Rat Primary Somatosensory Cortex Research Articles

Effect of chronic morphine exposure on response properties of rat barrel cortex neurons

Chronic exposure to morphine can impair performance in tasks which need sensory processing. Using single unit recordings we investigate the effect of chronic morphine exposure on the firing properties of neurons in layers IV and V of the whisker-related area of rat primary somatosensory cortex. In urethane-anesthetized animals, neuronal activity was recorded in response to principal and adjacent whisker deflections either stimulated independently or in a conditioning test paradigm. A condition test ratio (CTR) was calculated for assessing the inhibitory receptive field. In layer IV, chronic morphine treatment did not change the spontaneous discharge activity. On responses to principal and adjacent whisker deflections did not show any significant changes following chronic morphine exposure. The magnitude Off responses to adjacent whisker deflection decreased while its response latency increased. In addition, there was a significant increase in the latency of Off responses to principal whisker deflection. CTR did not change significantly following morphine exposure. Layer V neurons, on the other hand, did not show any significant changes in their spontaneous activity or their evoked responses following morphine exposure. Our results suggest that chronic morphine exposure has a subtle modulatory effect on response properties of neurons in barrel cortex.

Quality of coding of whisker deflection by an ensemble of neurons in rat primary somatosensory cortex increases with postnatal development

Quality of coding of whisker deflection by an ensemble of neurons in rat primary somatosensory cortex increases with postnatal development

Shifting and scaling adaptation to dynamic stimuli in somatosensory cortex

Recent reports have shown that responses of midbrain neurons in the guinea pig rapidly shift the dynamic range of their responses to track changes in the statistics of ongoing sound-level distributions. This results in an increased coding accuracy for the most commonly occurring stimulus intensities. To investigate whether this type of adaptation might also be found in other sensory modalities, we characterized the intensity-response functions of neurons in rat primary somatosensory cortex (S1) to continuous sinusoidal vibration of the whiskers with amplitudes that were changed every 40 ms. Vibration amplitudes were selected randomly such that there was an 80% chance for the amplitude to be drawn from a relatively narrow 'high-probability region' (HPR). Stimulus mean and variance were then manipulated by shifting or widening the HPR. We found that rat S1 neurons adapt to shifts of the HPR mainly by shifting their thresholds, and to changes in HPR width by changing the slope of their rate-level curves. Using realistic single-neuron models, we go on to show that after-hyperpolarizing currents, such as those carried by K(Ca)(2+) channels, may be responsible for the threshold shifts, but not the slope changes.

Neuronal Activity in the Primary Somatosensory Thalamocortical Loop Is Modulated by Reward Contingency during Tactile Discrimination

Delayed-response sensory discrimination is believed to require primary sensory thalamus and cortex for early stimulus identification and higher-order forebrain regions for the late association of stimuli with rewarded motor responses. Here we investigate neuronal responses in the rat primary somatosensory cortex (S1) and ventral posterior medial nucleus of the thalamus (VPM) during a tactile discrimination task that requires animals to associate two different tactile stimuli with two corresponding choices of spatial trajectory to be rewarded. To manipulate reward expectation, neuronal activity observed under regular reward contingency (CR) was compared with neuronal activity recorded during freely rewarded (FR) trials, in which animals obtained reward regardless of their choice of spatial trajectory. Across-trial firing rates of S1 and VPM neurons varied according to the reward contingency of the task. Analysis of neuronal ensemble activity by an artificial neural network showed that stimulus-related information in S1 and VPM increased from stimulus sampling to reward delivery in CR trials but decreased to chance levels when animals performed FR trials, when stimulus discrimination was irrelevant for task execution. Neuronal ensemble activity in VPM was only correlated with task performance during stimulus presentation. In contrast, S1 neuronal activity was highly correlated with task performance long after stimulus removal, a relationship that peaked during the 300 ms that preceded reward delivery. Together, our results indicate that neuronal activity in the primary somatosensory thalamocortical loop is strongly modulated by reward contingency.

