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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
- Source :
- Brain Struct Funct
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- 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 α7 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 α7 nAChRs in GABAergic neurons. Deletion of α7 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 α7 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.
- Subjects :
- Male
Doublecortin Protein
Histology
alpha7 Nicotinic Acetylcholine Receptor
Neurogenesis
Ependymoglial Cells
Spatial Learning
Cell Count
Biology
Article
050105 experimental psychology
Subgranular zone
Mice
03 medical and health sciences
Cognition
Sex Factors
0302 clinical medicine
medicine
Animals
0501 psychology and cognitive sciences
GABAergic Neurons
Social Behavior
Acetylcholine receptor
Mice, Knockout
Behavior, Animal
General Neuroscience
Dentate gyrus
05 social sciences
Neural stem cell
medicine.anatomical_structure
Nicotinic agonist
nervous system
Dentate Gyrus
GABAergic
Cholinergic
Female
Anatomy
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 18632661 and 18632653
- Volume :
- 226
- Database :
- OpenAIRE
- Journal :
- Brain Structure and Function
- Accession number :
- edsair.doi.dedup.....746050831c5178999c0be25a4f2482c7