MAJOR DORSOVENTRAL DIFFERENCES IN THE MODULATION OF THE LOCAL CA1 HIPPOCAMPAL NETWORK BY NMDA, mGlu5, ADENOSINE A2A AND CANNABINOID CB1 RECEPTORS

Recent research points to diversification in the local neuronal circuitry between dorsal (DH) and ventral (VH) hippocampus that may be involved in the large-scale functional segregation along the long axis of the hippocampus. Here, using CA1 field recordings from rat hippocampal slices, we show that activation of N-methyl-D-aspartate receptors (NMDARs) reduced excitatory transmission more in VH than in DH, with an adenosine A(1) receptor-independent mechanism, and reduced inhibition and enhanced postsynaptic excitability only in DH. Strikingly, co-activation of metabotropic glutamate receptor-5 (mGluR5) with NMDAR, by CHPG and NMDA respectively, strongly potentiated the effects of NMDAR in DH but had not any potentiating effect in VH. Furthermore, the synergistic actions in DH were occluded by blockade of adenosine A(2A) receptors (A(2A)Rs) by their antagonist ZM 241385 demonstrating a tonic action of these receptors in DH. Exogenous activation of A(2A)Rs by 4-[2-[[6-amino-9-(N-ethyl-beta-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid hydrochloride (CGS 21680) did not change the effects of mGluR5-NMDAR co-activation in either hippocampal pole. Importantly, blockade of cannabinoid CB1 receptors (CB(1)Rs) by their antagonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide (AM 281) restricted the synergistic actions of mGluR5-NMDARs on excitatory synaptic transmission and postsynaptic excitability and abolished their effect on inhibition. Furthermore, AM 281 increased the excitatory transmission only in DH indicating that CB(1)Rs were tonically active in DH but not VH. Removing the magnesium ions from the perfusion medium neither stimulated the interaction between mGluR5 and NMDAR in VH nor augmented the synergy of the two receptors in DH. These findings show that the NMDAR-dependent modulation of fundamental parameters of the local neuronal network, by mGluR5, A(2A)R and CB1R, markedly differs between DH and VH. We propose that the higher modulatory role of A(2A)R and mGluR5, in combination with the role of CB(1)Rs, provide DH with higher functional flexibility of its NMDARs, compared with VH. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.