Observing without disturbing: how different cortical neuron classes represent tactile stimuli

Observing without disturbing: how different cortical neuron classes represent tactile stimuli

Layer‐ and cell‐type‐specific suprathreshold stimulus representation in rat primary somatosensory cortex

Sensory stimuli are encoded differently across cortical layers and it is unknown how response characteristics relate to the morphological identity of responding cells. We therefore juxtasomally recorded action potential (AP) patterns from excitatory cells in layer (L) 2/3, L4, L5 and L6 of rat barrel cortex in response to a standard stimulus (e.g. repeated deflection of single whiskers in the caudal direction). Subsequent single-cell filling with biocytin allowed for post hoc identification of recorded cells. We report three major conclusions. First, sensory-evoked responses were layer- and cell-type-specific but always < 1 AP per stimulus, indicating low AP rates for the entire cortical column. Second, response latencies from L4, L5B and L6 were comparable and thus a whisker deflection is initially represented simultaneously in these layers. Finally, L5 thick-tufted cells dominated the cortical AP output following sensory stimulation, suggesting that these cells could direct sensory guided behaviours.

Suppressed Neuronal Activity and Concurrent Arteriolar Vasoconstriction May Explain Negative Blood Oxygenation Level-Dependent Signal

Synaptic transmission initiates a cascade of signal transduction events that couple neuronal activity to local changes in blood flow and oxygenation. Although a number of vasoactive molecules and specific cell types have been implicated, the transformation of stimulus-induced activation of neuronal circuits to hemodynamic changes is still unclear. We use somatosensory stimulation and a suite of in vivo imaging tools to study neurovascular coupling in rat primary somatosensory cortex. Our stimulus evoked a central region of net neuronal depolarization surrounded by net hyperpolarization. Hemodynamic measurements revealed that predominant depolarization corresponded to an increase in oxygenation, whereas predominant hyperpolarization corresponded to a decrease in oxygenation. On the microscopic level of single surface arterioles, the response was composed of a combination of dilatory and constrictive phases. Critically, the relative strength of vasoconstriction covaried with the relative strength of oxygenation decrease and neuronal hyperpolarization. These results suggest that a neuronal inhibition and concurrent arteriolar vasoconstriction correspond to a decrease in blood oxygenation, which would be consistent with a negative blood oxygenation level-dependent functional magnetic resonance imaging signal.

Detection psychophysics of intracortical microstimulation in rat primary somatosensory cortex

A problem of purposeful intracortical microstimulation is the long duration of neuronal integration time and the associated complex temporal interactions of effects to individual pulses in trains. Here we investigated the effects of repetitive stimuli on perception. We trained head-restraint rats to indicate the detection of cortical microstimulation in infragranular layers of barrel cortex. Three stimulus parameters: stimulus intensity, number of pulses and frequency were varied, and psychometric detection curves were assessed using the method of constant stimuli. The average psychophysical threshold of single pulses was 2.0 nC--a measure very close to what has been found earlier for the evocation of short-latency action potentials in neurons near the stimulation electrode. Detection of single-pulse stimulation always saturated at probabilities of about 0.8. In contrast, repetitive stimuli gave rise to lower thresholds (by a factor of two at 15 pulses, 320 Hz), and to saturation at probabilities close to 1. Interestingly, a large fraction of these perceptual benefits was observed already with double pulses. Moreover, the perceptual efficacy of individual pulses was higher using double pulses compared with longer sequences, i.e. double pulses were detected better than expected from the assumption of independence of single-pulse effects, while trains of 15 pulses fell well short of this expectation. The present results thus point to double-pulse stimulation as an optimal choice when trading economic stimulation against optimizing of the percept.

