| First Author | Su H | Year | 2022 |
| Journal | Neurobiol Learn Mem | Volume | 194 |
| Pages | 107674 | PubMed ID | 36029955 |
| Mgi Jnum | J:349820 | Mgi Id | MGI:7461326 |
| Doi | 10.1016/j.nlm.2022.107674 | Citation | Su H, et al. (2022) Nicotine-mediated activation of alpha2 nAChR-expressing OLM cells in developing mouse brains disrupts OLM cell-mediated control of LTP in adolescence. Neurobiol Learn Mem 194:107674 |
| abstractText | Early postnatal nicotine exposure, a rodent model of smoking during pregnancy, affects hippocampal synaptic plasticity and memory. Here, we investigated the role of alpha2 nAChR-expressing OLM (alpha2-OLM) cells in LTP in unexposed and postnatal nicotine-exposed mice. We found that reduced alpha2 nAChR-dependent activation of OLM cells in alpha2 heterozygous knockout mice prevented LTP, whereas enhanced alpha2 nAChR-dependent activation of OLM cells in heterozygous knockin mice expressing hypersensitive alpha2 nAChRs facilitated LTP. Both optogenetic and chemogenetic activation of alpha2-OLM cells facilitated LTP as nicotine did. However, in postnatal nicotine-exposed mice, expressing chemogenetic hM3Dq receptors in alpha2-OLM cells, LTP was facilitated and both nicotinic and chemogenetic activation of alpha2-OLM cells prevented rather than facilitated LTP. These results demonstrate a critical role of alpha2-OLM cell activation in LTP as well as altered alpha2-OLM cell function in postnatal nicotine-exposed mice. To determine whether nicotine-mediated alpha2 nAChR activation in developing brains causes facilitated LTP and altered nicotinic modulation of LTP in adolescence, we used homozygous knockin mice expressing hypersensitive alpha2 nAChRs as a way to selectively activate alpha2-OLM cells. In the knockin mice, postnatal exposure to a low dose of nicotine, which had no effect on LTP in wild-type mice, is sufficient to cause facilitated LTP and altered nicotinic modulation of LTP as found in wild-type mice exposed to a higher dose of nicotine. Thus, the nicotine-mediated activation of alpha2 nAChRs on OLM cells in developing brains disrupts the alpha2-OLM cell-mediated control of LTP in adolescence that might be linked to impaired memory. |
