anaesthetic actions. The whole-cell patch-clamp method was used to record the spontaneous postsynaptic currents (SPSCs) of rat S1 pyramidal neurons. We used the glia-selective inhibitor of the aconitase enzyme fluorocitrate (FC), to test if astrocyte activities alter the effects of ketamine on S1 pyramidal neurons. Ketamine lowered the SPSCs of rat S1 pyramidal neurons in a concentration-dependent manner at clinically relevant doses. The concentration-effect curve revealed that ketamine had an EC50 value of 462.1 M for suppressing SPSCs. In rat S1 pyramidal neurons, the glia-selective metabolic inhibitor fluorocitrate (FC), which inhibits the aconitase enzyme, lowered the amplitude and frequency of SPSCs. The inhibitory impact of ketamine on the amplitude and frequency of SPSCs was significantly amplified in the presence of FC. Astrocytes impact the effects of ketamine on pre- and postsynaptic components and play a role in synaptic transmission.

Lower jaw-to-forepaw rapid and delayed reorganization in the rat forepaw barrel subfield in primary somatosensory cortex.

We used the forepaw barrel subfield (FBS), that normally receives input from the forepaw skin surface, in rat primary somatosensory cortex as a model system to study rapid and delayed lower jaw-to-forepaw cortical reorganization. Single and multi-unit recording from FBS neurons was used to examine the FBS for the presence of "new" lower jaw input following deafferentations that include forelimb amputation, brachial plexus nerve cut, and brachial plexus anesthesia. The major findings are as follows: (1) immediately following forelimb deafferentations, new input from the lower jaw becomes expressed in the anterior FBS; (2) 7-27weeks after forelimb amputation, new input from the lower jaw is expressed in both anterior and posterior FBS; (3) evoked response latencies recorded in the deafferented FBS following electrical stimulation of the lower jaw skin surface are significantly longer in both rapid and delayed deafferents compared to control latencies for input from the forepaw to reach the FBS or for input from lower jaw to reach the LJBSF; (4) the longer latencies suggest that an additional relay site is imposed along the somatosensory pathway for lower jaw input to access the deafferented FBS. We conclude that different sources of input and different mechanisms underlie rapid and delayed reorganization in the FBS and suggest that these findings are relevant, as an initial step, for developing a rodent animal model to investigate phantom limb phenomena.

Sustained and potent analgesia with negligible side effects enabled by adaptive individualized granular stimulation in rat brainstem

Objectives. To clarify if an adaptive current stimulation protocol, in which current amplitude is modulated during continuous stimulation, provides better efficacy than constant current stimulation protocol with respect to analgesia caused by individualized stimulation in rat periaqueductal gray matter (PAG) /dorsal raphe nuclei (DRN). Approach. Ultrathin microelectrodes adapted for recording (n = 6) and stimulation (n = 16) were implanted in rat primary somatosensory cortex and PAG/DRN, respectively. In each animal included (n = 12), a subset of PAG/DRN microelectrodes (n = 1–3 per animal) was selected that on simultaneous stimulation blocked nociceptive withdrawal reflexes in awake unrestrained animals without noticeable side effects. Analgesic effects were subsequently assessed from both nociceptive withdrawal reflexes and intracortical pain-related responses on CO2 laser hind paw stimulation. The analgesic effects of adaptive current PAG/DRN stimulation comprising incremental increases of 5 μA/microelectrode (initial median current 30 μA/microelectrode) when effects declined were compared to the effects of constant current stimulation. Behavioral effects and brain state related changes were analyzed using quantitative movement analysis and electrocorticography (recorded on top of the dura mater), respectively. Tissue reactions and probe placement in PAG/DRN were assessed with immunohistochemistry. Main results. Powerful and sustained (4 h) analgesia was achieved with the adaptive current protocol within a rather wide area of PAG/DRN. Analgesic after-effects were seen for up to 30 min. Behavioral and brain state related side effects were minimal. Moreover, 6 weeks after implantation, there were no traces of bleedings, only small glial reactions and small but not statistically significant loss of neurons nearby indicating that the microelectrode stimulation employed is biocompatible. Significance. The results indicate that sustained and powerful analgesia with minimal side effects can be achieved by granular and individualized stimulation in PAG/DRN using an adaptive current stimulation protocol. This microelectrode technology and stimulation paradigm thus has the potential of providing a highly efficient and safe pain therapy.