Spike Timing-Dependent Synaptic Depression in theIn VivoBarrel Cortex of the Rat

Spike timing-dependent plasticity (STDP) is a computationally powerful form of plasticity in which synapses are strengthened or weakened according to the temporal order and precise millisecond-scale delay between presynaptic and postsynaptic spiking activity. STDP is readily observed in vitro, but evidence for STDP in vivo is scarce. Here, we studied spike timing-dependent synaptic depression in single putative pyramidal neurons of the rat primary somatosensory cortex (S1) in vivo, using two techniques. First, we recorded extracellularly from layer 2/3 (L2/3) and L5 neurons, and paired spontaneous action potentials (postsynaptic spikes) with subsequent subthreshold deflection of one whisker (to drive presynaptic afferents to the recorded neuron) to produce "post-leading-pre" spike pairings at known delays. Short delay pairings (<17 ms) resulted in a significant decrease of the extracellular spiking response specific to the paired whisker, consistent with spike timing-dependent synaptic depression. Second, in whole-cell recordings from neurons in L2/3, we paired postsynaptic spikes elicited by direct-current injection with subthreshold whisker deflection to drive presynaptic afferents to the recorded neuron at precise temporal delays. Post-leading-pre pairing (<33 ms delay) decreased the slope and amplitude of the PSP evoked by the paired whisker, whereas "pre-leading-post" delays failed to produce depression, and sometimes produced potentiation of whisker-evoked PSPs. These results demonstrate that spike timing-dependent synaptic depression occurs in S1 in vivo, and is therefore a plausible plasticity mechanism in the sensory cortex.

A remote control training system for rat navigation in complicated environment

A remote control system has been developed to deliver stimuli into the rat brain through a wireless micro-stimulator for animal behavior training. The system consists of the following main components: an integrated PC control program, a transmitter and a receiver based on Bluetooth (BT) modules, a stimulator controlled by C8051 microprocessor, as well as an operant chamber and an eight-arm radial maze. The micro-stimulator is featured with its changeable amplitude of pulse output for both constant-voltage and constant-current mode, which provides an easy way to set the proper suitable stimulation intensity for different training. The system has been used in behavior experiments for monitoring and recording bar-pressing in the operant chamber, contriolling rat roaming in the eight-arm maze, as well as navigating rats through a 3D obstacle route. The results indicated that the system worked stably and that the stimulation was effective for different types of rat behavior controls. In addition, the results showed that stimulation in the whisker barrel region of rat primary somatosensory cortex (SI) acted like a cue. The animals can be trained to take different desired turns upon the association between the SI cue stimulation and the reward stimulation in the medial forebrain bundle (MFB).

Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex

Background: Mechanisms of neurovascular coupling—the relationship between neuronal chemoelectrical activity and compensatory metabolic and hemodynamic changes—appear to be preserved across species from rats to humans despite differences in scale. However, previous work suggests that the highly cellular dense mouse somatosensory cortex has different functional hemodynamic changes compared to other species. Methods: We developed novel hardware and software for 2-dimensional optical spectroscopy (2DOS). Optical changes at four simultaneously recorded wavelengths were measured in both rat and mouse primary somatosensory cortex (S1) evoked by forepaw stimulation to create four spectral maps. The spectral maps were converted to maps of deoxy-, oxy-, and total-hemoglobin (HbR, HbO, and HbT) concentration changes using the modified Beer–Lambert law and phantom HbR and HbO absorption spectra. Results: Functional hemodynamics were different in mouse versus rat neocortex. On average, hemodynamics were as expected in rat primary somatosensory cortex (S1): the fractional change in the log of HbT concentration increased monophasically 2 s after stimulus, whereas HbO changes mirrored HbR changes, with HbO showing a small initial dip at 0.5 s followed by a large increase 3.0 s post stimulus. In contrast, mouse S1 showed a novel type of stimulus-evoked hemodynamic response, with prolonged, concurrent, monophasic increases in HbR and HbT and a parallel decrease in HbO that all peaked 3.5–4.5 s post stimulus onset. For rats, at any given time point, the average size and shape of HbO and HbR forepaw maps were the same, whereas surface veins distorted the shape of the HbT map. For mice, HbO, HbR, and HbT forepaw maps were generally the same size and shape at any post-stimulus time point. Conclusions: 2DOS using image splitting optics is feasible across species for brain mapping and quantifying the map topography of cortical hemodynamics. These results suggest that during physiologic stimulation, different species and/or cortical architecture may give rise to different hemodynamic changes during neurovascular coupling.

