Adenosine A₁ and A_2A receptors differently control synaptic plasticity in the mouse dorsal and ventral hippocampus

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 A_2A receptors (A₁ R and A_2A R) 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 A₁ R and A_2A R were more abundant in DH compared with VH. However, recordings of field excitatory postsynaptic potentials at Schaffer collaterals-CA1 pyramidal synapses revealed that A₁ R were equi-effective to inhibit basal excitatory synaptic transmission in DH and VH, but endogenous A₁ R activation was more effective to depress the probability of release in VH. In contrast, the selective A_2A R 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 A₁ R 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.