MORPHOLOGICAL CORRELATES OF ALTERED NEURONAL-ACTIVITY IN ORGANOTYPIC CEREBELLAR CULTURES CHRONICALLY EXPOSED TO ANTI-GABA AGENTS

Organotypic cerebellar cultures derived from newborn mice were chronic ally exposed to medium containing picrotoxin or bicuculline from expla ntation until they were recorded from extracellularly or fixed for mor phological studies. Cultures exposed to anti-GABA agents for 13-18 day s in vitro had decreased spontaneous cortical discharge rates when com pared with sister control cultures and prolonged inhibitory responses to cortical stimulation. Electron microscopic examination of exposed c ultures after 14-16 days in vitro revealed a hyperinnervation of Purki nje cell somata by inhibitory terminals predominantly of basket cell o rigin. The sprouted terminals penetrated otherwise intact Purkinje cel l astrocytic sheaths. These changes represent a departure from the usu al developmental pattern, a departure induced by exposure to anti-GABA agents that increased neuronal activity early in the development of t he cerebellar circuitry in vitro. The precise signals that initiated t he changes are unknown, but the altered development is most likely in response to increased Purkinje cell activity.