Loss of α7 nicotinic acetylcholine receptors in GABAergic neurons causes sex-dependent decreases in radial glia-like cell quantity and impairments in cognitive and social behavior

The dentate gyrus (DG) is a unique brain structure in that neurons can be generated postnatally and integrated within existing circuitry throughout life. The maturation process of these newly generated neurons (granule cells) is modulated by nicotinic acetylcholine receptors (nAChRs) through a variety of mechanisms such as neural stem pool proliferation, cell survival, signal modulation, and dendritic integration. Disrupted nAChR signaling has been implicated in neuropsychiatric and neurodegenerative disorders, potentially via alterations in DG neurogenesis. GABAergic interneurons are known to express nAChRs, predominantly the alpha 7 subtype, and have been shown to shape development, integration, and circuit reorganization of DG granule cells. Therefore, we examined histological and behavioral effects of knocking out alpha 7 nAChRs in GABAergic neurons. Deletion of alpha 7 nAChRs resulted in a reduction of radial glia-like cells within the subgranular zone of the DG and a concomitant trend towards decreased immature neurons, specifically in male mice, as well as sex-dependent changes in several behaviors, including social recognition and spatial learning. Overall, these findings suggest alpha 7 nAChRs expressed in GABAergic neurons play an important role in regulating the adult neural stem cell pool and behavior in a sex-dependent manner. This provides important insight into the mechanisms by which cholinergic dysfunction contributes to the cognitive and behavioral changes associated with neurodevelopmental and neurodegenerative disorders.

Automated summary

The dentate gyrus is a unique brain structure where neurons can be generated postnatally and integrated into existing circuitry throughout life. Nicotinic acetylcholine receptors (nAChRs), particularly the alpha 7 subtype, play a crucial role in modulating the maturation process of newly generated neurons. Knocking out alpha 7 nAChRs in GABAergic neurons results in reduced radial glia-like cells, decreased immature neurons, and sex-dependent changes in behavior, including social recognition and spatial learning. These findings highlight the importance of alpha 7 nAChRs in regulating adult neural stem cell pool and behavior.