Neuronal Encoding of Multisensory Motion Features in the Rat Associative Parietal Cortex.

Motion perception is facilitated by the interplay of various sensory channels. In rodents, the cortical areas involved in multisensory motion coding remain to be identified. Using voltage-sensitive-dye imaging, we revealed a visuo-tactile convergent region that anatomically corresponds to the associative parietal cortex (APC). Single unit responses to moving visual gratings or whiskers deflections revealed a specific coding of motion characteristics strikingly found in both sensory modalities. The heteromodality of this region was further supported by a large proportion of bimodal neurons and by a classification procedure revealing that APC carries information about motion features, sensory origin and multisensory direction-congruency. Altogether, the results point to a central role of APC in multisensory integration for motion perception.

Hypergravity within a critical period impacts on the maturation of somatosensory cortical maps and their potential for use-dependent plasticity in the adult.

We investigated experience-dependent plasticity of somatosensory maps in rat S1 cortex during early development. We analyzed both short- and long-term effects of exposure to 2G hypergravity (HG) during the first 3 postnatal weeks on forepaw representations. We also examined the potential of adult somatosensory maps for experience-dependent plasticity after early HG rearing. At postnatal day 22, HG was found to induce an enlargement of cortical zones driven by nail displacements and a contraction of skin sectors of the forepaw map. In these remaining zones serving the skin, neurons displayed expanded glabrous skin receptive fields (RFs). HG also induced a bias in the directional sensitivity of neuronal responses to nail displacement. HG-induced map changes were still found after 16 wk of housing in normogravity (NG). However, the glabrous skin RFs recorded in HG rats decreased to values similar to that of NG rats, as early as the end of the first week of housing in NG. Moreover, the expansion of the glabrous skin area and decrease in RF size normally induced in adults by an enriched environment (EE) did not occur in the HG rats, even after 16 wk of EE housing in NG. Our findings reveal that early postnatal experience critically and durably shapes S1 forepaw maps and limits their potential to be modified by novel experience in adulthood.

Unilateral vestibular neurectomy induces a remodeling of somatosensory cortical maps.

Unilateral Vestibular Neurectomy (UVN) induces a postural syndrome whose compensation over time is underpinned by multimodal sensory substitution processes. However, at a chronic stage of compensation, UVN rats exhibit an enduring postural asymmetry expressed by an increase in the body weight on the ipsilesional paws. Given the anatomo-functional links between the vestibular nuclei and the primary somatosensory cortex (S1), we explored the interplay of vestibular and somatosensory cortical inputs following acute and chronic UVN. We determined whether the enduring imbalance in tactilo-plantar inputs impacts response properties of S1 cortical neurons and organizational features of somatotopic maps. We performed electrophysiological mapping of the hindpaw cutaneous representations in S1, immediately and one month after UVN. In parallel, we assessed the posturo-locomotor imbalance during the compensation process. UVN immediately induces an expansion of the cortical neuron cutaneous receptive fields (RFs) leading to a partial dedifferentiation of somatotopic maps. This effect was demonstrated for the ventral skin surface representations and was greater on the contralesional hindpaw for which the neuronal threshold to skin pressure strongly decreased. The RF enlargement was amplified for the representation of the ipsilesional hindpaw in relation to persistent postural asymmetries, but was transitory for the contralesional one. Our study shows, for the first time, that vestibular inputs exert a modulatory influence on S1 neuron's cutaneous responses. The lesion-induced cortical malleability highlights the influence of vestibular inputs on tactile processing related to postural control.

Sensorimotor training promotes functional recovery and somatosensory cortical map reactivation following cervical spinal cord injury.

Sensorimotor activity has been shown to play a key role in functional recovery after partial spinal cord injury (SCI). Most studies in rodents have focused on the rehabilitation of hindlimb locomotor functions after thoracic or lumbar SCI, whereas forelimb motor and somatosensory abilities after cervical SCI remain largely uninvestigated, despite the high incidence of such injuries in humans. Moreover, little is known about the neurophysiological substrates of training-induced recovery in supraspinal structures. This study was aimed at evaluating the effects of a training procedure combining both motor and sensory stimulation on behavioral performance and somatosensory cortical map remodeling after cervical (C4-C5) spinal hemisection in rats. This SCI severely impaired both sensory and motor capacities in the ipsilateral limbs. Without training, post-lesion motor capacities gradually improved, whereas forepaw tactile abilities remained impaired. Consistently, no stimulus-evoked responses were recorded within the forepaw representational zone in the primary somatosensory (S1) cortex at 2 months after the SCI. However, our data reveal that with training started from the 7th day post-lesion, a nearly complete recovery (characterized by an early and rapid improvement of motor functions) was associated with a gradual compensation of tactile deficits. Furthermore, the recovery of tactile abilities was correlated with the areal extent of reactivation of S1 cortex forepaw representations. Rehabilitative training promoted post-lesion adaptive plasticity, probably by enhancing endogenous activity within spared spinal and supraspinal circuits and pathways sustaining sensory and motor functions. This study highlights the beneficial effect of sensorimotor training in motor improvement and its critical influence on tactile recovery after SCI.