Reducing Behavioral Detection Thresholds per Electrode via Synchronous, Spatially-Dependent Intracortical Microstimulation.

Intracortical microstimulation (ICMS) has shown promise in restoring quality of life to patients suffering from paralysis, specifically when used in the primary somatosensory cortex (S1). However, these benefits can be hampered by long-term degradation of electrode performance due to the brain’s foreign body response. Advances in microfabrication techniques have allowed for the development of neuroprostheses with subcellular electrodes, which are characterized by greater versatility and a less detrimental immune response during chronic use. These probes are hypothesized to enable more selective, higher-resolution stimulation of cortical tissue with long-term implants. However, microstimulation using physiologically relevant charges with these smaller-scale devices can damage electrode sites and reduce the efficacy of the overall device. Studies have shown promise in bypassing this limitation by spreading the stimulation charge between multiple channels in an implanted electrode array, but to our knowledge the usefulness of this strategy in laminar arrays with electrode sites spanning each layer of the cortex remains unexplored. To investigate the efficacy of simultaneous multi-channel ICMS in electrode arrays with stimulation sites spanning cortical depth, we implanted laminar electrode arrays in the primary somatosensory cortex of rats trained in a behavioral avoidance paradigm. By measuring detection thresholds, we were able to quantify improvements in ICMS performance using a simultaneous multi-channel stimulation paradigm. The charge required per site to elicit detection thresholds was halved when stimulating from two adjacent electrode sites, although the overall charge used by the implant was increased. This reduction in threshold charge was more pronounced when stimulating with more than two channels and lessened with greater distance between stimulating channels. Our findings suggest that these improvements are based on the synchronicity and polarity of each stimulus, leading us to conclude that these improvements in stimulation efficiency per electrode are due to charge summation as opposed to a summation of neural responses to stimulation. Additionally, the per-site charge reductions are seen regardless of the cortical depth of each utilized channel. This evocation of physiological detection thresholds with lower stimulation currents per electrode site has implications for the feasibility of stimulation regimes in future advanced neuroprosthetic devices, which could benefit from reducing the charge output per site.

High-frequency burst spiking in layer 5 thick-tufted pyramids of rat primary somatosensory cortex encodes exploratory touch

Diversity of cell-types that collectively shape the cortical microcircuit ensures the necessary computational richness to orchestrate a wide variety of behaviors. The information content embedded in spiking activity of identified cell-types remain unclear to a large extent. Here, we recorded spike responses upon whisker touch of anatomically identified excitatory cell-types in primary somatosensory cortex in naive, untrained rats. We find major differences across layers and cell-types. The temporal structure of spontaneous spiking contains high-frequency bursts (≥100 Hz) in all morphological cell-types but a significant increase upon whisker touch is restricted to layer L5 thick-tufted pyramids (L5tts) and thus provides a distinct neurophysiological signature. We find that whisker touch can also be decoded from L5tt bursting, but not from other cell-types. We observed high-frequency bursts in L5tts projecting to different subcortical regions, including thalamus, midbrain and brainstem. We conclude that bursts in L5tts allow accurate coding and decoding of exploratory whisker touch.

Multi-session delivery of synchronous rTMS and sensory stimulation induces long-term plasticity

