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Neural Plast ; 2015: 472676, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26113994

RESUMO

Striatal projection neurons (SPNs) process motor and cognitive information. Their activity is affected by Parkinson's disease, in which dopamine concentration is decreased and acetylcholine concentration is increased. Acetylcholine activates muscarinic receptors in SPNs. Its main source is the cholinergic interneuron that responds with a briefer latency than SPNs during a cortical command. Therefore, an important question is whether muscarinic G-protein coupled receptors and their signaling cascades are fast enough to intervene during synaptic responses to regulate synaptic integration and firing. One of the most known voltage dependent channels regulated by muscarinic receptors is the KV7/KCNQ channel. It is not known whether these channels regulate the integration of suprathreshold corticostriatal responses. Here, we study the impact of cholinergic muscarinic modulation on the synaptic response of SPNs by regulating KV7 channels. We found that KV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines compartment. In contrast, it is negligible in the somatic compartment. This modulation occurs on sub- and suprathreshold responses and lasts during the whole duration of the responses, hundreds of milliseconds, greatly altering SPNs firing properties. This modulation affected the behavior of the striatal microcircuit.


Assuntos
Potenciais de Ação , Neurônios GABAérgicos/fisiologia , Canais de Potássio KCNQ/fisiologia , Neostriado/fisiologia , Sinapses/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Córtex Cerebral/fisiologia , Neurônios Colinérgicos/fisiologia , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Neurônios GABAérgicos/citologia , Neurônios GABAérgicos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos Transgênicos , Muscarina/farmacologia , Agonistas Muscarínicos/farmacologia , Neostriado/citologia , Neostriado/metabolismo , Peptídeos/farmacologia , Receptor Muscarínico M1/agonistas , Receptor Muscarínico M1/antagonistas & inibidores , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo
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