Differentiating hemodynamic responses in rat primary somatosensory cortex during non-noxious and noxious electrical stimulation by optical imaging

Nociception in the primary somatosensory (S1) cortex remains in need of further elucidation. The spatiotemporal comparison on changes of the cerebral blood volume evoked by graded peripheral electrical stimulation was performed in rat contralateral somatosensory cortex with optical intrinsic signal imaging (OISI, optical reflectance at 550 nm). Non-noxious electrical stimulus was applied with 5 Hz pulses (0.5 ms peak duration) for 2 s at the threshold current for muscle twitch, while noxious stimulus was delivered at currents of 10× and 20× amplitude of the predetermined threshold. Although the dimensions of peak response defined in the spatial domain (cerebral blood volume increase) in the S1 cortex presented no significant difference under non-/noxious stimuli, its early response component (about 1 s after stimulation onset) revealed by OISI technique was suggested to differentiate the loci of activated cortical region due to different stimulation in this study. The magnitude and duration of the optical intrinsic signal (OIS) response was found increasing with the varying stimulus intensity. Regions activated by the delivery of a noxious stimulus were surrounded by a ring of inverted optical intrinsic signal, the amplitude of that was inversely proportional to the strength of the optical signal attributable to activation. Intense stimuli significantly augmented the inverted optical signal in magnitude and spatial extent. These results indicated that noxious stimulation evoked different response patterns in the contralateral S1 cortex. The magnitude-dependent inverted optical signal might contribute to the differentiation of nociceptive input in the S1 cortex.

Synaptic Basis for Whisker Deprivation-Induced Synaptic Depression in Rat Somatosensory Cortex

Whisker deprivation weakens excitatory layer 4 (L4) inputs to L2/3 pyramidal cells in rat primary somatosensory (S1) cortex, which is likely to contribute to whisker map plasticity. This weakening has been proposed to represent long-term depression (LTD) induced by sensory deprivation in vivo. Here, we studied the synaptic expression mechanisms for deprivation-induced weakening of L4-L2/3 inputs and assessed its similarity to LTD, which is known to be expressed presynaptically at L4-L2/3 synapses. Whisker deprivation increased the paired pulse ratio at L4-L2/3 synapses and slowed the use-dependent block of NMDA receptor currents by MK-801 [(5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], indicating that deprivation reduced transmitter release probability at these synapses. In contrast, deprivation did not alter either miniature EPSC amplitude in L2/3 neurons or the amplitude of quantal L4-L2/3 synaptic responses measured in strontium, indicating that postsynaptic responsiveness was unchanged. In young postnatal day 12 (P12) rats, at least 4 d of deprivation were required to significantly weaken L4-L2/3 synapses. Similar weakening occurred when deprivation began at older ages (P20), when synapses are mostly mature, indicating that weakening is unlikely to represent a failure of synaptic maturation but instead represents a reduction in the strength of existing synapses. Thus, whisker deprivation weakens L4-L2/3 synapses by decreasing presynaptic function, similar to known LTD mechanisms at this synapse.

Organization of pontocerebellar projections to identified climbing fiber zones in the rat

The organization of pontocerebellar projections to the paravermis and hemisphere of the posterior cerebellum of the rat was studied in relation to the organization of climbing fibers. Small injections of cholera toxin subunit B were placed in the cerebellar cortex at locations predetermined by evoked climbing fiber potentials from selected body parts or based on coordinates. The injection site was characterized with respect to the zebrin pattern and by the distribution of retrogradely labeled neurons in the inferior olive. The following zones were studied: hindlimb-related zones C1 and C2 of lobule VIII; forelimb-related zones C1, C2, and D0/D1 of the paramedian lobule; and face-related zones A2 of the paramedian lobule and C2 and D0 of crus 2B. The results show that the distribution of pontine neurons is closely related to the climbing fiber somatotopy. Injections centered on face-related zones result in distribution of pontine neurons within the pontine core region. Forelimb regions surround this core, whereas hindlimb regions are mostly supplied by caudal pontine regions and by a single patch of more rostrally located neurons. This distribution fits well with published data on the somatotopy of the corticopontine projection from the rat primary somatosensory cortex. However, apart from differences in the participation of ipsilaterally projecting cells, the distribution of pontine neurons does not change significantly when the injection covers different zones of the same lobule such as C1 and C2 of lobule VIII; C1, C2, and D0/D1 of the paramedian lobule; A2 of the paramedian lobule; and C2 and D0 of crus 2B.