Experience-dependent changes in spatiotemporal properties of cutaneous inputs remodel somatosensory cortical maps following skin flap rotation.

Contiguous skin surfaces that tend to be synchronously stimulated are represented in neighbouring sectors of primary somatosensory maps. Moreover, neuronal receptive fields (RFs) are reshaped through ongoing competitive/cooperative interactions that segregate/desegregate inputs converging onto cortical neuronal targets. The present study was designed to evaluate the influence of spatio-temporal constraints on somatotopic map organization. A vascularized and innervated pedicle flap of the ventrum skin bearing nipples was rotated by 180 degrees . Electrophysiological maps of ventrum skin were elaborated in the same rats at 24 h after surgery and 2 weeks after parturition. Neurones with split RFs resulting from the surgical separation of formerly adjoining skin surfaces were more numerous in non-nursing than nursing rats. RFs that included newly adjacent skin surfaces on both sides of the scar line emerged in nursing rats, suggesting that the spatial contiguity of formerly separated skin surfaces induced a fusion of their cortical representations through nursing-induced stimulation. In addition, nursing-dependent inputs were found to reincorporate the rotated skin flap representation in an updated topographical organization of the cortical map. A skin territory including recipient and translocated skin areas was costimulated for 7 h, using a brushing device. Neural responses evoked by a piezoelectric-induced skin indentation before and after skin brushing confirmed the emergence of RFs crossing the scar line and contraction of non-brushed components of split RFs. Our findings provide further evidence that the spatiotemporal structure of sensory inputs changing rapidly or evolving in a natural context is critical for experience-dependent reorganization of cortical map topography.

Imprinting of idiosyncratic experience in cortical sensory maps: neural substrates of representational remodeling and correlative perceptual changes.

Over the past 30 years, extensive research has been conducted in the field of cortical plasticity, under the impetus of seminal studies showing that the mature brain retains a capacity to reorganize the morphological and functional architecture of its neural circuits in order to adapt to environmental changes and mediate functional recovery following injury. Much effort has been focused on determining how idiosyncratic experience translates into molecular, structural and physiological changes in the sensory and motor representations embedded within cortical networks. The wealth of data generated by a broad spectrum of experimental manipulations has allowed unprecedented progress in our understanding of the physiological processes and neuroplasticity mechanisms underlying cortical representational remodeling. The objective of the present review is to put various facets of cortical map plasticity into perspective so as to examine possible links between changes occurring at multiple scales of the neural organization of the mature brain. The main focus is on neural substrates that mediate the instructive influence of experience and behavioral context on cortical reorganization, and perceptual correlates of representational remodeling.

Cortical Merging in S1 as a Substrate for Tactile Input Grouping.

Perception is a reconstruction process guided by rules based on knowledge about the world. Little is known about the neural implementation of the rules of object formation in the tactile sensory system. When two close tactile stimuli are delivered simultaneously on the skin, subjects feel a unique sensation, spatially centered between the two stimuli. Voltage-sensitive dye imaging (VSDi) and electrophysiological recordings [local field potentials (LFPs) and single units] were used to extract the cortical representation of two-point tactile stimuli in the primary somatosensory cortex of anesthetized Long-Evans rats. Although layer 4 LFP responses to brief costimulation of the distal region of two digits resembled the sum of individual responses, approximately one-third of single units demonstrated merging-compatible changes. In contrast to previous intrinsic optical imaging studies, VSD activations reflecting layer 2/3 activity were centered between the representations of the digits stimulated alone. This merging was found for every tested distance between the stimulated digits. We discuss this laminar difference as evidence that merging occurs through a buildup stream and depends on the superposition of inputs, which increases with successive stages of sensory processing. These findings show that layers 2/3 are involved in the grouping of sensory inputs. This process that could be inscribed in the cortical computing routine and network organization is likely to promote object formation and implement perception rules.

Nursing-induced somatosensory cortex plasticity: temporally decoupled changes in neuronal receptive field properties are accompanied by modifications in activity-dependent protein expression.

