Age-dependent regulation of GABAA receptors in neocortex

We have shown previously that GABAA receptors labelled with the antagonist [3H]SR95531 can be regulated in a living cortical slice preparation by agonists or changes in electrical activity. Due to the important role that receptor regulation may play in controlling neural activity, we have now investigated the regulation of GABAA receptors in neocortex at different stages in postnatal life. We found that regulation by agonist stimulation and increases in bioelectric activity is age-dependent in amount and, in the latter case, in direction. Using muscimol as an agonist we observed a GABAA receptor down-regulation of between 60 and 70% at 20-30 days of age; in adults muscimol gave an 11% down-regulation. A combination of veratridine and glutamate gave a peak down-regulation of 39% at 20 days postnatal, but an up-regulation of 58% in adults. These age-dependent effects may signal a role for receptor regulation in cortical neural critical period plasticity.