Abstract
Experience-induced plastic changes in the cerebral cortex are accompanied by alterations in excitatory and inhibitory transmission. Increased excitatory drive, necessary for plasticity, precedes the occurrence of plastic change, while decreased inhibitory signaling often facilitates plasticity. However, an increase of inhibitory interactions was noted in some instances of experience-dependent changes. We previously reported an increase in the number of inhibitory markers in the barrel cortex of mice after fear conditioning engaging vibrissae, observed concurrently with enlargement of the cortical representational area of the row of vibrissae receiving conditioned stimulus (CS). We also observed that an increase of GABA level accompanied the conditioning. Here, to find whether unaltered GABAergic signaling is necessary for learning-dependent rewiring in the murine barrel cortex, we locally decreased GABA production in the barrel cortex or reduced transmission through GABAA receptors (GABAARs) at the time of the conditioning. Injections of 3-mercaptopropionic acid (3-MPA), an inhibitor of glutamic acid decarboxylase (GAD), into the barrel cortex prevented learning-induced enlargement of the conditioned vibrissae representation. A similar effect was observed after injection of gabazine, an antagonist of GABAARs. At the behavioral level, consistent conditioned response (cessation of head movements in response to CS) was impaired. These results show that appropriate functioning of the GABAergic system is required for both manifestation of functional cortical representation plasticity and for the development of a conditioned response.
Highlights
Associative learning results in functional changes in the neuronal networks of the brain cortex
We found that reducing gamma-aminobutyric acid (GABA) synthesis or GABAergic signaling in the barrel cortex by blocking glutamic acid decarboxylase (GAD) activity or GABAARs (GABAA receptors) prevented the development of cortical representation plastic change
We found that transient reduction of GABA level and GABAergic transmission locally in the area of the barrel cortex, blocked plastic changes induced by conditioning
Summary
Associative learning results in functional changes in the neuronal networks of the brain cortex. The pairing of vibrissae stimulation with a tail shock results in enlargement of the functional cortical representation of the stimulated whiskers, visualized by [14C]2-deoxyglucose mapping. We previously reported that enlargement of the cortical representation of vibrissae involved in conditioning was NMDA receptor dependent [7] and accompanied by increased excitability of projection neurons [8]. With the above results, we found an increased density of GABA immunoreactive cells in layer IV of the cortical representation of conditioned vibrissae [11], and an increase of GABA level in the barrel cortex [12]. Learning resulted in a 70% increase in the density of inhibitory synapses on dendritic spines, with higher GABA content in their presynaptic terminals [13]. We found that conditioning resulted in an increase in the frequency of spontaneous inhibitory postsynaptic currents and inhibitory tonic currents in excitatory neurons, with a simultaneous decrease of the latter in fast-spiking inhibitory interneurons [14,15]
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