Synaptic basis for developmental plasticity in somatosensory cortex

Sensory experience drives plasticity of the body map in developing and adult somatosensory cortex, but the synaptic mechanisms underlying such plasticity are not well understood. Recently, several mechanisms that are likely to contribute to map plasticity have been directly observed in response to altered experience in vivo. These mechanisms include long-term potentiation and long-term depression at specific excitatory synapses, competition between lemniscal (barrel) and non-lemniscal (septal) processing streams, and regulation of the number of inhibitory synapses.     

Experience-induced plasticity of cutaneous maps in the primary somatosensory cortex of adult monkeys and rats

In a first study, the representations of skin surfaces of the hand in the primary somatosensory cortex, area 3b, were reconstructed in owl monkeys and squirrel monkeys trained to pick up food pellets from small, shallow wells, a task which required skilled use of the digits. Training sessions included limited manual exercise over a total period of a few hours of practice. From an early clumsy performance in which many retrieval attempts were required for each successful pellet retrieval, the monkeys exhibited a gradual improvement. Typically, the animals used various combinations of digits before developing a successful retrieval strategy. As the behavior came to be stereotyped, monkeys consistently engaged surfaces of the distal phalanges of one or two digits in the palpation and capture of food pellets from the smallest wells. Microelectrode mapping of the hand surfaces revealed that the glabrous skin of the fingertips predominantly involved in the dexterity task was represented over topographically expanded cortical sectors. Furthermore, cutaneous receptive fields which covered the most frequently stimulated digital tip surfaces were less than half as large as were those representing the corresponding surfaces of control digits. In a second series of experiments, Long-Evans rats were assigned to environments promoting differential tactile experience (standard, enriched, and impoverished) for 80 to 115 days from the time of weaning. A fourth group of young adult rat experienced a severe restriction of forepaw exploratory movement for either 7 or 15 days. Cortical maps derived in the primary somatosensory cortex showed that environmental enrichment induced a substantial enlargement of the cutaneous forepaw representation, and improved its spatial resolution (smaller glabrous receptive fields). In contrast, tactile impoverishment resulted in a degradation of the forepaw representation that was characterized by larger cutaneous receptive fields and the emergence of non-cutaneous responses. Cortical maps derived in the hemispheres contralateral to the immobilized forelimb exhibited a severe decrease of about 50% in the overall areal extent of the cutaneous representation of the forepaw, which resulted from the invasion of topographically organized cortical zones of non-cutaneous responses, and numerous discontinuities in the representation of contiguous skin territories. The size and the spatial arrangement of the cutaneous receptive fields were not significantly modified by the immobilization of the contralateral forelimb. Similar results were obtained regardless of whether the forelimb restriction lasted 7 or 15 days. These two studies corroborate the view that representational constructs are permanently reshaped by novel experiences through dynamic competitive processes. These studies also support the notion that subject-environment interactions play a crucial role in the maintenance of basic organizational features of somatosensory representations.     

Experience-dependent plasticity mechanisms for neural rehabilitation in somatosensory cortex

Functional rehabilitation of the cortex following peripheral or central nervous system damage is likely to be improved by a combination of behavioural training and natural or therapeutically enhanced synaptic plasticity mechanisms. Experience-dependent plasticity studies in the somatosensory cortex have begun to reveal those synaptic plasticity mechanisms that are driven by sensory experience and might therefore be active during behavioural training. In this review the anatomical pathways, synaptic plasticity mechanisms and structural plasticity substrates involved in cortical plasticity are explored, focusing on work in the somatosensory cortex and the barrel cortex in particular.     

Tactile stimulation-induced rapid elevation of the synaptophysin mRNA expression level in rat somatosensory cortex

Synaptophysin is an integral membrane protein abundant in the synaptic vesicle and is found in nerve terminals throughout the brain. It was recently suggested that synaptophysin is also involved in the modulation of activity-dependent synapse formation. In this study, we examined at the individual level whether tactile stimulation selectively influenced the synaptophysin mRNA expression level in the somatosensory cortex of rats. Anesthetized rats were caressed on the back by an experimenter's palms for 20 min and the mRNA expression levels in the somatosensory and the visual cortices 5 min afterwards were determined using quantitative PCR methodology. The synaptophysin mRNA expression level was selectively higher in the experimental group than in the control group in the somatosensory cortex but not in the visual cortex. This suggests that the mRNA expression level of synaptophysin induced by neuronal activity is related to the regulation of synapse formation or remodeling or both.     

