Effect of GABA(B) receptors on synaptic interactions in dentate gyrus granule neurons of the rat.

Dendritic arborization permits convergence of synaptic inputs and their integration in single neurons. The granule neuron in the dentate gyrus represents a relatively simple example where anatomically and functionally distinct medial and lateral perforant pathways terminate on different regions of the dendritic tree. High-frequency stimulation of either 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-term potentiation and synaptic interactions in the lateral and medial perforant pathways in the "disinhibited" hippocampal slice preparation in the presence of the GABA(A) receptor blocker bicuculline. The data 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 significantly smaller capacity for further long-term potentiation in the lateral, as compared to the medial, perforant pathway was found and can be attributed to stronger postsynaptic GABA(B) inhibition in distal dendrites of granule neurons. Blockade of GABA(B) inhibition with CGP36742 (100 microM) unmasked additional long-term potentiation in the lateral pathway. Presynaptically, GABA(B) receptors produced a short-lasting heterosynaptic depression in the medial pathway, which was reduced by CGP36742. Coincident activation of the two pathways boosted long-term potentiation only in the medial pathway. We propose that the interactions between the two pathways are orchestrated to maximize associative long-term potentiation in the medial pathway; this may be important for types of learning attributed to the hippocampus.