BackgroundCombining training or sensory stimulation with non-invasive brain stimulation has shown to improve performance in healthy subjects and improve brain function in patients after brain injury. However, the plasticity mechanisms and the optimal parameters to induce long-term and sustainable enhanced performance remain unknown. ObjectiveThis work was designed to identify the protocols of which combining sensory stimulation with repetitive transcranial magnetic stimulation (rTMS) will facilitate the greatest changes in fMRI activation maps in the rat's primary somatosensory cortex (S1). MethodsSeveral protocols of combining forepaw electrical stimulation with rTMS were tested, including a single stimulation session compared to multiple, daily stimulation sessions, as well as synchronous and asynchronous delivery of both modalities. High-resolution fMRI was used to determine how pairing sensory stimulation with rTMS induced short and long-term plasticity in the rat S1. ResultsAll groups that received a single session of rTMS showed short-term increases in S1 activity, but these increases did not last three days after the session. The group that received a stimulation protocol of 10 Hz forepaw stimulation that was delivered simultaneously with 10 Hz rTMS for five consecutive days demonstrated the greatest increases in the extent of the evoked fMRI responses compared to groups that received other stimulation protocols. ConclusionsOur results provide direct indication that pairing peripheral stimulation with rTMS induces long-term plasticity, and this phenomenon appears to follow a time-dependent plasticity mechanism. These results will be important to lead the design of new training and rehabilitation paradigms and training towards achieving maximal performance in healthy subjects.

Removal of a compressive mass causes a transient disruption of blood-brain barrier but a long-term recovery of spiny stellate neurons in the rat somatosensory cortex.

In the cranial cavity, a space-occupying mass such as epidural hematoma usually leads to compression of brain. Removal of a large compressive mass under the cranial vault is critical to the patients. The purpose of this study was to examine whether and to what extent epidural decompression of the rat primary somatosensory cortex affects the underlying microvessels, spiny stellate neurons and their afferent fibers. Rats received epidural decompression with preceding 1-week compression by implantation of a bead. The thickness of cortex was measured using brain coronal sections. The permeability of blood-brain barrier (BBB) was assessed by Evans Blue and immunoglobulin G extravasation. The dendrites and dendritic spines of the spiny stellate neurons were revealed by Golgi-Cox staining and analyzed. In addition, the thalamocortical afferent (TCA) fibers in the cortex were illustrated using anterograde tracing and examined. The cortex gradually regained its thickness over time and became comparable to the sham group at 3 days after decompression. Although the diameter of cortical microvessels were unaltered, a transient disruption of the BBB was observed at 6 hours and 1 day after decompression. Nevertheless, no brain edema was detected. In contrast, the dendrites and dendritic spines of the spiny stellate neurons and the TCA fibers were markedly restored from 2 weeks to 3 months after decompression. Epidural decompression caused a breakdown of the BBB, which was early-occurring and short-lasting. In contrast, epidural decompression facilitated a late-onset and prolonged recovery of the spiny stellate neurons and their afferent fibers.

An Experimental Animal Model that Parallels Neurosensory Assessments of Concussion.

Tactile-based quantitative sensory assessments have proven successful in differentiating concussed vs. non-concussed individuals. One potential advantage of this methodology is that an experimental animal model can be used to obtain neurophysiological recordings of the neural activity in the somatosensory cortex evoked in response to the same tactile stimuli that are used in human sensory assessments and establish parallels between various metrics of stimulus-evoked cortical activity and perception of the stimulus attributes. Stimulus-evoked neural activity was recorded via extracellular microelectrodes in rat primary somatosensory cortex (S1) in response to vibrotactile stimuli that are used in two particular human sensory assessments (reaction time (RT) and amplitude discrimination). Experiments were conducted on healthy control and brain-injured (BI) rats. Similar to the effects of mild traumatic brain injuries (mTBI) on human neurosensory assessments, comparable experimentally induced brain injuries in rats resulted in the following: (1) elevation of S1 responsivity to vibrotactile stimulation that depended nonlinearly on stimulus amplitude, significantly reducing its capacity to discriminate between stimuli of different amplitudes; (2) 50% reduction in S1 signal-to-noise ratios, which can be expected to contribute to elevation of RT in BI rats; and (3) 60% increase in intertrial variability of S1 responses to vibrotactile stimulation, which can be expected to contribute to elevation of RT variability in BI rats. The results demonstrate suggestive similarities between neurophysiological observations made in the experimental rat mTBI model and observations made in post-concussion individuals with regard to three sensory assessment metrics (amplitude discrimination, RT, and RT variability). This is the first successful model that demonstrates that perceptual metrics obtained from human individuals are impacted by mTBI in a manner consistent with neurophysiological observations obtained from rat S1.