This study is an attempt to gain insight into the malleability of representational maps in the primary somatosensory cortex in relation to the expression of proteins involved in inhibitory and excitatory neurotransmitter systems that contribute to maintain these maps in a dynamic state. Malleability of somatosensory maps is characterized by changes in the sizes of neuron receptive fields (RFs) affecting the representational grain and in the locations and submodalities of these RFs modifying the map extent. The concomitance of these alterations remains so far hypothetical. We used nursing as an evolving source of ethologically significant cutaneous stimulation. This cyclic behavior is particularly suited to investigating the time course of experience-dependent cortical changes. Electrophysiological maps of the ventrum skin were recorded twice in the same lactating rats between nursing initiation and several weeks after nursing. We found that reduction in RF size occurred earlier than map expansion. As nursing time declined, the map expansion was maintained longer than the RF sharpening. Based on this difference in time course, we compared the expression patterns of several activity-dependent proteins in relation to the RF plasticity. Western blot analysis showed an increase in glutamic acid decarboxylase expression that was concomitant with RF contraction. In contrast, NR2A subunit of NMDA and alpha calcium/calmodulin kinase type II were upregulated at times when map expansion was observed. We propose that inhibitory and excitatory plasticity mechanisms operating with different time courses may contribute to the temporal dissociation of nursing-induced RF reshaping and map expansion.

A delivery device for presentation of tactile stimuli during functional magnetic resonance imaging.

We describe a novel stimulus delivery system designed to present tactile stimuli to a subject in the tunnel of a magnetic resonance imaging (MRI) system. Using energy from an air-driven piston to turn a wheel, the device advances a conveyor belt with a pre-determined sequence of stimuli that differ in their spatial features into the tunnel of the MRI. The positioning of one or several stimulus objects in a window near the subject's hand is controlled by a photoelectric device that detects periodic openings in the conveyor belt. Using this electric signal to position each presentation avoids cumulative positioning errors and provides a signal related to the progression of the experiment. We used a series of shapes that differed in their spatial features but the device could carry stimuli with a diversity of shapes and textures. This flexibility allows the experimenter to design a wide variety of psychophysical experiments in the haptic world and possibly to compare and contrast these stimuli with the cognitive treatment of similar stimuli delivered to the other senses. Appropriate experimental design allows separation of motor, sensory and memory storage phases of mental processes.

Acute granulocyte macrophage-colony stimulating factor treatment modulates neuroinflammatory processes and promotes tactile recovery after spinal cord injury.

Neuroinflammation is known to play a key role in the prognosis of functional recovery after spinal cord injury (SCI). The involvement of microglial and mast cells in early and late stages of inflammation has been receiving increasing attention. This study was aimed at determining the influence of a pro-inflammatory cytokine, the granulocyte macrophage-colony stimulating factor (GM-CSF), on microglia and mast cell activation, glial scar formation and functional recovery following SCI. Rats were randomly injected with saline or GM-CSF one hour after a C4-C5 medio-lateral hemisection. To assess functional impairment and recovery, the rats were subjected to sensorimotor tasks for one month. Then, responses evoked by forepaw stimulation in the primary somatosensory cortex were recorded. We also quantified the changes in GM-CSF, IL-1ß, IL-6 and BDNF levels, the gliosis and lesion volume as well as microglial and mast cell density, and mast cell surface. Our findings show that GM-CSF promotes cortical reactivation and recovery of tactile abilities, whereas it does not influence motor performances. A transient decrease in pro-inflammatory cytokines after GM-CSF treatment was also observed, whereas the endogenous GM-CSF level was unchanged. While the beneficial role of GM-CSF in reducing glial scar is confirmed, our findings reveal that neuroinflammatory events mediated by microglial and mast cells as well as the alteration of IL-1ß and IL-6 levels are paralleled with an improvement in tactile recovery. These mechanisms could limit the duration and intensity of homeostatic imbalance and promote the plasticity of spared tissues.

Perceptual context-dependent remodeling of the forepaw map in the SI cortex of rats trained on tactile discrimination.

