SPONTANEOUS ACTIVITY AND RECURRENT INHIBITION IN CULTURED HIPPOCAMPALNETWORKS

As a model for an integrated neuronal network based on the concept of modular units, we have investigated the occurrence of spontaneous acti vity and the formation of synaptic circuits in primary cultures of dis sociated hippocampal neurons from the embryonic rat. Sodium-dependent action potentials (APs) could be elicited after 1 day in vitro (DIV), whereas spontaneous postsynaptic potentials (PSPs), ''miniature'' PSPs and APs appeared after 3-6 DIV. The number of cells with spontaneous APs and the rate of APs increased during development of the neuritic n etwork. In addition to a stochastic spike interval distribution, pyram id-shaped neurons could be identified after 10-12 DIV, which fired pre ferentially at interspike intervals between 20-120 ms and 190-400 ms. This distinctive bimodal interspike interval pattern was sensitive to GABA-A antagonists. Simultaneous recordings of pairs of neurons demons trated recurrent inhibitory, GABA-ergic synaptic circuits. In addition , a subpopulation of GABAergic neurons could be visualized by immunocy tochemistry. These results are discussed in relation to the hypothesis that spontaneous firing of connected neurons is network-driven, based on synaptic ''noise'' and patterned by recurrent inhibition. (C) 1993 Wiley-Liss, Inc.