Неравномерное распределение мембран астроцитов по слоям первичной соматосенсорной коры мозга крыс

Astrocytes are the main glial cells maintaining water-electrolyte and energy balance in the brain. Today, astroglia is also believed to take a direct part in the regulation of synaptic transmission and in enabling synchronous operation of neurons at large distances. Astrocytes fulfil their functions through numerous processes that penetrate the entire neuropil. The authors believe that changes in the astrocyte membrane surface area per unit volume of neuropil directly reflect changes in the intensity of the astrocyte–neuron interaction. Strengthening or weakening of astrocyte regulation, undoubtedly, affect the functioning of neural circuits. Nevertheless, in spite of the growing popularity of research into the glia–neuron relations, this aspect remains insufficiently studied when it comes to the cerebral cortex. The purpose of this study was to layer-by-layer determine the astrocyte membrane surface per unit volume in the neuropil of the rat primary somatosensory cortex. The research was conducted on samples of the primary somatosensory cortex obtained from 5 white male rats (P60–80). After immune labeling against astrocytic marker S100B using the pre-embedding method, the samples were prepared for transmission electron microscopy according to the standard technique. In total, 250 electron micrographs were obtained for each layer of the primary somatosensory cortex, which were then used to determine the astrocyte membrane surface area per unit volume in the neuropil by means of the random secant method. The research found that this indicator is the minimum in the first and maximum in the fifth layers of the cortical column. In addition, the article discusses the possible functional consequences of uneven distribution of astrocytic membranes in the neocortex.

Structural and functional organization of the lower jaw barrel subfield in rat primary somatosensory cortex.

Barrel subfields in rodent primary somatosensory cortex (SI) are important model systems for studying cortical organization and reorganization. During cortical reorganization that follows limb deafferentation, neurons in deafferented forelimb SI become responsive to previously unexpressed inputs from the lower jaw. Although the lower jaw barrel subfield (LJBSF) is a likely source of the input, this subfield has received little attention. Our aim was to describe the structural and functional organization of the normal LJBSF. To investigate LJBSF organization, a nomenclature for lower jaw skin surface was developed, cytochrome oxidase (CO) was used to label flattened-cut LJBSF sections, microelectrodes were used to map the lower jaw skin surface representation in SI, and electrolytic lesions, recovered from electrode penetrations, were used to align the physiological map to the underlying barrel map. LJBSF is a tear-shaped subfield containing approximately 24 barrels, arranged in eight mediolateral rows and a barrel-free zone capping the anterior border. The representation of the lower jaw skin consisting of chin vibrissae and microvibrissae embedded in common fur is somatotopically organized in a single map in the contralateral SI. This physiological map shows that the activity from the vibrissae aligns with the CO-staining of the underlying LJBSF. LJBSF barrels receive topographically ordered barrel-specific input from individual vibrissa and microvibrissae in the lower jaw but not from trident whiskers. The barrel-free zone receives topographically ordered input from the lower lip. These data demonstrating that the LJBSF is a highly organized subfield are essential for understanding its possible role in cortical reorganization.

Effect of mild traumatic brain injury on spontaneous activity of rat primary somatosensory cortex and its responsivity to vibrotactile stimulation

While it has been previously demonstrated that concussion severity can be assessed using sensory tests of cortical functionality, the underlying neural mechanisms affected by concussion are still poorly understood. By using an animal model, it is possible to directly observe the neurophysiological effects of concussion, and thus shed light on the underlying changes in cortical functionality. In order to assess the effects of a single concussion, we recorded spike discharge activity of neurons in the rat primary somatosensory cortex prior to as well as 6-12hr and 78-86hr after a mild weight-drop impact-acceleration closed-head trauma. During the 6-12hr post-impact period, cortical spontaneous activity was elevated by 40% compared to the healthy control state, but its responsivity to vibrotactile stimulation was not significantly affected. However, the responsivity to vibrotactile stimulation did decline in the 78-86hr post-impact period. Also during this period, spontaneous activity in the middle and upper cortical layers was reduced by 35% below the healthy control state, but it remained high in the deep layers. We also recorded somatosensory cortical activity 6-12hr after delivering a second head trauma, identical to the one delivered 72hr prior. Although the two impacts mechanically were the same, the neurophysiological effect of the second impact was very different from that observed after the first impact: both the stimulus-evoked response and spontaneous activity were significantly reduced as compared to the same time period after the first impact. These findings demonstrate that mTBI alters the functional state of the somatosensory cortex in a post-injury time-dependent manner.

