| First Author | Lotfipour S | Year | 2017 |
| Journal | Learn Mem | Volume | 24 |
| Issue | 6 | Pages | 231-244 |
| PubMed ID | 28507032 | Mgi Jnum | J:272596 |
| Mgi Id | MGI:6285265 | Doi | 10.1101/lm.045369.117 |
| Citation | Lotfipour S, et al. (2017) alpha2* Nicotinic acetylcholine receptors influence hippocampus-dependent learning and memory in adolescent mice. Learn Mem 24(6):231-244 |
| abstractText | The absence of alpha2* 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 alpha2* nAChRs (Chrna2(L9'S/L9'S) and Chrna2(KO)) influence hippocampus-dependent learning and memory and CA1 synaptic plasticity. We substituted a serine for a leucine (L9'S) in the alpha2 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 Chrna2(L9'S/L9'S) male mice exhibited impaired learning and memory. The deficit was rescued by low-dose nicotine exposure. Electrophysiological studies demonstrated that hypersensitive alpha2 nAChRs potentiate acetylcholine-induced ion channel flux in oocytes and acute nicotine-induced facilitation of dorsal/intermediate CA1 hippocampal long-term potentiation in Chrna2(L9'S/L9'S) mice. Adolescent male mice null for the alpha2 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 alpha2* nAChRs influenced hippocampus-dependent learning and memory, as well as nicotine-facilitated CA1 hippocampal synaptic plasticity. |