We combined behavioral assessment of texture discrimination and electrophysiological mapping of concomitant reorganization in the forepaw representation within the SI cortex. Rats were housed in enriched (EE) or impoverished (IE) environments which have been shown to remodel the forepaw map and possibly alter discriminative abilities. In addition, animals were trained to discriminate homogeneous floorboards of invariant roughness from heterogeneous floorboards of gradually decreasing roughness contrasts during locomotion. As reported recently, differences in perceptual abilities were not related to housing conditions, but to a predilection for a floorboard type [Bourgeon S, Xerri C, Coq JO. Abilities in tactile discrimination of textures in adult rats exposed to enriched or impoverished environments. Behav Brain Res 2004;153:217-231]. Consistently, the present study shows that cortical map remodeling resulting from short-duration daily experience can prevail over changes induced by housing conditions. The relative area of glabrous skin representation was related to the discrimination performance and learning abilities in the rats (H) with a predilection for heterogeneous floorboards, i.e. in the animals performing discrimination in the most challenging perceptual context. By contrast, this cortical area was influenced by the duration of sensory experience in rats (h) with a predilection for homogeneous floorboards. Both EE condition and training to discrimination selectively decreased the sizes of the SI neurons' receptive fields (RFs) located on glabrous skin. Smaller RFs and larger cortical areas serving glabrous skin were correlated with better perceptual performances and learning abilities in the H rats only. The present study shows that representational reorganization related to tactile discrimination performances depends upon the perceptual context.

Abilities in tactile discrimination of textures in adult rats exposed to enriched or impoverished environments.

In previous studies, we have shown that housing in enriched environment for about 3 months after weaning improved the topographic organization and decreased the size of the receptive fields (RFs) located on the glabrous skin surfaces in the forepaw maps of the primary somatosensory cortex (SI) in rats [Exp. Brain Res. 121 (1998) 191]. In contrast, housing in impoverished environment induced a degradation of the SI forepaw representation, characterized by topographic disruptions, a reduction of the cutaneous forepaw area and an enlargement of the glabrous RFs [Exp. Brain Res. 129 (1999) 518]. Based on these two studies, we postulated that these representational alterations could underlie changes in haptic perception. Therefore, the present study was aimed at determining the influence of housing conditions on the rat's abilities in tactile texture discrimination. After a 2-month exposure to enriched or impoverished environments, rats were trained to perform a discrimination task during locomotion on floorboards of different roughness. At the end of every daily behavioral session, rats were replaced in their respective housing environment. Rats had to discriminate homogeneous (low roughness) from heterogeneous floorboards (combination of two different roughness levels). To determine the maximum performance in texture discrimination, the roughness contrast of the heterogeneous texture was gradually reduced, so that homogeneous and heterogeneous floorboards became harder to differentiate. We found that the enriched rats learned the first steps of the behavioral task faster than the impoverished rats, whereas both groups exhibited similar performances in texture discrimination. An individual "predilection" for either homogeneous or heterogeneous floorboards, presumably reflecting a behavioral strategy, seemed to account for the absence of differences in haptic discrimination between groups. The sensory experience depending on the rewarded texture discrimination task seems to have a greater influence on individual texture discrimination abilities than the sensorimotor experience related to housing conditions.

Early and moderate sensory stimulation exerts a protective effect on perilesion representations of somatosensory cortex after focal ischemic damage.

Previous studies have shown that intensive training within an early critical time window after focal cortical ischemia increases the area of damaged tissue and is detrimental to behavioral recovery. We postulated that moderate stimulation initiated soon after the lesion could have protective effects on peri-infarct cortical somatotopic representations. Therefore, we have assessed the effects of mild cutaneous stimulation delivered in an attention-demanding behavioral context on the functional organization of the perilesion somatosensory cortex using high-density electrophysiological mapping. We compared the effects of 6-day training initiated on the 3rd day postlesion (early training; ET) to those of same-duration training started on the 8th day (delayed training; DT). Our findings confirm previous work showing that the absence of training aggravates representational loss in the perilesion zone. In addition, ET was found to be sufficient to limit expansion of the ischemic lesion and reduce tissue loss, and substantially maintain the neuronal responsiveness to tactile stimulation, thereby preserving somatotopic map arrangement in the peri-infarct cortical territories. By contrast, DT did not prevent tissue loss and only partially reinstated lost representations in a use-dependent manner within the spared peri-infarct cortical area. This study differentiates the effects of early versus delayed training on perilesion tissue and cortical map reorganization, and underscores the neuroprotective influence of mild rehabilitative stimulation on neuronal response properties in the peri-infarct cortex during an early critical period.

Plasticity of cortical maps: multiple triggers for adaptive reorganization following brain damage and spinal cord injury.

