| First Author | Falk EN | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 10 | PubMed ID | 33674307 |
| Mgi Jnum | J:317319 | Mgi Id | MGI:6806833 |
| Doi | 10.1126/sciadv.abe1527 | Citation | Falk EN, et al. (2021) Nicotinic regulation of local and long-range input balance drives top-down attentional circuit maturation. Sci Adv 7(10) |
| abstractText | Cognitive function depends on frontal cortex development; however, the mechanisms driving this process are poorly understood. Here, we identify that dynamic regulation of the nicotinic cholinergic system is a key driver of attentional circuit maturation associated with top-down frontal neurons projecting to visual cortex. The top-down neurons receive robust cholinergic inputs, but their nicotinic tone decreases following adolescence by increasing expression of a nicotinic brake, Lynx1 Lynx1 shifts a balance between local and long-range inputs onto top-down frontal neurons following adolescence and promotes the establishment of attentional behavior in adulthood. This key maturational process is disrupted in a mouse model of fragile X syndrome but was rescued by a suppression of nicotinic tone through the introduction of Lynx1 in top-down projections. Nicotinic signaling may serve as a target to rebalance local/long-range balance and treat cognitive deficits in neurodevelopmental disorders. |