Gamma oscillations in human primary somatosensory cortex reflect pain perception

Successful behavior requires selection and preferred processing of relevant sensory information. The cortical representation of relevant sensory information has been related to neuronal oscillations in the gamma frequency band. Pain is of invariably high behavioral relevance and, thus, nociceptive stimuli receive preferred processing. Here, by using magnetoencephalography, we show that selective nociceptive stimuli induce gamma oscillations between 60 and 95 Hz in primary somatosensory cortex. Amplitudes of pain-induced gamma oscillations vary with objective stimulus intensity and subjective pain intensity. However, around pain threshold, perceived stimuli yielded stronger gamma oscillations than unperceived stimuli of equal stimulus intensity. These results show that pain induces gamma oscillations in primary somatosensory cortex that are particularly related to the subjective perception of pain. Our findings support the hypothesis that gamma oscillations are related to the internal representation of behaviorally relevant stimuli that should receive preferred processing.     

Millisecond-timescale local network coding in the rat primary somatosensory cortex

Correlation among neocortical neurons is thought to play an indispensable role in mediating sensory processing of external stimuli. The role of temporal precision in this correlation has been hypothesized to enhance information flow along sensory pathways. Its role in mediating the integration of information at the output of these pathways, however, remains poorly understood. Here, we examined spike timing correlation between simultaneously recorded layer V neurons within and across columns of the primary somatosensory cortex of anesthetized rats during unilateral whisker stimulation. We used bayesian statistics and information theory to quantify the causal influence between the recorded cells with millisecond precision. For each stimulated whisker, we inferred stable, whisker-specific, dynamic bayesian networks over many repeated trials, with network similarity of 83.3±6% within whisker, compared to only 50.3±18% across whiskers. These networks further provided information about whisker identity that was approximately 6 times higher than what was provided by the latency to first spike and 13 times higher than what was provided by the spike count of individual neurons examined separately. Furthermore, prediction of individual neurons' precise firing conditioned on knowledge of putative pre-synaptic cell firing was 3 times higher than predictions conditioned on stimulus onset alone. Taken together, these results suggest the presence of a temporally precise network coding mechanism that integrates information across neighboring columns within layer V about vibrissa position and whisking kinetics to mediate whisker movement by motor areas innervated by layer V.     

Age-dependent changes of short-latency somatosensory evoked potentials in healthy adults

Age-dependent changes of short-latency somatosensory evoked potentials following median nerve stimulation in humans were investigated in two groups of healthy adults aged 20-30 and 50-60 years. Normative values for both age groups are given. Compared to the younger group, in the older one P27 latency and N20-P27 interpeak latency were about 2 ms longer, and P27-N35 and P27-P45 interpeak latencies were significantly decreased. These findings suggest that N20 and P27 are generated by different structures and that the subsequent components do not depend on P27.     

Development and plasticity of the primary visual cortex

Hubel and Wiesel began the modern study of development and plasticity of primary visual cortex (V1), discovering response properties of cortical neurons that distinguished them from their inputs and that were arranged in a functional architecture. Their findings revealed an early innate period of development and a later critical period of dramatic experience-dependent plasticity. Recent studies have used rodents to benefit from biochemistry and genetics. The roles of spontaneous neural activity and molecular signaling in innate, experience-independent development have been clarified, as have the later roles of visual experience. Plasticity produced by monocular visual deprivation (MD) has been dissected into stages governed by distinct signaling mechanisms, some of whose molecular players are known. Many crucial questions remain, but new tools for perturbing cortical cells and measuring plasticity at the level of changes in connections among identified neurons now exist. The future for the study of V1 to illuminate cortical development and plasticity is bright.     

