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.