Neurons In Somatosensory Cortex Research Articles

Rate and timing of cortical responses driven by separate sensory channels.

The sense of touch comprises multiple sensory channels that each conveys characteristic signals during interactions with objects. These neural signals must then be integrated in such a way that behaviorally relevant information about the objects is preserved. To understand the process of integration, we implement a simple computational model that describes how the responses of neurons in somatosensory cortex-recorded from awake, behaving monkeys-are shaped by the peripheral input, reconstructed using simulations of neuronal populations that reproduce natural spiking responses in the nerve with millisecond precision. First, we find that the strength of cortical responses is driven by one population of nerve fibers (rapidly adapting) whereas the timing of cortical responses is shaped by the other (Pacinian). Second, we show that input from these sensory channels is integrated in an optimal fashion that exploits the disparate response behaviors of different fiber types.

Origins of choice-related activity in mouse somatosensory cortex.

During perceptual decisions about faint or ambiguous sensory stimuli, even identical stimuli can produce different choices. Spike trains from sensory cortex neurons can predict trial-to-trial variability in choice. Choice-related spiking is widely studied to link cortical activity to perception, but its origins remain unclear. Using imaging and electrophysiology, we found that mouse primary somatosensory cortex neurons showed robust choice-related activity during a tactile detection task. Spike trains from primary mechanoreceptive neurons did not predict choices about identical stimuli. Spike trains from thalamic relay neurons showed highly transient, weak choice-related activity. Intracellular recordings in cortex revealed a prolonged choice-related depolarization in most neurons that was not accounted for by feedforward thalamic input. Top-down axons projecting from secondary to primary somatosensory cortex signaled choice. An intracellular measure of stimulus sensitivity determined which neurons converted choice-related depolarization into spiking. Our results reveal how choice-related spiking emerges across neural circuits and within single neurons.

Correlation of fingertip shear force direction with somatosensory cortical activity in monkey.

To examine the activity of somatosensory cortex (S1) neurons to self-generated shear forces on the index and thumb, two monkeys were trained to grasp a stationary metal tab with a key grip and exert forces without the fingers slipping in one of four orthogonal directions for 1 s. A majority (∼85%) of slowly adapting and rapidly adapting (RA) S1 neurons had activity modulated with shear force direction. The cells were recorded mainly in areas 1 and 2 of the S1, although some area 3b neurons also responded to shear direction or magnitude. The preferred shear vectors were distributed in every direction, with tuning arcs varying from 50° to 170°. Some RA neurons sensitive to dynamic shear force direction also responded to static shear force but within a narrower range, suggesting that the direction of the shear force may influence the adaptation rate. Other neurons were modulated with shear forces in diametrically opposite directions. The directional sensitivity of S1 cortical neurons is consistent with recordings from cutaneous afferents showing that shear direction, even without slip, is a powerful stimulus to S1 neurons.

Biological and bionic hands: natural neural coding and artificial perception.

The first decade and a half of the twenty-first century brought about two major innovations in neuroprosthetics: the development of anthropomorphic robotic limbs that replicate much of the function of a native human arm and the refinement of algorithms that decode intended movements from brain activity. However, skilled manipulation of objects requires somatosensory feedback, for which vision is a poor substitute. For upper-limb neuroprostheses to be clinically viable, they must therefore provide for the restoration of touch and proprioception. In this review, I discuss efforts to elicit meaningful tactile sensations through stimulation of neurons in somatosensory cortex. I focus on biomimetic approaches to sensory restoration, which leverage our current understanding about how information about grasped objects is encoded in the brain of intact individuals. I argue that not only can sensory neuroscience inform the development of sensory neuroprostheses, but also that the converse is true: stimulating the brain offers an exceptional opportunity to causally interrogate neural circuits and test hypotheses about natural neural coding.

Mutation of the Dyslexia-Associated Gene Dcdc2 Enhances Glutamatergic Synaptic Transmission Between Layer 4 Neurons in Mouse Neocortex.

