Jacques-Olivier Coq

Environmental enrichment alters organizational features of the forepaw representation in the primary somatosensory cortex of adult rats

Abstract The cortical forepaw area of young adult rats was mapped by recording the response properties of small clusters of neurons in layer IV of the primary somatosensory (SI) cortex. First we quantitatively analyzed the somatotopic organizational features of the cortical forepaw representation in terms of areal extent and topography, receptive field (RF) sensory modality, size, and location. We also assessed the influence of environmental enrichment, known to induce structural alterations in cortical connectivity, on the representational characteristics of the forepaw maps. Long-Evans rats were housed in environments (standard, SE; enriched, EE) promoting differential tactile experience for 71–113 days from weaning. Within the SI, we found a single and complete topographic map of the cutaneous surfaces of the forepaw consisting of a rostrolateral-caudomedial sequence of digit and pad representational zones. Small islets of noncutaneous responses (NCR; high-threshold, deep-receptor input) within the boundaries of the cutaneous maps were a conspicuous feature of the forepaw map for SE rats. These islets created discontinuities in the representation of contiguous skin territories. In the SE rats, about 79% of the cortical sites activated by light tactile stimulation had a single cutaneous RF, whereas about 21% exhibited multiple RFs. Most single-digit RFs we delineated in the SE rats extended across two or three phalanges. As a result, the representations of the phalangeal skin surfaces were not segregated but formed an overlapping continuum. Moreover, within these regions, as the electrode was displaced in regular steps across the mediolateral axis, RFs did not shift across the digit skin surface in an orderly manner, suggesting a lack of internal topography in the finger representation zones. Tactile experience promoted by environmental enrichment induced alterations in the representational features of the SI cutaneous map of the forepaw. In EE rats, the areal extent of the forepaw cutaneous representation was 1.5 times larger than in SE rats. Indeed, the cutaneous map extended into NCR cortical sectors along its external margins and also into NCR islets found in the forepaw area. Consequently, in EE rats there were fewer representational discontinuities. The areal enlargement was due to a selective increase in the areal extent of the glabrous but not the hairy skin surface representations. Furthermore, protuberant glabrous skin (digit tips, palmar pads) was represented over larger cortical regions than were other glabrous skin territories less likely to be stimulated during object palpation and manipulation. Maps from EE rats were also characterized by a larger proportion of sites with single RFs (88% compared with 79%). In addition, glabrous RFs from EE rats were smaller and more clustered on the digit tips and palmar pads than were RFs in SE rat maps. RF size on hairy skin surfaces remained unchanged. Because the RFs were smaller, the cutaneous maps of EE rats contained distinct representations of digit phalangeal glabrous skin. RFs tended to exhibit more orderliness in their progression across the digit glabrous skin of EE rats than they did in SE rats. The phalanges of EE rats were represented in distinct patches. Neurons in EE rats were more sensitive to light tactile stimulation than were neurons in SE rats. These alterations were presumably mediated by the selective potentiation of cutaneous over deep-receptor activation. More generally, the present study corroborates the view that cortical cutaneous maps are maintained in a permanent state of use-dependent fluctuation.

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.

Tactile impoverishment and sensorimotor restriction deteriorate the forepaw cutaneous map in the primary somatosensory cortex of adult rats

Abstract We investigated the effects of sensory deprivation on the forepaw representation in the primary somatosensory cortex (SI) in the adult rat. Cortical maps were constructed from high-resolution multiunit recordings of the response of layer IV neurons to somatosensory stimuli. The main features of the forepaw representation were described in terms of areal extent and topography of the cortical map, and sensory submodality, size, and location of the receptive field (RF) of small clusters of the cortical neurons. After being weaned, two groups of Long-Evans rats were housed in a standard (SE) or impoverished (IE) environment for 65–115 days. A third group of SE rats was subjected to severe sensorimotor restriction (SR) of one forepaw for 7 days or 14 days, by using a one-sleeved cast. A concomitant effect of unilateral forelimb immobilization was a forced use of the nonrestricted forelimb in postural balance. The maps of both forepaws were derived 24 h after the cast was removed and the animal was allowed normal limb use. In a fourth group, SE rats experienced a 7-day immobilization followed by symmetrical limb use for 7 days before we mapped the hemisphere contralateral to the casted limb. For the SE and IE rats, the total areal extent of the cutaneous forepaw representation was similar, but IE rats exhibited a significant expansion of cortical islets serving high-threshold, presumably noncutaneous inputs, which were included in the cutaneous maps. In addition, SI neurons of IE rats had greatly enlarged glabrous, but not hairy, skin RFs. For the SR rats, the areal extent of the cutaneous map of the casted forepaw decreased by about 50%, after both 7- and 14-day forelimb immobilization. Large cortical sectors presumed to be formerly activated by cutaneous inputs were driven by high-threshold inputs that disrupted the somatotopic representation of the forepaw skin surfaces. These ”emergent” representational sectors were topographically organized. By contrast, the areal extent and topography of the noncasted forepaw representation did not differ from those of SE rats. The size of glabrous RFs on the casted forepaw was similar to that of SE rats. On the contrary, glabrous RFs on the noncasted forepaw of SR rats were larger than those on their casted forepaw. The size of hairy RFs was not altered by the forelimb restriction. Interestingly, alteration of the somatotopic features of the casted forepaw map persisted after 7 days of symmetric use of the forelimbs. The present study demonstrates that continuous sensory experience is needed for the organizational features of SI maps to be maintained.