Optical imaging of nociception in primary somatosensory cortex of non-human primates

While the activation of primary somatosensory (SI) cortex during pain perception is consistently reported in functional imaging studies on normal subjects and chronic pain patients, the specific roles of SI, particularly the subregions within SI, in the processing of sensory aspects of pain are still largely unknown. Using optical imaging of intrinsic signal (OIS) and single unit electrophysiology, we studied cortical activation patterns within SI cortex (among Brodmann areas 3a, 3b and 1) and signal amplitude changes to various intensities of non-nociceptive, thermal nociceptive and mechanical nociceptive stimulation of individual distal finerpads in anesthetized squirrel monkeys. We have demonstrated that areas 3a and 1 are preferentially involved in the processing of nociceptive information while areas 3b and 1 are preferentially activated in the processing of non-nociceptive (touch) information. Nociceptive activations of individual fingerpad were organized topographically suggesting that nociceptive topographic map exits in areas 3a and 1. Signal amplitude was enhanced to increasing intensity of mechanical nociceptive stimuli in areas 3a, 3b and 1. Within area 1, nociceptive response co-localizes with the non-nociceptive response. Therefore, we hypothesize that nocicepitve information is area-specifically represented within SI cortex, in which nociceptive inputs are preferentially represented in areas 3a and 1 while non-nociceptive inputs are preferentially represented in areas 3b and 1.     

Ultrastructural changes in somatosensory cortex of albino rats during space flight

For the first time, mammalian brain has been studied during space flight aboard NASA orbital laboratory Spacelab-2. The main ultrastructural differences in the somatosensory cortex of the brain fixed under microgravity conditions and after landing include an increased number of degenerating presynaptic axon terminals after landing. Apparently, this is due to a sharp increase in afferent impulsation in the cortex during and after landing.     

Functional imaging of perceptual learning in human primary and secondary somatosensory cortex

Cellular mechanisms underlying synaptic plasticity are in line with the Hebbian concept. In contrast, data linking Hebbian learning to altered perception are rare. Combining functional magnetic resonance imaging with psychophysical tests, we studied cortical reorganization in primary and secondary somatosensory cortex (SI and SII) and the resulting changes of tactile perception before and after tactile coactivation, a simple type of Hebbian learning. Coactivation on the right index finger (IF) for 3 hr lowered its spatial discrimination threshold. In parallel, blood-oxygen level-dependent (BOLD) signals from the right IF representation in SI and SII enlarged. The individual threshold reduction was linearly correlated with the enlargement in SI, implying a close relation between altered discrimination and cortical reorganization. Controls consisting of a single-site stimulation did not affect thresholds and cortical maps. Accordingly, changes within distributed cortical networks based on Hebbian mechanisms alter the individual percept.     

An approach to localizing corneal pain representation in human primary somatosensory cortex

The cornea has been a focus of animal electrophysiological research for decades, but little is known regarding its cortical representation in the human brain. This study attempts to localize the somatotopic representation of the cornea to painful stimuli in human primary somatosensory cortex using functional magnetic resonance imaging (fMRI). In this case study, a subject was imaged at 3T while bright light was presented in a block-design, which either produced pain and blinking (during photophobia) or blinking alone (after recovery from photophobia). Pain and blinking produced precisely localized activations in primary somatosensory cortex and primary motor cortex. These results indicate that noxious stimulation of the cornea can produce somatotopic activation in primary somatosensory cortex. This finding opens future avenues of research to evaluate the relationship between corneal pain and central brain mechanisms relating to the development of chronic pain conditions, such as dry eye-like symptoms.     