Variants in DCDC2 have been associated with reading disability in humans, and targeted mutation of Dcdc2 in mice causes impairments in both learning and sensory processing. In this study, we sought to determine whether Dcdc2 mutation affects functional synaptic circuitry in neocortex. We found mutation in Dcdc2 resulted in elevated spontaneous and evoked glutamate release from neurons in somatosensory cortex. The probability of release was decreased to wild-type level by acute application of N-methyl-d-aspartate receptor (NMDAR) antagonists when postsynaptic NMDARs were blocked by intracellular MK-801, and could not be explained by elevated ambient glutamate, suggesting altered, nonpostsynaptic NMDAR activation in the mutants. In addition, we determined that the increased excitatory transmission was present at layer 4-layer 4 but not thalamocortical connections in Dcdc2 mutants, and larger evoked synaptic release appeared to enhance the NMDAR-mediated effect. These results demonstrate an NMDAR activation-gated, increased functional excitatory connectivity between layer 4 lateral connections in somatosensory neocortex of the mutants, providing support for potential changes in cortical connectivity and activation resulting from mutation of dyslexia candidate gene Dcdc2.

NEUROPHYSIOLOGICAL METHODS IN EARLY DIAGNOSIS OF MULTIPLE SCLEROSIS AND ACUTE DISSEMINATED ENCEPHALOMYELITIS IN CHILDREN

The purpose of the study was to evaluate somatosensory and motor pathways condition in the early stages of multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) in children. Methods. Twenty (20) healthy children and 29 patients with ADEM (n=14) and MS (n=15) were enrolled into the study. All patients were examined by neurologist. They also passed brain MRI and CSF analysis (oligoclonal bands test), transcranial magnetic stimulation (TMS) and somatosensory evoked potentials (SSEP) examination.Results. In children with MS we revealed significant asymmetry of the conduction along the motor pathways on the spinal level, delay of conduction along somatosensory pathways on the spinal level and low functional state of somatosensory cortex neurons. Conclusions. The revealed differences may be caused by more severe spinal lesion at early stages of MS than in ADEM. The predominant SSEP abnormalities compared with TMS alteration indicate the sensibility of somatosensory pathways and sensory system at early stage of MS. SSEP and TMS may be recommended as standard methods of differential diagnosis of ADEM and MS in children.

Pathway-specific reorganization of projection neurons in somatosensory cortex during learning.

In the mammalian brain, sensory cortices exhibit plasticity during task learning, but how this alters information transferred between connected cortical areas remains unknown. We found that divergent subpopulations of cortico-cortical neurons in mouse whisker primary somatosensory cortex (S1) undergo functional changes reflecting learned behavior. We chronically imaged activity of S1 neurons projecting to secondary somatosensory (S2) or primary motor (M1) cortex in mice learning a texture discrimination task. Mice adopted an active whisking strategy that enhanced texture-related whisker kinematics, correlating with task performance. M1-projecting neurons reliably encoded basic kinematics features, and an additional subset of touch-related neurons was recruited that persisted past training. The number of S2-projecting touch neurons remained constant, but improved their discrimination of trial types through reorganization while developing activity patterns capable of discriminating the animal's decision. We propose that learning-related changes in S1 enhance sensory representations in a pathway-specific manner, providing downstream areas with task-relevant information for behavior.

La(3+) Alters the Response Properties of Neurons in the Mouse Primary Somatosensory Cortex to Low-Temperature Noxious Stimulation of the Dental Pulp.

