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 cortex in response to matching lesions in the two retinas: an immediate expansion 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 cortex of adult cats with binocular central retinal lesions. Two to four weeks after the lesions, glutamate immunoreactivity was decreased in sensory-deprived cortex as confirmed by HPLC analysis of the glutamate concentration. Within three months normal glutamate immunoreactivity was restored. In addition, the edge of the unresponsive cortex was characterized by markedly increased glutamate immunoreactivity 2-12 weeks postlesion. This glutamate immunoreactivity 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 the border of this cortical zone. Furthermore, the previously reported decrease in glutamic acid decarboxylase immunoreactivity was found to reflect decreased GABA levels in sensory-deprived cortex. Increased glutamate concentrations and neuronal activity, and decreased GABA concentrations, may be related to changes in synaptic efficiency and could represent a mechanism underlying the retinotopic reorganization that occurs well after the immediate receptive field expansion but long before the late axonal sprouting.
Arckens
L
L
Laboratory of Neuroendocrinology and Immunological Biotechnology, Katholieke Universiteit Leuven, Naamsestraat 59, B-3000 Leuven, Belgium. Lut.Arckens@BIO.KULeuven.ac.be
Schweigart
G
G
Qu
Y
Y
Wouters
G
G
Pow
D V
DV
Vandesande
F
F
Eysel
U T
UT
Orban
G A
GA
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002415:Cats; D004594:Electrophysiology / Q000379:methods; D005074:Evoked Potentials, Visual; D007839:Functional Laterality; D018698:Glutamic Acid / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010775:Photic Stimulation; D012160:Retina / Q000502:physiology*; D013997:Time Factors; D014793:Visual Cortex / Q000166:cytology / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid