Adenosine A 2A Receptors Control Glutamatergic Synaptic Plasticity in Fast Spiking Interneurons of the Prefrontal Cortex.

Adenosine A(2A) receptors (A(2A)R) are activated upon increased synaptic activity to assist in the implementation of long-term plastic changes at synapses. While it is reported that A(2A)R are involved in the control of prefrontal cortex (PFC)-dependent behavior such as working memory, reversal learning and effort-based decision making, it is not known whether A(2A)R control glutamatergic synapse plasticity within the medial PFC (mPFC). To elucidate that, we tested whether A(2A)R blockade affects long-term plasticity (LTP) of excitatory post-synaptic potentials in pyramidal neurons and fast spiking (FS) interneurons in layer 5 of the mPFC and of population spikes. Our results show that A(2A)R are enriched at mPFC synapses, where their blockade reversed the direction of plasticity at excitatory synapses onto layer 5 FS interneurons from LTP to long-term depression, while their blockade had no effect on the induction of LTP at excitatory synapses onto layer 5 pyramidal neurons. At the network level, extracellularly induced LTP of population spikes was reduced by A(2A)R blockade. The interneuron-specificity of A(2A)R in controlling glutamatergic synapse LTP may ensure that during periods of high synaptic activity, a proper excitation/inhibition balance is maintained within the mPFC.