Although dental pain is a serious health issue with high incidence among the human population, its cellular and molecular mechanisms are still unclear. Transient receptor potential (TRP) channels are assumed to be involved in the generation of dental pain. However, most of the studies were conducted with molecular biological or histological methods. In vivo functional studies on the role of TRP channels in the mechanisms of dental pain are lacking. This study uses in vivo cellular electrophysiological and neuropharmacological method to directly disclose the effect of LaCl3, a broad spectrum TRP channel blocker, on the response properties of neurons in the mouse primary somatosensory cortex to low-temperature noxious stimulation of the dental pulp. It was found that LaCl3 suppresses the high-firing-rate responses of all nociceptive neurons to noxious low-temperature stimulation and also inhibits the spontaneous activities in some nonnociceptive neurons. The effect of LaCl3 is reversible. Furthermore, this effect is persistent and stable unless LaCl3 is washed out. Washout of LaCl3 quickly revitalized the responsiveness of neurons to low-temperature noxious stimulation. This study adds direct evidence for the hypothesis that TRP channels are involved in the generation of dental pain and sensation. Blockade of TRP channels may provide a novel therapeutic treatment for dental pain.

Compartmental organization of synaptic inputs to parvalbumin-expressing GABAergic neurons in mouse primary somatosensory cortex.

Parvalbumin (PV)-positive fast-spiking cells in the neocortex are known to generate gamma oscillations by mutual chemical and electrical connections. Recent findings suggest that this rhythm might be responsible for higher-order brain functions, and related to psychiatric disorders. To elucidate the precise structural rules of the connections of PV neurons, we first produced genetic tools. Using a lentiviral expression system, we developed neuron-specific promoters and a new reporter protein that labels the somatodendritic membrane of neurons. We applied the reporter protein to the generation of transgenic mice, and succeeded in visualizing the dendrites and cell bodies of PV neurons efficiently. Then we analyzed excitatory and inhibitory inputs to PV neurons in the primary somatosensory cortex using the mice. Corticocortical glutamatergic inputs were more frequently found on the distal dendrites than on the soma, whereas thalamocortical inputs did not differ between the proximal and distal portions. Corticocortical inhibitory inputs were more densely distributed on the soma than on the dendrites. We further investigated which types of neocortical GABAergic neurons preferred the PV soma over their dendrites. We revealed that the somatic and dendritic compartments principally received GABAergic inputs from vasoactive intestinal polypeptide (VIP)-positive and PV neurons, respectively. This compartmental organization suggests that PV neurons communicate with each other mainly via the dendrites, and that their activity is effectively controlled by the somatic inputs of VIP neurons. These findings provide new insights into the neuronal circuits involving PV neurons, and contribute to a better understanding of brain functions and mental disorders.

Temporal correlation mechanisms and their role in feature selection: a single-unit study in primate somatosensory cortex.

Author SummaryAttention can select stimuli in space based on the stimulus features most relevant for a task. Attention effects have been linked to several important phenomena such as modulations in neuronal spiking rate (i.e., the average number of spikes per unit time) and spike-spike synchrony between neurons. Attention has also been associated with spike count correlations, a measure that is thought to reflect correlated noise in the population of neurons. Here, we studied whether feature-based attention biases the correlated activity between neurons when attention is directed towards their common preferred feature. Simultaneous single-unit recordings were obtained from multiple neurons in secondary somatosensory cortex in non-human primates performing feature-attention tasks. Both firing rate and spike-synchrony were enhanced when attention was directed towards the preferred feature of cells. However, attention effects on spike-synchrony had a tighter relationship with behavior. Further, attention decreased spike-count correlations when it was directed towards the receptive field of cells. Our data indicate that temporal correlation codes play a role in mediating feature selection, and are consistent with a feature-based selection model that operates by reducing the overall noise in a population and synchronizing activity across subpopulations that encode the relevant features of sensory stimuli.

Temporal precision in population-but not individual neuron-dynamics reveals rapid experience-dependent plasticity in the rat barrel cortex.

