Khan, R. R. | Search bioRxiv

bioRxiv2022

Uncovering a neural circuit controlling adult quiescent neural stem cell activation in the subventricular zone

Neurogenesis and differentiation of the neural stem cells (NSCs) in the subventricular zone (SVZ) are controlled by cell-intrinsic molecular pathways that interact with extrinsic signaling cues. Here we identified a novel circuit that regulates neurogenesis and cellular proliferation in the lateral ventricle SVZ (LV-SVZ). Our results demonstrate direct glutamatergic inputs from the frontal cortex as well as local inhibitory interneurons, control the activity of distinctive cholinergic neurons in the subependymal zone (subep-ChAT+). In vivo optogenetic stimulation and inhibition in this circuit were sufficient to control local SVZ neurogenesis, LV NSCs proliferation, and SVZ cellular divisions in ventral SVZ. These findings shed light on local and distal neural circuit activity-dependent regulation of postnatal and adult SVZ neurogenesis and LV-SVZ cellular proliferation.

neuroscience↗

bioRxiv2020

Genetic variation in CSMD1 affects amygdala connectivity and prosocial behavior

The amygdala is one of the most widely connected structures in the primate brain and plays a key role in social and emotional behavior. Here, we present the first genome-wide association study (GWAS) of whole-brain resting-state amygdala networks to discern whether connectivity in these networks could serve as an endophenotype for social behavior. Leveraging published resting-state amygdala networks as a priori endophenotypes in a GWAS meta-analysis of two adolescent cohorts, we identified a common polymorphism on chr.8p23.2 (rs10105357 A/G, MAF (G)=0.35) associated with stronger connectivity in the medial amygdala network (beta=0.20, p=2.97x10-8). This network contains regions that support reward processes and affiliative behavior. People carrying two copies of the minor allele for rs10105357 participate in more prosocial behaviors (t=2.644, p=0.008) and have higher CSMD1 expression in the temporal cortex (t=3.281, p=0.002) than people with one or no copy of the allele. In post-mortem brains across the lifespan, we found that CSMD1 expression is relatively high in the amygdala (2.79 fold higher than white matter, p=1.80x10-29), particularly so for nuclei in the medial amygdala, reaching a maximum in later stages of development. Amygdala network endophenotyping has the potential to accelerate genetic discovery in disorders of social function, such as autism, in which CSMD1 may serve as a diagnostic and therapeutic target.

neuroscience↗