Flexible Electrocorticography Electrode Array for Epileptiform Electrical Activity Recording under Glutamate and GABA Modulation on the Primary Somatosensory Cortex of Rats.

Epilepsy is a common neurological disorder. There is still a lack of methods to accurately detect cortical activity and locate lesions. In this work, a flexible electrocorticography (ECoG) electrode array based on polydimethylsiloxane (PDMS)-parylene was fabricated to detect epileptiform activity under glutamate (Glu) and gamma-aminobutyric acid (GABA) modulation on primary somatosensory cortex of rats. The electrode with a thickness of 20 μm has good flexibility to establish reliable contact with the cortex. Fourteen recording sites with a diameter of 60 μm are modified by electroplating platinum black nanoparticles, which effectively improve the performance with lower impedance, obtaining a sensitive sensing interface. The electrode enables real-time capturing changes in neural activity under drug modulation. Under Glu modulation, neuronal populations showed abnormal excitability, manifested as hypsarrhythmia rhythm and continuous or periodic spike wave epileptiform activity, with power increasing significantly. Under GABA modulation, the excitement was inhibited, with amplitude and power reduced to normal. The flexible ECoG electrode array could monitor cortical activity, providing us with an effective tool for further studying epilepsy and locating lesions.

Effects of basal forebrain stimulation on the vibrotactile responses of neurons from the hindpaw representation in the rat SI cortex.

Basal forebrain (BF) cholinergic system is important for attention and modulates sensory processing. We focused on the hindpaw representation in rat primary somatosensory cortex (S1), which receives inputs related to mechanoreceptors identical to those in human glabrous skin. Spike data were recorded from S1 tactile neurons (n = 87) with (ON condition: 0.5-ms bipolar current pulses at 100Hz; amplitude 50μA, duration 0.5s at each trial) and without (OFF condition) electrical stimulation of BF in anesthetized rats. We expected that prior activation of BF would induce changes in the vibrotactile responses of neurons during sinusoidal (5, 40, and 250Hz) mechanical stimulation of the glabrous skin. The experiment consisted of sequential OFF-ON conditions in two-time blocks separated by 30min to test possible remaining effects. Average firing rates (AFRs) and vector strengths of spike phases (VS) were analyzed for different neuron types [regular spiking (RS) and fast spiking (FS)] in different cortical layers (III-VI). Immediate effect of BF activation was only significant by increasing synchronization to 5-Hz vibrotactile stimulus within the second block. Regardless of frequency, ON-OFF paired VS differences were significantly higher in the second block compared to the first, more prominent for RS neurons, and in general for neurons in layers III and VI. No such effects could be found on AFRs. The results suggest that cholinergic activation induces some changes in the hindpaw area, enabling relatively higher increases in synchronization to vibrotactile inputs with subsequent BF modulation. In addition, this modulation depends on neuron type and layer, which may be related to detailed projection pattern from BF.

Environmental enrichment enhances post-ischemic cerebral blood flow and functional hyperemia in the ipsilesional somatosensory cortex

Environmental enrichment has been reported to promote functional recovery in an ischemic stroke. However, the underlying mechanism remains unclear. This study aimed to investigate the effect of environmental enrichment treatment on post-ischemic cerebral blood flow and functional hyperemia in the ipsilesional primary somatosensory cortex of rats. With laser speckle imaging, we were able to monitor the resting cerebral blood flow alteration in the middle cerebral artery occlusion model. Both 3- and 28-day post-ischemic infarct volumes were then examined with triphenyltetrazolium chloride and cresyl violet staining, respectively. We found that an exposure to environmental enrichment was associated with higher post-ischemic cerebral blood flow and less brain tissue loss in the ipsilesional primary somatosensory cortex compared with the standard cage environment. Furthermore, environmental enrichment also enhanced the cerebral blood flow response to whisker stimulation in the ipsilesional barrel cortex when measured 28 days after the middle cerebral artery occlusion. Together, the data suggested that an exposure to environmental enrichment promoted the restoration of cerebral blood flow in the ipsilesional cortex and contributed to a better coupling between functional activation and cerebral blood flow change, which might be the possible mechanisms underlying the neuroprotective effects of EE after ischemia.