Current source density analysis of laser heat-evoked intra-cortical field potentials in the primary somatosensory cortex of rats

The role of the primary somatosensory cortex in thermal pain perception has been established. However, the cortical circuitry that mediates the thermo-nociceptive information processing has not been elucidated. The aim of present study was to investigate the intracortical synaptic currents in primary somatosensory cortex evoked by short laser pulses and to determine their transmission pathway. Noxious CO 2 laser pulse stimuli or innocuous electrical and mechanical stimuli were delivered to the hind paw of halothane-anesthetized rats. Multi-channel field potentials were recorded simultaneously in primary somatosensory cortex and laminar-specific transmembrane currents were analyzed using a current source density method. A distinct spatial–temporal pattern of intra-cortical sink source currents was evoked by laser pulse stimuli. The amplitude of the early component was graded by laser energy output and influenced by contralateral signals, whereas the late components were not intensity-dependent and exhibited bilateral excitation. Intra-cortical current flows revealed that synaptic activation occurred initially at layers IV and VI separately and then was relayed transynaptically to the more superficial and the deeper layers. Latency, amplitude and intracortical distributions of the activated intra-cortical currents evoked by noxious stimuli differed significantly from those evoked by innocuous stimuli. Conduction velocity data together with the results of tetrodotoxin, capsaicin and morphine treatments indicated that the early and late components were mediated separately by A-delta and C fibers. Our results suggest that large and small diameter thermal nociceptive afferents generated laminar-specific intracortical synaptic currents in primary somatosensory cortex and that these excitatory synaptic currents were conveyed separately by lateral and medial thalamic nuclei.

Endogenous fluorescence imaging of somatosensory cortical activities after discrimination learning in rats

Aerobic energy metabolism in the brain is reflected as changes in the green fluorescence of mitochondrial flavoproteins, and the activity-dependent changes in endogenous fluorescence are applicable for functional brain imaging. To understand the roles of cortical plasticity in discrimination learning, we used flavoprotein fluorescence imaging to visualize changes of neural activities in the rat primary somatosensory cortex (SI) after learning. Rats were trained to discriminate floor vibration at rewarded and unrewarded frequencies. After this discrimination learning was accomplished in 3–5 days, the rats were anesthetized with urethane (1.5 g/kg, i.p.), and neural responses were recorded in SI during flutter stimuli applied to the contralateral hindpaw. The fluorescence responses to the stimuli at unrewarded frequencies were selectively depressed in the trained rats, which had behaviorally neglected unrewarded stimuli. The depression of cortical responses was not observed in the rats trained with rewarded stimuli only. Therefore, the stimulus-specific depression in SI might explain a part of neural mechanisms underlying discrimination behavior. To reproduce the stimulus-specific depression of cortical responses in anesthetized rats, tetanic cortical stimulation was paired with flutter stimulation applied to the hindpaw. Selective depression of fluorescence responses or field potentials in SI was induced by the paired stimulation. Our findings suggest that some intracortical circuits in SI are specifically tuned to and modulated by unrewarded stimuli of a particular frequency while SI neurons are responsive to both of rewarded and unrewarded stimuli. The present results indicate the usefulness of flavoprotein fluorescence imaging for investigating somatosensory cortical plasticity after learning.

