Adenosine A1 and A2A receptors differently control synaptic plasticity in the mouse dorsal and ventral hippocampus

Abstract

The hippocampus is a brain region involved in processing both memory and emotions, through a preferential involvement of the dorsal hippocampus (DH) and ventral hippocampus (VH), respectively. Adenosine A1 and A2A receptors (A1R and A2AR) control both mood and memory, but it is not known if there is a different adenosine modulation of synaptic plasticity along the hippocampal axis. Using adult, C57BL/6 male mice, we show that both A1R and A2AR were more abundant in DH compared with VH. However, recordings of field excitatory postsynaptic potentials at Schaffer collaterals-CA1 pyramidal synapses revealed that A1R were equi-effective to inhibit basal excitatory synaptic transmission in DH and VH, but endogenous A1R activation was more effective to depress the probability of release in VH. In contrast, the selective A2AR antagonist (SCH58261, 50 nM) controlled both long-term potentiation (induced by a high frequency stimulation protocol) and long-term depression (induced by a low frequency stimulation protocol) selectively in DH rather than VH, whereas the selective A1R antagonist (DPCPX, 100 nM) revealed a similar tonic inhibition of long-term depression in DH and VH. These findings show a different control of synaptic plasticity by the adenosine modulation system in the dorsal and ventral poles of the hippocampus, which may underlie a different efficiency of the adenosine system to control mood and memory. (Figure presented.).