Cortical reorganization following sensory deprivation is characterized by alterations in the connectivity between neurons encoding spared and deprived cortical inputs. The extent to which this alteration depends on Spike Timing Dependent Plasticity (STDP), however, is largely unknown. We quantified changes in the functional connectivity between layer V neurons in the vibrissal primary somatosensory cortex (vSI) (barrel cortex) of rats following sensory deprivation. One week after chronic implantation of a microelectrode array in vSI, sensory-evoked activity resulting from mechanical deflections of individual whiskers was recorded (control data) after which two whiskers on the contralateral side were paired by sparing them while trimming all other whiskers on the rat's mystacial pad. The rats' environment was then enriched by placing novel objects in the cages to encourage exploratory behavior with the spared whiskers. Sensory-evoked activity in response to individual stimulation of spared whiskers and adjacent re-grown whiskers was then recorded under anesthesia 1–2 days and 6–7 days post-trimming (plasticity data). We analyzed spike trains within 100 ms of stimulus onset and confirmed previously published reports documenting changes in receptive field sizes in the spared whisker barrels. We analyzed the same data using Dynamic Bayesian Networks (DBNs) to infer the functional connectivity between the recorded neurons. We found that DBNs inferred from population responses to stimulation of each of the spared whiskers exhibited graded increase in similarity that was proportional to the pairing duration. A significant early increase in network similarity in the spared-whisker barrels was detected 1–2 days post pairing, but not when single neuron responses were examined during the same period. These results suggest that rapid reorganization of cortical neurons following sensory deprivation may be mediated by an STDP mechanism.

Physiology and Impact of Horizontal Connections in Rat Neocortex.

Cortical information processing at the cellular level has predominantly been studied in local networks, which are dominated by strong vertical connectivity between layers. However, recent studies suggest that the bulk of axons targeting pyramidal neurons most likely originate from outside this local range, emphasizing the importance of horizontal connections. We mapped a subset of these connections to L5B pyramidal neurons in rat somatosensory cortex with photostimulation, identifying intact projections up to a lateral distance of 2 mm. Our estimates of the spatial distribution of cells presynaptic to L5B pyramids support the idea that the majority is located outside the local volume. The synaptic physiology of horizontal connections does not differ markedly from that of local connections, whereas the layer and cell-type-dependent pattern of innervation does. Apart from L2/3, L6A provides a strong source of horizontal connections. Implementing our data into a spiking neuronal network model shows that more horizontal connections promote robust asynchronous ongoing activity states and reduce noise correlations in stimulus-induced activity.

The neural basis of tactile motion perception.

The manipulation of objects commonly involves motion between object and skin. In this review, we discuss the neural basis of tactile motion perception and its similarities with its visual counterpart. First, much like in vision, the perception of tactile motion relies on the processing of spatiotemporal patterns of activation across populations of sensory receptors. Second, many neurons in primary somatosensory cortex are highly sensitive to motion direction, and the response properties of these neurons draw strong analogies to those of direction-selective neurons in visual cortex. Third, tactile speed may be encoded in the strength of the response of cutaneous mechanoreceptive afferents and of a subpopulation of speed-sensitive neurons in cortex. However, both afferent and cortical responses are strongly dependent on texture as well, so it is unclear how texture and speed signals are disambiguated. Fourth, motion signals from multiple fingers must often be integrated during the exploration of objects, but the way these signals are combined is complex and remains to be elucidated. Finally, visual and tactile motion perception interact powerfully, an integration process that is likely mediated by visual association cortex.

Convergence across tactile afferent types in primary and secondary somatosensory cortices.

Integration of information by convergence of inputs onto sensory cortical neurons is a requisite for processing higher-order stimulus features. Convergence across defined peripheral input classes has generally been thought to occur at levels beyond the primary sensory cortex, however recent work has shown that this does not hold for the convergence of slowly-adapting and rapidly-adapting inputs in primary somatosensory cortex. We have used a new analysis method for multi-unit recordings, to show convergence of inputs deriving from the rapidly-adapting and Pacinian channels in a proportion of neurons in both primary and secondary somatosensory cortex in the anaesthetised cat. We have validated this method using single-unit recordings. The secondary somatosensory cortex has a greater proportion of sites that show convergence of this type than primary somatosensory cortex. These findings support the hypothesis that the more complex features processed in higher cortical areas require a greater degree of convergence across input classes, but also shows that this convergence is apparent in the primary somatosensory cortex.