Repetitive microstimulation in rat primary somatosensory cortex (SI) strengthens the connection between homotopic sites in the opposite SI and leads to expression of previously ineffective input from the ipsilateral forelimb

The primary somatosensory cortex (SI) receives input from the contralateral forelimb and projects to homotopic sites in the opposite SI. Since homotopic sites in SI are linked by a callosal pathway, we proposed that repetitive intracortical microstimulation (ICMSr) of neurons in layer V of SI forelimb cortex would increase spike firing in the opposite SI cortex thereby strengthening the callosal pathway sufficiently to allow normally ineffective stimuli from the ipsilateral forelimb to excite cells in the ipsilateral SI. The forelimb representation in SI in one hemisphere was mapped using mechanical and electrical stimulation of the contralateral forelimb, a homotopic site was similarly identified in the opposite SI, the presence of ipsilateral peripheral input was tested in both homotopic sites, and ICMS was used to establish an interhemispheric connection between the two homotopic recording sites. The major findings are: (1) each homotopic forelimb site in SI initially received short latency input only from the contralateral forelimb; (2) homotopic sites in layer V in each SI were interconnected by a callosal pathway; (3) ICMSr delivered to layer V of the homotopic SI in one hemisphere generally increased evoked response spike firing in layer V in the opposite homotopic site; (4) increased spike firing was often followed by the expression of a longer latency normally ineffective input from the ipsilateral forelimb; (5) these longer latency ipsilateral responses are consistent with a delay time sufficient to account for travel across the callosal pathway; (6) increased spike firing and the resulting ipsilateral peripheral input were also corroborated using in-vivo intracellular recording; and (7) inactivation of the stimulating site in SI by lidocaine injection or local surface cooling abolished the ipsilateral response, suggesting that the ipsilateral response was very likely relayed across the callosal pathway. These results suggest that repetitive microstimulation can do more than expand receptive fields in the territory adjacent to the stimulating electrode but in addition can also alter receptive fields in homotopic sites in the opposite SI to bring about the expression of previously ineffective input from the ipsilateral forelimb.

Telemetry-controlled simultaneous stimulation-and-recording device (SRD) to study interhemispheric cortical circuits in rat primary somatosensory (SI) cortex

BackgroundA growing need exists for neuroscience platforms that can perform simultaneous chronic recording and stimulation of neural tissue in animal models in a telemetry-controlled fashion with signal processing for analysis of the chronic recording data and external triggering capability. We describe the system design, testing, evaluation, and implementation of a wireless simultaneous stimulation-and-recording device (SRD) for modulating cortical circuits in physiologically identified sites in primary somatosensory (SI) cortex in awake-behaving and freely-moving rats. The SRD was developed using low-cost electronic components and open-source software. The function of the SRD was assessed by bench and in-vivo testing.ResultsThe SRD recorded spontaneous spiking and bursting neuronal activity, evoked responses to programmed intracortical microstimulation (ICMS) delivered internally by the SRD, and evoked responses to external peripheral forelimb stimulation.ConclusionsThe SRD is capable of wireless stimulation and recording on a predetermined schedule or can be wirelessly synchronized with external input as would be required in behavioral testing prior to, during, and following ICMS.

Probing activation-induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex.

