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Title: NMDA receptor blockade impairs the muscarinic conversion of sub-threshold transient depression into long-lasting LTD in the hippocampuseprefrontal cortex pathway in vivo: Correlation with gamma oscillations
Authors: Cleiton Lopes-Aguiar
Lezio Soares Bueno-Junior
Rafael Naime Ruggiero
Rodrigo Neves Romcy-Pereira
João Pereira Leite
Keywords: Muscarinic neurotransmission;NMDA;Hippocampus;Prefrontal cortex;Long-term depression (LTD);Synaptic Plasticity
Issue Date: 2013
Portuguese Abstract: Cholinergic fibers from the brainstem and basal forebrain innervate the medial prefrontal cortex (mPFC) modulating neuronal activity and synaptic plasticity responses to hippocampal inputs. Here, we investigated the muscarinic and glutamatergic modulation of long-term depression (LTD) in the intact projections from CA1 to mPFC in vivo. Cortical-evoked responses were recorded in urethaneanesthetized rats for 30 min during baseline and 4 h following LTD. In order to test the potentiating effects of pilocarpine (PILO), independent groups of rats received either a microinjection of PILO (40 nmol; i.c.v.) or vehicle, immediately before or 20 min after a sub-threshold LTD protocol (600 pulses, 1 Hz; LFS600). Other groups received either an infusion of the selective NMDA receptor antagonist (AP7; 10 nmol; intra-mPFC) or vehicle, 10 min prior to PILO preceding LFS600, or prior to a supra-threshold LTD protocol (900 pulses, 1 Hz; LFS900). Our results show that PILO converts a transient cortical depression induced by LFS600 into a robust LTD, stable for at least 4 h. When applied after LFS600, PILO does not change either mPFC basal neurotransmission or late LTD. Our data also indicate that NMDA receptor preactivation is essential to the muscarinic enhancement of mPFC synaptic depression, since AP7 microinjection into the mPFC blocked the conversion of transient depression into long-lasting LTD produced by PILO. In addition, AP7 effectively blocked the long-lasting LTD induced by LFS900. Therefore, our findings suggest that the glutamatergic co-activation of prefrontal neurons is important for the effects of PILO on mPFC synaptic depression, which could play an important role in the control of executive and emotional functions.
ISSN: 0028-3908
Appears in Collections:ICe - Artigos publicados em periódicos

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