Potentiation of convergent synaptic inputs onto pyramidal neurons in somatosensory cortex: Dependence on brain wave frequencies and NMDA receptor subunit composition

N-methyl-d-aspartate receptors (NMDARs) at layer (L)1/primary whisker motor cortex synaptic inputs are distinct from thalamic/striatal (Str) synaptic inputs onto L5 pyramidal neurons in the rat somatosensory cortex. However, the consequences of differential expression of putative GluN3A-containing triheteromeric NMDARs at L1 inputs and GluN2A-containing diheteromeric NMDARs at Str inputs on plasticity of the underlying synapses at the respective inputs remain unknown. Here we demonstrate that L1, but not Str, synapses are potentiated following delta burst stimulation (dBS). This potentiation is blocked by d-serine and/or intracellular 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) suggesting that it is subunit-specific and dependent on elevations in intracellular Ca2+. Interestingly, ifenprodil, the GluN2B-preferring antagonist, suppresses baseline L1 responses but does not prevent induction of dBS-evoked potentiation. Unlike L1, Str synapses are maximally potentiated following theta burst stimulation (tBS) and this potentiation is blocked with BAPTA and/or the GluN2A-preferring antagonist NVP-AAM077. We show further that while dBS is both necessary and sufficient to potentiate L1 synapses, tBS is most effective in potentiating Str synapses. Our data suggest distinct potentiating paradigms for the two convergent inputs onto pyramidal neurons in the somatosensory cortex and co-dependence of synaptic potentiation on brain wave-tuned frequencies of burst stimulation and subunit composition of underlying NMDARs. A model for predicting the likelihood of enhancing synaptic efficacy is proposed based on Ca2+ influx through these receptors and integration of EPSPs at these inputs. Together, these findings raise the possibility of input-specific enhancements of synaptic efficacy in neurons as a function of the animal’s behavioral state and/or arousal in vivo.

Intrinsic properties of and thalamocortical inputs onto identified corticothalamic-VPM neurons

Corticothalamic (CT) feedback plays an important role in regulating the sensory information that the cortex receives. Within the somatosensory cortex layer VI originates the feedback to the ventral posterior medial (VPM) nucleus of the thalamus, which in turn receives sensory information from the contralateral whiskers. We examined the physiology and morphology of CT neurons in rat somatosensory cortex, focusing on the physiological characteristics of the monosynaptic inputs that they receive from the thalamus. To identify CT neurons, rhodamine microspheres were injected into VPM and allowed to retrogradely transport to the soma of CT neurons. Thalamocortical slices were prepared at least 3 days post injection. Whole-cell recordings from labeled CT cells in layer VI demonstrated that they are regular spiking neurons and exhibit little spike frequency adaption. Two anatomical classes were identified based on their apical dendrites that either terminated by layer V (compact cells) or layer IV (elaborate cells). Thalamic inputs onto identified CT-VPM neurons demonstrated paired pulse depression over a wide frequency range (2–20 Hz). Stimulus trains also resulted in significant synaptic depression above 10 Hz. Our results suggest that thalamic inputs differentially impact CT-VPM neurons in layer VI. This characteristic may allow them to differentiate a wide range of stimulation frequencies which in turn further tune the feedback signals to the thalamus.

Steady-state dynamics and experience-dependent plasticity of dendritic spines of layer 4/5a pyramidal neurons in somatosensory cortex

Steady-state dynamics and experience-dependent plasticity of dendritic spines of layer 4/5a pyramidal neurons in somatosensory cortex

BDNF-endocannabinoid interactions at neocortical inhibitory synapses require phospholipase C signaling

