Autor(es):
Kerkhofs, Amber ; Canas, Paula M. ; Timmerman, A. J. ; Heistek, Tim S. ; Real, Joana I. ; Xavier, Carolina ; Cunha, Rodrigo A. ; Mansvelder, Huibert D. ; Ferreira, Samira G.
Data: 2018
Identificador Persistente: https://hdl.handle.net/10316/107632
Origem: Estudo Geral - Universidade de Coimbra
Projeto/bolsa:
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/PT;
Assunto(s): A2A receptor; prefrontal cortex (PFC); synaptic plasticity; fast-spiking interneurons; adenosine; LTP and LTD; electrophysiology
Descrição
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.
Supported by Maratona da Saúde, Santa Casa da Misericórdia, GAI-FMUC and Banco Santander-Totta, NARSAD, Erasmus Mundus Joint Doctorate grant (ENC-Network) and ERDF, through Centro 2020 (project no. CENTRO-01-0145-FEDER- 000008:BrainHealth 2020), and through FCT (project nos. POCI- 01-0145-FEDER-007440 and PTDC/NEU-NMC/4154/2016) to RC. HM received funding for this work from the Netherlands Organization for Scientific Research (NWO; VICI grant), ERC StG “BrainSignals,” EU H2020 Framework Program (agreement no. 604102 “Human Brain Project”) and the EU 7th Framework Program (no. EU MSCA-ITN CognitionNet FP7-PEOPLE-2013- ITN 607508).
