Understanding the processes that underlie functional recovery after cortical injury is a major challenge for neurobiology and clinical neurology. The aim of the present study was to establish a mouse model of functional recovery that would facilitate the investigation of the molecular and cellular events involved in cortical dynamics. We show that a focal injury of approximately 0.5 mm of diameter and 1 mm depth made in the barrel cortex of adult mice induced a transitory deficit that could be characterized using somatosensory evoked potential (SEP), metabolic mapping and a behavioral test. SEP recordings of short latency responses using an epicranial multi-array system showed a decreased cortical activity in the peri-lesion regions 2 weeks after the injury and a partial recovery to normal pattern 6 weeks after the lesion. Delayed SEP signals over the motor cortex were not altered by the injury. Metabolic mapping with [14C]deoxyglucose uptake in the surround of the injury reproduced the time course of deficit and recovery. Finally, a deficit in vibrissae related performance in a gap-crossing test 1 week after injury was followed by a functional recovery in the following 2 weeks. We show in addition that the recovery process is deficient and significantly delayed in NCAM knockout mice lacking all isoforms of NCAM (neural cell adhesion molecule)and PSA-NCAM. These results support the hypothesis that impairment and recovery of functions after focal cortical lesion involves remodeling of intact circuits surrounding the lesion and that the NCAM molecule participate in this process. The model opens new possibilities for investigating the role of candidate molecules in functional recovery using genetically modified mice.
The aim of the present study was to examine the physiological consequences of a unilateral infraorbital nerve lesion and its regeneration at different levels of the somatosensory neuraxis. In animals whose right infraorbital nerve had been crushed, a large unresponsive area was found in the main brainstem trigeminal nucleus (Pr5). Responses evoked by ipsilateral vibrissal deflection in the middle of Pr5 reappeared only on days 22-35 after the nerve had been transected, whereas recovery from the nerve crush took only 7-9 days. However, no sign of short-term neuronal plasticity was observed in Pr5 after peripheral nerve injury. An enlargement of the receptive fields in two-thirds of the units and a lengthening in the delay of the evoked responses were observed as long-term plastic changes in Pr5 neurons after peripheral-nerve regeneration. In the ventral posteromedial nucleus of the thalamus (VPM) of partly denervated animals, however, only minutes or hours after the nerve crush, certain units were found to respond in some cases not only to the vibrissae, but also to mechanical stimulation of the face over the eye (two units), the nose (one unit), and the midline (one unit). Apart from the experiments involving incomplete denervation, the vibrissal representation areas of the VPM were unresponsive to stimulation of both the vibrissae and other parts of the face until nerve regeneration had occurred. In the somatosensory cortex, an infraorbital nerve crush immediately resulted in a large cortical area being unresponsive to vibrissal deflection. It was noteworthy, however, that shortly after the nerve crush, this large unresponsive whisker representation cortical area was invaded from the rostromedial direction by responses evoked by stimulation of the forepaw digits. In spite of the reappearance of vibrissa-evoked responses 7-10 days after the nerve crush, an expanded digital representation could still be observed 3 weeks after the nerve crush, resulting in an overlapping area of digital and vibrissal representations. The withdrawal of the expanded representation of forepaw digits was completed by 60 days after the nerve crush. The results obtained in Pr5, the VPM, and the cortex strongly suggest that the higher the station in the neuraxis, the greater the degree of plasticity after infraorbital nerve injury.
A study was made of the borderline between the physiological representations of the digits (D2, D3 and D4) and sinus whiskers in the rat primary somatosensory cortex after a contralateral infraorbital nerve crush. Following the injury, the physiological representation of the digits of the contralateral forepaw extended posterolaterally, occupying the anterolateral part of the whisker region (posteromedial barrel subfield). The extended physiological representation of the digits, though somewhat shrunken, remained after the reappearance of whisker-evoked responses, forming an overlapping area between the obligate digit and whisker representations. The findings emphasize the importance of afferent inputs in modulating cortical organization, but show that a reversible change in a sensory input (nerve damage) does not result in a perfectly reversible change in cortical representation.
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