Cooperative changes in GABA, glutamate and activity levels: the missing link in cortical plasticity

Different intracortical mechanisms have been reported to contribute to the substantial topographic reorganization of the mammalian primary visual cort ex in response to matching lesions in the two retinas: an immediate expansi on of receptive fields followed by a gradual shift of excitability into the deprived area and finally axonal sprouting of laterally projecting neurons months after the lesion. To gain insight into the molecular mechanisms of this adult plasticity, we used immunocytochemical and bioanalytical methods to measure the glutamate and GABA neurotransmitter levels in the visual co rtex of adult cats with binocular central retinal lesions. Two to four week s after the lesions, glutamate immunoreactivity was decreased in sensory-de prived cortex as confirmed by HPLC analysis of the glutamate concentration. Within three months normal glutamate immunoreactivity was restored. In add ition, the edge of the unresponsive cortex was characterized by markedly in creased glutamate immunoreactivity 2-12 weeks postlesion. This glutamate im munoreactivity peak moved into the deprived area over time. These glutamate changes corresponded to decreased spontaneous and visually driven activity in unresponsive cortex and to,strikingly increased neuronal activity at th e border of this cortical zone. Furthermore, the previously reported decrea se in glutamic acid decarboxylase immunoreactivity was found to reflect dec reased GABA levels in sensory-deprived cortex. Increased glutamate concentr ations and neuronal activity, and decreased GABA concentrations, may be rel ated to changes in synaptic efficiency and could represent a mechanism unde rlying the retinotopic reorganization that occurs well after the immediate receptive field expansion but long before the late axonal sprouting.