α2* Nicotinic acetylcholine receptors influence hippocampus-dependent learning and memory in adolescent mice

• Autores: Lotfipour, Shahrdad; Mojica, Celina; Nakauchi, Sakura; Lipovsek, Maria Marcela; Silverstein, Sarah; Cushman, Jesse; Tirtorahardjo, James; Poulos, Andrew; Elgoyhen, Ana Belen; Sumikawa, Katumi; Fanselow, Michael S.; Boulter, Jim
• Año de publicación: 2017
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Receptores Nicotínicos; Canales Iónicosaddicción
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

The absence of α2* nicotinic acetylcholine receptors (nAChRs) in oriens lacunosum moleculare (OLM) GABAergic interneurons ablate the facilitation of nicotine-induced hippocampal CA1 long-term potentiation and impair memory. The current study delineated whether genetic mutations of α2* nAChRs (Chrna2L9′S/L9′S and Chrna2KO) influence hippocampus-dependent learning and memory and CA1 synaptic plasticity. We substituted a serine for a leucine (L9′S) in the α2 subunit (encoded by the Chrna2 gene) to make a hypersensitive nAChR. Using a dorsal hippocampus-dependent task of preexposure-dependent contextual fear conditioning, adolescent hypersensitive Chrna2L9′S/L9′S male mice exhibited impaired learning and memory. The deficit was rescued by low-dose nicotine exposure. Electrophysiological studies demonstrated that hypersensitive α2 nAChRs potentiate acetylcholine-induced ion channel flux in oocytes and acute nicotine-induced facilitation of dorsal/intermediate CA1 hippocampal long-term potentiation in Chrna2L9′S/L9′S mice. Adolescent male mice null for the α2 nAChR subunit exhibited a baseline deficit in learning that was not reversed by an acute dose of nicotine. These effects were not influenced by locomotor, sensory or anxiety-related measures. Our results demonstrated that α2* nAChRs influenced hippocampus-dependent learning and memory, as well as nicotine-facilitated CA1 hippocampal synaptic plasticity.
Fil: Lotfipour, Shahrdad. University of California at Los Angeles; Estados Unidos
Fil: Mojica, Celina. University of California at Los Angeles; Estados Unidos
Fil: Nakauchi, Sakura. University of California at Irvine; Estados Unidos
Fil: Lipovsek, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina
Fil: Silverstein, Sarah. University of California at Los Angeles; Estados Unidos
Fil: Cushman, Jesse. University of California at Los Angeles; Estados Unidos
Fil: Tirtorahardjo, James. University of California at Irvine; Estados Unidos
Fil: Poulos, Andrew. University of California at Los Angeles; Estados Unidos. State University of New York; Estados Unidos
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina
Fil: Sumikawa, Katumi. University of California at Irvine; Estados Unidos
Fil: Fanselow, Michael S.. University of California at Los Angeles; Estados Unidos
Fil: Boulter, Jim. University of California at Los Angeles; Estados Unidos