| First Author | Letsinger AC | Year | 2023 |
| Journal | Front Neurosci | Volume | 17 |
| Pages | 1244118 | PubMed ID | 37746145 |
| Mgi Jnum | J:341192 | Mgi Id | MGI:7532091 |
| Doi | 10.3389/fnins.2023.1244118 | Citation | Letsinger AC, et al. (2023) Genetic deletion of alpha7 nAChRs reduces hippocampal granule and pyramidal cell number in both sexes but impairs pattern separation in males only. Front Neurosci 17:1244118 |
| abstractText | INTRODUCTION: Neurogenesis within the dentate gyrus is thought to play an important role in cognitive processes such as reversal learning and pattern separation. The alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) is expressed early in newly formed granule cells of the dentate gyrus, though its role in neurogenesis and related cognitive function is not fully understood. METHODS: To better characterize relevant function of alpha7 nAChRs, we performed unbiased stereology to quantify hippocampal granule cells, pyramidal cells, and total volume and used a touchscreen operant spatial discrimination/reversal task to test pattern separation in a global alpha7 nAChR knockout mouse line. RESULTS: The knockout resulted in an approximately 22% reduction in granule cells and a approximately 20% reduction in pyramidal cells in both sexes, with no change in total hippocampal volume. However, the knockout impaired performance in the touchscreen task for males only. The sex-dependent difference in behavioral, but not stereological, results suggest a divergence in the structure-function relationship in males versus females. Detailed analyses revealed males were more biased by the initial reversal contingency relative to females indicating a potential source of the sex-specific interaction with the loss of alpha7 nAChRs. DISCUSSION: These findings argue that the alpha7 nAChR plays a critical role in hippocampal development, not just granule cell neurogenesis, and plays a sex-dependent role in cognitive function. |