Sensory and motor representations embedded in topographic cortical maps are use-dependent, dynamically maintained, and self-organizing functional mosaics that constitute idiosyncratic entities involved in perceptual and motor learning abilities. Studies of cortical map plasticity have substantiated the view that local reorganization of sensory and motor areas has great significance in recovery of function following brain damage or spinal cord injury. In addition, the transfer of function to distributed cortical areas and subcortical structures represents an adaptive strategy for functional compensation. There is a growing consensus that subject-environment interactions, by continuously refining the canvas of synaptic connectivity and reshaping the anatomical and functional architecture of neural circuits, promote adaptive behavior throughout life. Taking advantage of use-dependent neural plasticity, early initiated rehabilitative procedures improve the potential for recovery.

Sensorimotor experience influences recovery of forelimb abilities but not tissue loss after focal cortical compression in adult rats.

Sensorimotor activity has been shown to play a key role in functional outcome after extensive brain damage. This study was aimed at assessing the influence of sensorimotor experience through subject-environment interactions on the time course of both lesion and gliosis volumes as well as on the recovery of forelimb sensorimotor abilities following focal cortical injury. The lesion consisted of a cortical compression targeting the forepaw representational area within the primary somatosensory cortex of adult rats. After the cortical lesion, rats were randomly subjected to various postlesion conditions: unilateral C5-C6 dorsal root transection depriving the contralateral cortex from forepaw somatosensory inputs, standard housing or an enriched environment promoting sensorimotor experience and social interactions. Behavioral tests were used to assess forelimb placement during locomotion, forelimb-use asymmetry, and forepaw tactile sensitivity. For each group, the time course of tissue loss was described and the gliosis volume over the first postoperative month was evaluated using an unbiased stereological method. Consistent with previous studies, recovery of behavioral abilities was found to depend on post-injury experience. Indeed, increased sensorimotor activity initiated early in an enriched environment induced a rapid and more complete behavioral recovery compared with standard housing. In contrast, severe deprivation of peripheral sensory inputs led to a delayed and only partial sensorimotor recovery. The dorsal rhizotomy was found to increase the perilesional gliosis in comparison to standard or enriched environments. These findings provide further evidence that early sensory experience has a beneficial influence on the onset and time course of functional recovery after focal brain injury.

Differential tactile and motor recovery and cortical map alteration after C4-C5 spinal hemisection.

After incomplete spinal cord injury (SCI), the adult central nervous system is spontaneously capable of substantial reorganizations that can underlie functional recovery. Most studies have focused on intraspinal reorganizations after SCI and not on the correlative cortical remodeling. Yet, differential studies of neural correlates of the recovery of sensory and motor abilities may be conducted by segregating motor and somatosensory representations in distinct and topologically organized primary cortical areas. This study was aimed at evaluating the effects of a cervical (C4-C5) spinal cord hemisection on sensorimotor performances and electrophysiological maps in primary somatosensory (S1) and motor (M1) cortices in adult rats. After SCI, an enduring loss of the affected forepaw tactile sensitivity was paralleled by the abolishment of somatosensory evoked responses in the deprived forepaw area within the S1 cortex. In contrast, severe motor deficits in unilateral forelimb were partially restored over the first postoperative month, despite remnant deficits in distal movement. The overall M1 map size was drastically reduced in SCI rats relative to intact rats. In the remaining M1 map, the shoulder and elbow movements were over-represented, consistent with the behavioral recovery of proximal joint movements in almost all rats. By contrast, residual wrist representations were observed in M1 maps of half of the rats that did not systematically correlate with a behavioral recovery of these joint movements. This study highlights the differential potential of ascending and descending pathways to reorganize after SCI.

A new rating scale for open-field evaluation of behavioral recovery after cervical spinal cord injury in rats.

The Basso, Beattie, Bresnahan (BBB) locomotor rating scale has proven a reliable tool to evaluate impairments of hindlimb locomotor skills after thoracic spinal cord injury (SCI). With the increasing use of cervical SCI rat models, there is a critical need to develop scoring scales designed to more precisely examine alteration and recovery of forelimb functions. The main goal of the present study was to elaborate and evaluate a new rating scale for open-field testing of the fore- and hindlimb locomotor functions after cervical SCI. We also assessed the effectiveness of this rating scale for discriminating the functional consequences of dorsolateral (Hdl group), lateral (Hl group), or complete C4 unilateral hemisections (Hc group). Our findings show that the new rating scale can be considered as a sensitive and reliable descriptor of the postoperative time course of deficits affecting differentially the fore- and hindlimb sensorimotor functions following injuries of various severities. This new method provides reproducible data and can be used reliably by non-expert examiners. The proposed rating scale appears to be a useful tool for the assessment of various treatments designed to promote functional recovery after SCI. See online Supplementary Material (scoring spreadsheet and videotape recordings) at www.liebertonline.com.