Knowledge about biochemical processes is a prerequisite for a better understanding of mechanisms underlying brain activity. 1 H functional magnetic resonance spectroscopy (1 H-fMRS) at high magnetic fields allows for the non-invasive measurement of metabolic changes during brain activation. Optogenetics, on the other hand, has revolutionized the field of neuroscience. It was previously coupled with functional magnetic resonance imaging (fMRI) techniques in rodents enabling population-specific targeting of cells, investigating brain networks with unprecedented in vivo precision. The coupling of optogenetics and 1 H-fMRS is expected to enhance the specificity of metabolic readouts to validate neuro-energetic theories underlying brain activity. To date, the feasibility of combining optogenetic stimulation with fMRS has not been explored. We used green laser stimulation delivered through an optical fiber implanted superficially above the primary somatosensory forelimb cortex (S1FL) of rats expressing the C1V1 opsin in excitatory neurons. A protocol for the acquisition of functional 1 H MR spectra upon optogenetic stimulation without craniotomy-induced artefacts was established. Quantification of metabolite concentrations in S1FL upon optogenetic and electrical forepaw stimulation demonstrated significantly increased glutamate levels (+8.8% and +9.9%, p<0.05 respectively), which were compensated by decreased glutamine levels (-17% and -18%, p<0.05 respectively). Our results demonstrate for the first time the feasibility of combining optogenetic control and functional MR spectroscopy (o-fMRS) in the rat somatosensory cortex, opening new possibilities for monitoring the energetic demands of specific cell populations and for exploring the underpinnings of energy metabolism during brain activity. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

Cortical Pain Processing in the Rat Anterior Cingulate Cortex and Primary Somatosensory Cortex

Pain is a complex multidimensional experience encompassing sensory-discriminative, affective-motivational and cognitive-emotional components mediated by different neural mechanisms. Investigations of neurophysiological signals from simultaneous recordings of two or more cortical circuits may reveal important circuit mechanisms on cortical pain processing. The anterior cingulate cortex (ACC) and primary somatosensory cortex (S1) represent two most important cortical circuits related to sensory and affective processing of pain. Here, we recorded in vivo extracellular activity of the ACC and S1 simultaneously from male adult Sprague-Dale rats (n = 5), while repetitive noxious laser stimulations were delivered to animalÕs hindpaw during pain experiments. We identified spontaneous pain-like events based on stereotyped pain behaviors in rats. We further conducted systematic analyses of spike and local field potential (LFP) recordings from both ACC and S1 during evoked and spontaneous pain episodes. From LFP recordings, we found stronger phase-amplitude coupling (theta phase vs. gamma amplitude) in the S1 than the ACC (n = 10 sessions), in both evoked (p = 0.058) and spontaneous pain-like behaviors (p = 0.017, paired signed rank test). In addition, pain-modulated ACC and S1 neuronal firing correlated with the amplitude of stimulus-induced event-related potentials (ERPs) during evoked pain episodes. We further designed statistical and machine learning methods to detect pain signals by integrating ACC and S1 ensemble spikes and LFPs. Together, these results reveal differential coding roles between the ACC and S1 in cortical pain processing, as well as point to distinct neural mechanisms between evoked and putative spontaneous pain at both LFP and cellular levels.

Temporal cueing enhances neuronal and behavioral discrimination performance in rat whisker system

Since sensory systems operate with a finite quantity of processing resources, an animal would benefit from prioritizing processing of sensory stimuli within a time window that is expected to provide key information. This behavioral manifestation of such prioritization is known as attention. Here, we investigate attention with temporal cueing and its neuronal correlates in the rat primary vibrissal somatosensory (vS1) cortex. Rats were trained in a simple whisker vibration detection task. A vibration was presented at one of two spatial locations (left or right), sometimes after an unknown time interval and sometimes after receiving an auditory cue. The auditory cue provided temporal but not spatial information about the vibration. We found that for all rats ( n = 6), the auditory cue consistently enhanced detection of the vibration stimulus. Neuronal activity in vS1 cortex reflected the observed behavioral enhancement from temporal cueing with single units responded differentially to the whisker vibration stimulus when it was temporally predicted by the auditory cue, exhibiting an enhanced signal-to-noise ratio. Our findings indicate that rats are capable of prioritizing processing within a specified time window and provide evidence that the primary sensory cortex may participate in the temporal allocation of resources. NEW & NOTEWORTHY We demonstrate a novel paradigm of temporal cueing in rats. In a two-alternative whisker detection task, an auditory cue provided information about the timing of the stimulus but not the correct choice. In the presence of cue, detection was faster and more accurate, and neuronal activity from the primary somatosensory cortex revealed enhanced representation of vibrations. These results thus establish the rat as an alternative model organism to primates for studying temporal attention.