EFFECT OF GABA(B) RECEPTORS ON SYNAPTIC-INTERACTIONS IN DENTATE GYRUSGRANULE NEURONS OF THE RAT

Dendritic arborization permits convergence of synaptic inputs and thei r integration in single neurons. The granule neuron in the dentate gyr us represents a relatively simple example where anatomically and funct ionally distinct medial and lateral perforant pathways terminate on di fferent regions of the dendritic tree. High-frequency stimulation of e ither pathway alone results in the induction of long-term potentiation . However, whether the potentiated synapses in different parts of the dendrites interact is not known. In this study we have compared long-t erm potentiation and synaptic interactions in the lateral and medial p erforant pathways in the ''disinhibited'' hippocampal slice preparatio n in the presence of the GABA(A) receptor blocker bicuculline. The dat a show that the magnitude of long-term potentiation induced by tetanic stimulation was similar in both pathways, but differences between the two pathways were revealed after two or more tetanizations. A signifi cantly smaller capacity for further long-term potentiation in the late ral, as compared to the medial, perforant pathway was found and can be attributed to stronger postsynaptic GABA(B) inhibition in distal dend rites of granule neurons. Blockade of GABA(B) inhibition with CGP36742 (100 mu M) unmasked additional long-term potentiation in the lateral pathway. Presynaptically, GABA(B) receptors produced a short-lasting h eterosynaptic depression in the medial pathway, which was reduced by C GP36742. Coincident activation of the two pathways boosted long-term p otentiation only in the medial pathway. We propose that the interactio ns between the two pathways are orchestrated to maximize associative l ong-term potentiation in the medial pathway; this may be important for types of learning attributed to the hippocampus. (C) 1997 IBRO.