Adenosine A2A receptors control glutamatergic synaptic plasticity in fast spiking interneurons of the prefrontal cortex

Amber Kerkhofs, Paula M. Canas, A. J. Timmerman, Tim S. Heistek, Joana I. Real, Carolina Xavier, Rodrigo A. Cunha, Huibert D. Mansvelder, Samira G. Ferreira*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Adenosine A2A receptors (A2AR) are activated upon increased synaptic activity to assist in the implementation of long-term plastic changes at synapses. While it is reported that A2AR 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 A2AR control glutamatergic synapse plasticity within the medial PFC (mPFC). To elucidate that, we tested whether A2AR 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 A2AR 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 A2AR blockade. The interneuron-specificity of A2AR in controlling glutamatergic synapse LTP may ensure that during periods of high synaptic activity, a proper excitation/inhibition balance is maintained within the mPFC.

Original languageEnglish
Article number133
Pages (from-to)1-12
Number of pages12
JournalFrontiers in Pharmacology
Issue number20 March
Publication statusPublished - 20 Mar 2018


FundersFunder number
Seventh Framework Programme607508, 604102


    • A receptor
    • Adenosine
    • Electrophysiology
    • Fast-spiking interneurons
    • LTP and LTD
    • Prefrontal cortex (PFC)
    • Synaptic plasticity


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