Endogenous cannabinoids (endocannabinoids) and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), are potent synaptic modulators that are expressed throughout the forebrain and play critical roles in many behavioral processes. Although the effects of BDNF at excitatory synapses have been well characterized, the mechanisms of action of BDNF at inhibitory synapses are not well understood. Previously we have found that BDNF suppresses presynaptic GABA release in layer 2/3 of the neocortex via postsynaptic tropomyosin-related kinase receptor B (trkB) receptor-induced release of endocannabinoids. To examine the intracellular signaling pathways that underlie this effect, we used pharmacological approaches and whole cell patch-clamp techniques in layer 2/3 pyramidal neurons of somatosensory cortex in brain slices from juvenile Swiss CD1 mice. Our results indicated that phospholipase Cγ (PLCγ) is involved in the CB1 receptor-mediated synaptic effect of BDNF, because the BDNF effect was blocked in the presence of the broad-spectrum PLC inhibitors U-73122 and edelfosine, whereas the inactive analog U-73343 did not alter the suppressive effect of BDNF at inhibitory synapses. Endocannabinoid release can also be triggered by metabotropic glutamate receptor (mGluR)-mediated activation of PLCβ, and BDNF has been shown to enhance spontaneous glutamate release. An mGluR antagonist, E4CPG, however, did not block the BDNF effect. In addition, the effect of BDNF was independent of other signaling pathways downstream of trkB receptor activation, namely, mitogen-activated protein kinase and phosphoinositide 3-kinase pathways, as well as protein kinase C signaling.

Rapid adult experience-dependent anatomical plasticity in layer IV of primary somatosensory cortex

Sensory deprivation, such as whisker deprivation, is one of the most common paradigms used to examine experience-dependent plasticity. Many of these studies conducted during development have demonstrated anatomical and synaptic neocortical plasticity with varying lengths of deprivation (for review, see Holtmaat and Svoboda, 2009). However, to date, there have been few studies exploring brief periods of experience-dependent neocortical plasticity in adulthood, similar to that observed from learning and memory paradigms (Siucinska and Kossut, 1996, 2004; Galvez et al., 2006; Chau et al., 2013). Examining both synapsin I and Golgi-Cox stained neurons in primary somatosensory cortex of unilaterally whisker-deprived adult mice, the current study demonstrates that 5 days of whisker deprivation results in more synapses in spared barrels and reduced synapses in deprived barrels. To our knowledge, this is the first study to characterize anatomical changes in layer IV of primary somatosensory cortex after a brief period of sensory deprivation in adulthood. Furthermore, findings from the present study suggest that analyses from prolonged periods of either sensory deprivation or stimulation during adulthood are missing forms of plasticity that could provide better insight into various cognitive processes, such as learning and memory.

Modulation of high- and low-frequency components of the cortical local field potential via nicotinic and muscarinic acetylcholine receptors in anesthetized mice

Release of acetylcholine (ACh) in neocortex is important for learning, memory and attention tasks. The primary source of ACh in neocortex is axons ascending from the basal forebrain. Release of ACh from these axons evokes changes in the cortical local field potential (LFP), including a decline in low-frequency spectral power that is often referred to as desynchronization of the LFP and is thought to result from the activation of muscarinic ACh receptors. Using channelrhodopsin-2, we selectively stimulated the axons of only cholinergic basal forebrain neurons in primary somatosensory cortex of the urethane-anesthetized mouse while monitoring the LFP. Cholinergic stimulation caused desynchronization and two brief increases in higher-frequency power at stimulus onset and offset. Desynchronization (1-6 Hz) was localized, extending ≤ 1 mm from the edge of stimulation, and consisted of both nicotinic and muscarinic receptor-mediated components that were inhibited by mecamylamine and atropine, respectively. Hence we have identified a nicotinic receptor-mediated component to desynchronization. The increase in higher-frequency power (>10 Hz) at stimulus onset was also mediated by activation of nicotinic and muscarinic receptors. However, the increase in higher-frequency power (10-20 Hz) at stimulus offset was evoked by activation of muscarinic receptors and inhibited by activation of nicotinic receptors. We conclude that the activation of nicotinic and muscarinic ACh receptors in neocortex exerts several effects that are reflected in distinct frequency bands of the cortical LFP in urethane-anesthetized mice.