Impact of neonatal asphyxia and hind limb immobilization on musculoskeletal tissues and S1 map organization: implications for cerebral palsy.

Cerebral palsy (CP) is a complex disorder of locomotion, posture and movements resulting from pre-, peri- or postnatal damage to the developing brain. In a previous study (Strata, F., Coq, J.O., Byl, N.N., Merzenich, M.M., 2004. Comparison between sensorimotor restriction and anoxia on gait and motor cortex organization: implications for a rodent model of cerebral palsy. Neuroscience 129, 141-156.), CP-like movement disorders were more reliably reproduced in rats by hind limb sensorimotor restriction (disuse) during development rather than perinatal asphyxia (PA). To gain new insights into the underpinning mechanisms of CP symptoms we investigated the long-term effects of PA and disuse on the hind limb musculoskeletal histology and topographical organization in the primary somatosensory cortex (S1) of adult rats. Developmental disuse (i.e. hind limb immobilization) associated with PA induced muscle fiber atrophy, extracellular matrix changes in the muscle, and mild to moderate ankle and knee joint degeneration at levels greater than disuse alone. Sensorimotor restricted rats with or without PA exhibited a topographical disorganization of the S1 cortical hind limb representation with abnormally large, multiple and overlapping receptive fields. This disorganization was enhanced when disuse and PA were associated. Altered cortical neuronal properties included increased cortical responsiveness and a decrease in neuronal selectivity to afferent inputs. These data support previous observations that asphyxia per se can generate the substrate for peripheral tissue and brain damage, which are worsened by aberrant sensorimotor experience during maturation, and could explain the disabling movement disorders observed in children with CP.

Acute reorganization of the forepaw representation in the rat SI cortex after focal cortical injury: neuroprotective effects of piracetam treatment

Immediate postlesion reorganization of the somatosensory cortical representation was examined in adult rats. Response properties of small clusters of neurons were recorded in the area of the primary somatosensory cortex (SI) devoted to the contralateral forepaw representation. Electrophysiological maps were elaborated on the basis of the sensory ‘submodality’ (cutaneous or noncutaneous) and the location of the peripheral receptive fields (RFs) of layer IV neurons. Recordings were made prior to, and from 1 to 12 h after, induction of a focal neurovascular lesion to the SI cortex that initially destroyed a part (8.5%) of the cutaneous representation. Moreover, the influence of an anti‐ischaemic substance (piracetam) on lesion‐induced changes was analysed. The main observations were: (i) a gradual outward expansion of the area of the functional lesion, which was smaller in the piracetam‐treated (PT) rats than in the control, placebo‐treated (PL) rats; (ii) a substantial remodelling of the spared representational zones, both in cortical sectors adjoining the site of injury and those remote from the site; (iii) a significant postlesion increase in the size of cutaneous RFs in the PT rats, but not in the PL rats; (iv) a better preservation of RF submodality and topographic organization in the PT maps than in the PL maps; and (v) a decrease in neuronal responsiveness to cutaneous stimulation which was less pronounced in the PT than in the PL rats. Our results can be ascribed to a rapid change in the balance of excitatory and inhibitory connections which leads to unmasking of subthreshold inputs converging onto cortical neurons. Our findings also indicate that acute piracetam treatment exerts a protective function on the physiological response properties of cortical neurons after focal injury.

Effects of sensorimotor restriction and anoxia on gait and motor cortex organization: Implications for a rodent model of cerebral palsy

Chronic or acute perinatal asphyxia (PA) has been correlated with the subsequent development of cerebral palsy (CP), a developmental neurological disorder characterized by spasticity and motor abnormalities often associated with cognitive deficits. Despite the prevalence of CP, an animal model that mimics the lifetime hypertonic motor deficits is still not available. In the present study, the consequences of PA on motor behavior, gait and organization of the primary motor cortex were examined in rats, and compared with the behavioral and neurological consequences of early postnatal movement-restriction with or without oxygen deprivation. Rats subjected to PA had mild increases in muscular tone accompanied by subtle differences in walking patterns, paralleled by significantly altered but relatively modest disorganization of their primary motor cortices. Movement-restricted rats, suffering PA or not, had reduced body growth rate, markedly increased muscular tone at rest and with active flexion and extension around movement-restricted joints that resulted in abnormal walking patterns and in a profoundly distorted representation of the hind limbs in the primary motor cortex. Within the sensorimotor-restricted groups, non-anoxic rats presented the most abnormal pattern and the greatest cortical representational degradation. This outcome further supports the argument that PA per se may represent a substrate for subtle altered motor behaviors, and that PA alone is sufficient to alter the organization of the primary motor cortex. At the same time, they also show that early experience-dependent movements play a crucial role in shaping normal behavioral motor abilities, and can make a powerful contribution to the genesis of aberrant movement abilities.

