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

LOTFIPOUR, SHAHRDAD; MOJICA, CELINA; NAKAUCHI, SAKURA; LIPOVSEK, MARCELA; SILVERSTEIN, SARAH; CUSHMAN, JESSE; TIRTORAHARDJO, JAMES; POULOS, ANDREW; ELGOYHEN, ANA BELÉN; SUMIKAWA, KATUMI; FANSELOW, MICHAEL S.; BOULTER, JIM

Learning & Memory

CSH press

Lugar: New York; Año: 2017 vol. 24 p. 231 - 244

The absence of a2∗ 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. Thecurrent study delineated whether genetic mutations of a2∗ 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 a2 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 a2 nAChRs potentiate acetylcholine-induced ion channel flux in oocytes and acute nicotineinduced facilitation of dorsal/intermediate CA1 hippocampal long-term potentiation in Chrna2L9′S/L9′S mice. Adolescent male mice null for the a2 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 a2∗ nAChRs influenced hippocampus-dependent learning and memory, as well as nicotine-facilitated CA1 hippocampal synaptic plasticity.