Predicting spike occurrence and neuronal responsiveness from LFPs in primary somatosensory cortex

Local Field Potentials (LFPs) integrate multiple neuronal events like synaptic inputs and intracellular potentials. LFP spatiotemporal features are particularly relevant in view of their applications both in research (e.g. for understanding brain rhythms, inter-areal neural communication and neuronal coding) and in the clinics (e.g. for improving invasive Brain-Machine Interface devices). However the relation between LFPs and spikes is complex and not fully understood. As spikes represent the fundamental currency of neuronal communication this gap in knowledge strongly limits our comprehension of neuronal phenomena underlying LFPs. We investigated the LFP-spike relation during tactile stimulation in primary somatosensory (S-I) cortex in the rat. First we quantified how reliably LFPs and spikes code for a stimulus occurrence. Then we used the information obtained from our analyses to design a predictive model for spike occurrence based on LFP inputs. The model was endowed with a flexible meta-structure whose exact form, both in parameters and structure, was estimated by using a multi-objective optimization strategy. Our method provided a set of nonlinear simple equations that maximized the match between models and true neurons in terms of spike timings and Peri Stimulus Time Histograms. We found that both LFPs and spikes can code for stimulus occurrence with millisecond precision, showing, however, high variability. Spike patterns were predicted significantly above chance for 75% of the neurons analysed. Crucially, the level of prediction accuracy depended on the reliability in coding for the stimulus occurrence. The best predictions were obtained when both spikes and LFPs were highly responsive to the stimuli. Spike reliability is known to depend on neuron intrinsic properties (i.e. on channel noise) and on spontaneous local network fluctuations. Our results suggest that the latter, measured through the LFP response variability, play a dominant role.     

Dynamics of changes in somatosensory input to the motor cortex following lesion of somatosensory cortical areas in dogs

The pattern of change produced in somatosensory evoked potential (EP) in the forelimb projection area within the motor cortex (MI) following lesion of the projection area of the same limb in the somatosensory cortex (SI) or in parietal cortex area 5 was investigated during chronic experiments on waking dogs. Amplitude of the initial positive — negative wave of EP declined to 28–63% of preoperational level in all cases. No significant recovery of EP was noted for three weeks. Thus, a correlation between change in EP and spontaneous recuperation of the precision motor response occurring within two weeks after lesion of the SI did not exist. Nor was EP reinstated in the MI after ablation of area 5, despite complete but gradual reinstatement of EP (after an initial decline to 53%) in the nearby SI region. This protracted depression of EP seems to have been associated with breakdown of somatotopic sensory input from the SI or from area 5 to the MI, since EP in the motor cortex of the intact hemisphere and the hindlimb projection area within the MI on the lesioned side either remained unchanged or recovered within a week or two.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 1, pp. 61–68, January–February, 1990.     

Median and tibial nerve somatosensory evoked potentials: middle-latency components from the vicinity of the secondary somatosensory cortex in humans

The topography of the middle-latency N110 after radial nerve stimulation suggested a generator in SII. To support this hypothesis, we have tried to identify a homologous component in the tibial nerve SEP (somatosensory evoked potential). Evoked potentials following tibial nerve stimulation (motor+sensory threshold) were recorded with 29 electrodes (bandpass 0.5–500 Hz, sampling rate 1000 Hz). For comparison, the median nerve was stimulated at the wrist. Components were identified as peaks in the global field power (GFP). Map series were generated around GFP peaks and amplitudes were measured from electrodes near map maxima. With median nerve stimulation, we recorded a negativity with a maximum in temporal electrode positions and 106±12 ms peak latency (mean±SD), comparable to the N110 following radial nerve stimulation. After tibial nerve stimulation the latency of a component with the same topography was 131±11 ms (N130). Both N110 and N130 were present ipsi- as well as contralaterally. Amplitudes were significantly higher on the contralateral than the ipsilateral scalp for both median (3.1±2.4 μV vs. 1.7±1.6 μV) and tibial nerve (1.9±1.2 μV vs. 0.6+1 μV). The topography of the N130 can be explained by a generator in the vicinity of SII. The latency difference between median and tibial nerve stimulation is related to the longer conduction distance (cf. N20 and P40). The smaller ipsilateral N130 is consistent with the bilateral body representation in SII.     

Population coding in somatosensory cortex

Computational analyses have begun to elucidate which components of somatosensory cortical population activity may encode basic stimulus features. Recent results from rat barrel cortex suggest that the essence of this code is not synergistic spike patterns, but rather the precise timing of single neuron's first post-stimulus spikes. This may form the basis for a fast, robust population code.