Peripheral and central changes combine to induce motor behavioral deficits in a moderate repetition task

Repetitive motion disorders, such as carpal tunnel syndrome and focal hand dystonia, can be associated with tasks that require prolonged, repetitive behaviors. Previous studies using animal models of repetitive motion have correlated cortical neuroplastic changes or peripheral tissue inflammation with fine motor performance. However, the possibility that both peripheral and central mechanisms coexist with altered motor performance has not been studied. In this study, we investigated the relationship between motor behavior changes associated with repetitive behaviors and both peripheral tissue inflammation and cortical neuroplasticity. A rat model of reaching and grasping involving moderate repetitive reaching with negligible force (MRNF) was used. Rats performed the MRNF task for 2 h/day, 3 days/week for 8 weeks. Reach performance was monitored by measuring reach rate/success, daily exposure, reach movement reversals/patterns, reach/grasp phase times, grip strength and grooming function. With cumulative task exposure, reach performance, grip strength and agility declined while an inefficient food retrieval pattern increased. In S1 of MRNF rats, a dramatic disorganization of the topographic forepaw representation was observed, including the emergence of large receptive fields located on both the wrist/forearm and forepaw with alterations of neuronal properties. In M1, there was a drastic enlargement of the overall forepaw map area, and of the cortex devoted to digit, arm-digits and elbow-wrist responses. In addition, unusually low current amplitude evoked digit movements. IL-1 beta and TNF-alpha increased in forearm flexor muscles and tendons of MRNF animals. The increases in IL-1 beta and TNF-alpha negatively correlated with grip strength and amount of current needed to evoke forelimb movements. This study provides strong evidence that both peripheral inflammation and cortical neuroplasticity jointly contribute to the development of chronic repetitive motion disorders.

Impact of prenatal ischemia on behavior, cognitive abilities and neuroanatomy in adult rats with white matter damage

Early brain damage, such as white matter damage (WMD), resulting from perinatal hypoxia-ischemia in preterm and low birth weight infants represents a high risk factor for mortality and chronic disabilities, including sensory, motor, behavioral and cognitive disorders. In previous studies, we developed a model of WMD based on prenatal ischemia (PI), induced by unilateral ligation of uterine artery at E17 in pregnant rats. We have shown that PI reproduced some of the main deficits observed in preterm infants, such as white and gray matter damage, myelination deficits, locomotor, sensorimotor, and short-term memory impairments, as well as related musculoskeletal and neuroanatomical histopathologies [1-3]. Here, we determined the deleterious impact of PI on several behavioral and cognitive abilities in adult rats, as well as on the neuroanatomical substratum in various related brain areas. Adult PI rats exhibited spontaneous exploratory and motor hyperactivity, deficits in information encoding, and deficits in short- and long-term object memory tasks, but no impairments in spatial learning or working memory in watermaze tasks. These results were in accordance with white matter injury and damage in the medial and lateral entorhinal cortices, as detected by axonal degeneration, astrogliosis and neuronal density. Although there was astrogliosis and axonal degeneration in the fornix, hippocampus and cingulate cortex, neuronal density in the hippocampus and cingulate cortex was not affected by PI. Levels of spontaneous hyperactivity, deficits in object memory tasks, neuronal density in the medial and lateral entorhinal cortices, and astrogliosis in the fornix correlated with birth weight in PI rats. Thus, this rodent model of WMD based on PI appears to recapitulate the main neurobehavioral and neuroanatomical human deficits often observed in preterm children with a perinatal history of ischemia.

Neuroanatomical, sensorimotor and cognitive deficits in adult rats with white matter injury following prenatal ischemia

Perinatal brain injury including white matter damage (WMD) is highly related to sensory, motor or cognitive impairments in humans born prematurely. Our aim was to examine the neuroanatomical, functional and behavioral changes in adult rats that experienced prenatal ischemia (PI), thereby inducing WMD. PI was induced by unilateral uterine artery ligation at E17 in pregnant rats. We assessed performances in gait, cognitive abilities and topographical organization of maps, and neuronal and glial density in primary motor and somatosensory cortices, the hippocampus and prefrontal cortex, as well as axonal degeneration and astrogliosis in white matter tracts. We found WMD in corpus callosum and brainstem, and associated with the hippocampus and somatosensory cortex, but not the motor cortex after PI. PI rats exhibited mild locomotor impairments associated with minor signs of spasticity. Motor map organization and neuronal density were normal in PI rats, contrasting with major somatosensory map disorganization, reduced neuronal density, and a marked reduction of inhibitory interneurons. PI rats exhibited spontaneous hyperactivity in open‐field test and short‐term memory deficits associated with abnormal neuronal density in related brain areas. Thus, this model reproduces in adult PI rats the main deficits observed in infants with a perinatal history of hypoxia‐ischemia and WMD.

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.