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Transl Psychiatry ; 8(1): 199, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30242146

RESUMO

Cholinergic basal forebrain (cBF)-derived neurotransmission plays a crucial role in regulating neuronal function throughout the cortex, yet the mechanisms controlling cholinergic innervation to downstream targets have not been elucidated. Here we report that removing the p75 neurotrophin receptor (p75NTR) from cBF neurons induces a significant impairment in fear extinction consolidation. We demonstrate that this is achieved through alterations in synaptic connectivity and functional activity within the medial prefrontal cortex. These deficits revert back to wild-type levels upon re-expression of the active domain of p75NTR in adult animals. These findings demonstrate a novel role for cholinergic neurons in fear extinction consolidation and suggest that neurotrophic signaling is a key regulator of cholinergic-cortical innervation and function.


Assuntos
Prosencéfalo Basal/citologia , Prosencéfalo Basal/metabolismo , Neurônios Colinérgicos/citologia , Neurônios Colinérgicos/metabolismo , Extinção Psicológica/fisiologia , Medo/fisiologia , Consolidação da Memória/fisiologia , Receptores de Fator de Crescimento Neural/metabolismo , Animais , Axônios , Feminino , Masculino , Camundongos Knockout , Vias Neurais/citologia , Vias Neurais/metabolismo , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/metabolismo
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