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 A1 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 A2A receptors (A2ARs) by their antagonist ZM 241385 demonstrating a tonic action of these receptors in DH. Exogenous activation of A2ARs by 4-[2-[[6-amino-9-(N-ethyl-β-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 (CB1Rs) 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 CB1Rs 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, A2AR and CB1R, markedly differs between DH and VH. We propose that the higher modulatory role of A2AR and mGluR5, in combination with the role of CB1Rs, provide DH with higher functional flexibility of its NMDARs, compared with VH.
['Kouvaros|S|S|', 'Papatheodoropoulos|C|C|']
D000818:Animals D001703:Biophysics D056547:CA1 Region, Hippocampal D063385:Cannabinoid Receptor Modulators D004357:Drug Synergism D004558:Electric Stimulation D018683:Excitatory Amino Acid Agents D018690:Excitatory Amino Acid Agonists D019706:Excitatory Postsynaptic Potentials D066298:In Vitro Techniques D008297:Male D009025:Morpholines D016202:N-Methylaspartate D058905:Purinergic Agents D011720:Pyrazoles D051381:Rats D017208:Rats, Wistar D043705:Receptor, Adenosine A2A D043884:Receptor, Cannabinoid, CB1 D064529:Receptor, Metabotropic Glutamate 5 D018709:Statistics, Nonparametric
dorsoventral hippocampus A(2A) receptor CB(1) receptor NMDA receptor mGlu5 receptor