Structure of the Excitatory Receptive Fields of Infragranular Forelimb Neurons in the Rat Primary Somatosensory Cortex Responding To Touch

We quantitatively studied the excitatory receptive fields of 297 neurons recorded from the forelimb infragranular somatosensory cortex of the rat while touch stimuli were applied to discrete locations on the forelimbs. Receptive fields were highly heterogeneous, but they were regulated, on average, by an underlying spatio-temporal structure. We found the following. (i) Neurons responded with decreasing magnitude and increasing latency when the stimulus was moved from the primary location to secondary locations and to far ispilateral locations of their excitatory receptive fields, displaying smooth transitions from the primary location to secondary locations. (ii) Receptive field patterns revealed functional connectivity between the digits and ventral palm, which did not depend on whether the digits were stimulated dorsally or ventrally. (iii) The structure of the receptive fields (i.e. the neural responses to stimulation of secondary locations compared to the neural responses to stimulation of the primary location), reflected cortical (rather than body) distances. (iv) There was a functional separation between the forepaw and the rest of the forelimb. Namely: if the primary location was in the digits or palm, secondary locations were biased toward the digits and palm; if the primary location was in rest of the forelimb, secondary locations appeared equally distributed over forelimb, digits and palm. (v) More than 40% of neurons extended their receptive field to the ipsilateral forelimb, without any evident spatial organization. Overall, the stimuli evoked approximately 3 times more spikes from secondary responses than from primary responses. These results suggest that a rich repertoire of spatio-temporal responses is available for encoding tactile information. This highly distributed receptive field structure provides the electrophysiological architecture for studying organization and plasticity of cortical somatosensory processing.

Highlights from the Literature

Highlights from the Literature

Changes in Intrinsic Properties of Pyramidal Neurons in Adult Rat S1 During Cortical Reorganization

Peripheral denervation causes significant changes in the organization of developing or adult primary somatosensory cortex (S1). However, the basic mechanisms that underlie reorganization are not well understood. Most attention has been focused on possible synaptic mechanisms associated with reorganization. However, another important determinant of cortical circuit function is the intrinsic membrane properties of neurons in the circuit. Here we document changes in the intrinsic properties of pyramidal neurons in cortical layer 2/3 in adult rat primary somatosensory cortex (S1) after varying durations of forepaw denervation. Denervation of the forepaw induced a rapid and sustained shift in the location of the border between the forepaw and lower jaw representations of adult S1 (reorganization). Coronal slices from the reorganized region were maintained in vitro and the intrinsic properties of layer 2/3 pyramidal neurons of S1 were determined using whole cell recordings. In general, passive membrane properties were not affected by denervation; however, a variety of active properties were. The most robust changes were increases in the amplitudes of the fast and medium afterhyperpolarization (AHP) and an increase in the interval between action potentials (APs). Additional changes at some durations of denervation were observed for the AP threshold. These observations indicate that changes in intrinsic properties, mostly reflecting a decrease in overall excitation, may play a role in changes in cortical circuit properties during reorganization in adult S1, and suggest a possible role for AHPs in some of those changes.

Role of Spike Timing in the Forelimb Somatosensory Cortex of the Rat

The aim of this study was to test the hypothesis that the significance of spike timing in somatosensory processing is not a specific feature of the whisker cortex but a more general characteristic of the primary somatosensory cortex. We recorded ensembles of neurons using microwire arrays implanted in the deep layers of the forelimb region of the rat primary somatosensory cortex in response to step stimuli delivered to the cutaneous surface of the contralateral body. We used a recently developed peristimulus time histogram (PSTH)-based classification method to investigate the temporal precision of the code by evaluating how changing the bin size (from 40 to 1 msec) would affect the ability of the ensemble responses to discriminate stimulus location on a single-trial basis. The information related to the discrimination was redundantly distributed within the ensembles, and the ability to discriminate stimulus location increased when decreasing the bin size, reaching a maximum at 4 msec. In our experiment, at 4 msec bin size the first spike per neuron after the stimulus conveyed almost as much information as the entire responses, so the temporal precision of the code was preserved in the first spikes. Subsequent spikes were less frequent but conveyed more information per spike. Finally, not only the trials correctly classified but also the trials incorrectly classified conveyed information about stimulus location with a similar temporal precision. We conclude that the role of spike timing in cortical somatosensory processing is not an exclusive feature of the highly specialized rat trigeminal system, but a more general property of the rat primary somatosensory cortex.