| First Author | Venkatesan S | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 2 | Pages | 105992 |
| PubMed ID | 36798433 | Mgi Jnum | J:337522 |
| Mgi Id | MGI:7437068 | Doi | 10.1016/j.isci.2023.105992 |
| Citation | Venkatesan S, et al. (2023) Chrna5 and lynx prototoxins identify acetylcholine super-responder subplate neurons. iScience 26(2):105992 |
| abstractText | Attention depends on cholinergic excitation of prefrontal neurons but is sensitive to perturbation of alpha5-containing nicotinic receptors encoded by Chrna5. However, Chrna5-expressing (Chrna5+) neurons remain enigmatic, despite their potential as a target to improve attention. Here, we generate complex transgenic mice to probe Chrna5+ neurons and their sensitivity to endogenous acetylcholine. Through opto-physiological experiments, we discover that Chrna5+ neurons contain a distinct population of acetylcholine super-responders. Leveraging single-cell transcriptomics, we discover molecular markers conferring subplate identity on this subset. We determine that Chrna5+ super-responders express a unique complement of GPI-anchored lynx prototoxin genes (Lypd1, Ly6g6e, and Lypd6b), predicting distinct nicotinic receptor regulation. To manipulate lynx regulation of endogenous nicotinic responses, we developed a pharmacological strategy guided by transcriptomic predictions. Overall, we reveal Chrna5-Cre mice as a transgenic tool to target the diversity of subplate neurons in adulthood, yielding new molecular strategies to manipulate their cholinergic activation relevant to attention disorders. |
