MODULATION OF SYNAPTIC TRANSMISSION BY ADENOSINE IN LAYER 2/3 OF THE RAT VISUAL CORTEX IN VITRO

Adenosine is a wide-spread endogenous neuromodulator. In the central nervous system it activates A(1) and A(2A) receptors (A1Rs and A(2A)Rs) which have differential distributions, different affinities to adenosine, are coupled to different G-proteins, and have opposite effects on synaptic transmission. Although effects of adenosine are studied in detail in several brain areas, such as the hippocampus and striatum, the heterogeneity of the effects of A(1)R and A(2A)R activation and their differential distribution preclude generalization over brain areas and cell types. Here we study adenosine's effects on excitatory synaptic transmission to layer 2/3 pyramidal neurons in slices of the rat visual cortex. We measured effects of bath application of adenosine receptor ligands on evoked excitatory postsynaptic potentials (EPSPs), miniature excitatory postsynaptic potentials (mEPSPs), and membrane properties. Adenosine reduced the amplitude of evoked EPSPs and excitatory postsynaptic currents (EPSCs), and reduced frequency of mEPSPs in a concentration-dependent and reversible manner. Concurrent with EPSP/C amplitude reduction was an increase in the paired-pulse ratio. These effects were blocked by application of the selective A(1)R antagonist DPCPX (8-cyclopentyl- 1,3-dipropylxanthine), suggesting that activation of presynaptic A(1)Rs suppresses excitatory transmission by reducing release probability. Adenosine (20 mu M) hyperpolarized the cell membrane from -65.3 +/- 1.5 to -67.7 +/- 1.8 mV, and reduced input resistance from 396.5 +/- 44.4 to 314.0 +/- 36.3 MOhm (similar to 0%). These effects were also abolished by DPCPX, suggesting postsynaptic A(1)Rs. Application of the selective A(2A)R antagonist SCH-58261 (2-(2furanyl)- 7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4] triazolo[ 1,5-c] pyrimidin-5-a-mine) on the background of high adenosine concentrations revealed an additional decrease in EPSP amplitude. Moreover, application of the A(2A)R agonist CGS-21680 (4-[2-[[6-amino-9-(N-ethyl-b-D-ribofuranuronamidosyl)- 9H-purin-2-yl] amino] ethyl] benzenepropanoic acid hydrochloride) led to an A(1)R-dependent increase in mEPSP frequency. Dependence of the A(2A)R effects on the A(1)R availability suggests interaction between these receptors, whereby A(2A)Rs exert their facilitatory effect on synaptic transmission by inhibiting the A(1)R-mediated suppression. Our results demonstrate functional pre and postsynaptic A(1)Rs and presynaptic A(2A)Rs in layer 2/3 of the visual cortex, and suggest interaction between presynaptic A(2A)Rs and A(1)Rs. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.