Recovery of evoked potentials, metabolic activity and behavior in a mouse model of somatosensory cortex lesion: role of the neural cell adhesion molecule (NCAM).

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.

Comparative study of the neuronal plasticity along the neuraxis of the vibrissal sensory system of adult rat following unilateral infraorbital nerve damage and subsequent regeneration.

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.

Does the cortical representation of body parts follow both injury to the related sensory peripheral nerve and its regeneration?

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.

Stimulus-dependent muscarinic effects on evoked unit activity in the rat barrel cortex.

The cerebral cortex receives a prominent cholinergic innervation, which is thought to play an important role in the regulation of its normal function. Electrophysiological studies have shown that activation of muscarinic cholinergic receptors results in a marked enhancement of excitatory stimuli onto cortical neurons. In the present study, we examined the effects of acetylcholine (ACh) and its muscarinic agonists (applied by pressure injection) on the response components of individual cortical neurons in layers IV and V of the rat somatosensory cortex in identified barrels (C2 and C3). It was found that the muscarinic agonists could modify the evoked unit activity (in most cases, they caused units to respond to previously minimally effective whisker stimuli), but the modulatory effect was highly dependent on the stimulus parameters, and in most cases, the effect was limited to only one component of 'on' or 'off' responses consisting of 2-4 spikes.

Muscarinic cholinergic effects on stimulus-evoked responses in rat primary somatosensory cortex. An electrophysiological study.

Neuron terminals originating from the nucleus basalis megnocellularis (NBM) are the major source of the cortical cholinergic innervation, which is thought to play an essential role in higher brain functions. Electrophysiological studies have shown that activation of muscarinic cholinergic receptors caused a marked enhancement of sensory stimuli onto cortical neurons. Diminished cholinergic innervation of somatosensory cortical areas are manifested in decreased stimulus-evoked activity and impaired performance in a sensory discrimination task. We examined the effects of ACh and its muscarinic agonists on the response properties of layer IV-V barrel cortex neurons evoked by precisely controlled vibriasa deflections. The cholinergic pharmacons displayed their mostly facilitatory effects in latency-dependent manner: In most cases only one latency component of On and/or Off responses were changed.