Neural networks and synaptic transmission in immature hippocampus

Abstract

The results reviewed in this chapter indicate that local circuit synaptic interactions are surprisingly well-developed in the rat hippocampal CA3 subfield during the second postnatal week. Intracellular recordings reveal large spontaneous epsps and ipsps. Synchronized bursts of synaptic potentials are observed in most paired intracellular recordings. Antidromic and orthodromic electrical stimulation evokes synaptic responses that are reminiscent of recordings from mature hippocampus. However, following brief trains of electrical stimuli and during bath application of a GABAA receptor antagonist, large prolonged depolarizations are recorded. These are suppressed by excitatory amino acid antagonists. In comparison, slices from mature rats do not produce these events under the same conditions. Thus, a hypothesis has been presented that the degree of recurrent synaptic interaction between pyramidal cells may be enhanced during this critical period in hippocampal development. An analysis of recurrent epsps using dual intracellular recordings is consistent with this contention. The degree of excitatory synaptic interaction between CA3 neurons appears to be at least equal to and likely in excess of that reported in mature hippocampus. One possible explanation for this is that the number of recurrent excitatory synapses may increase transiently during hippocampal development, only later to regress to numbers found in the adult. Recent studies of others suggest that activation of NMDA receptors may play a key role in the maintenance of synapses during development (Cline et al., 1987; Kleinschmidt et al., 1987). In this regard it is interesting that the characteristic of the NMDA receptor-ion channel complex on immature and mature rat CA3 hippocampal pyramidal cells appear to be quite different. These differences may play a role in synapse formation and maintenance. The role of NMDA receptors in LTP and learning (for review see Cotman et al., 1989; Lynch, 1986) are widely discussed. In other circles recurrent excitatory neuronal networks are thought to be substrates for memory (Lynch, 1986; Haberly and Bower, 1989). Both NMDA receptors and recurrent excitation are well represented in the CA3 subfield of immature hippocampus. One challenging area for future study will be the clarification of the interrelations between synaptogenesis and synaptic plasticity within neural networks of the developing hippocampus.