Neural circuit regulation of postnatal and adult subventricular zone neurogenesis: Mechanistic insights, functional models, and circuit-based neurological disorders

Neural circuits' role in regulating neurogenesis within the adult subventricular zone (SVZ) of the lateral ventricles (LV) has been extensively studied over the past two decades. The dynamic interplay between neurons, neurotransmitters, and LV neural stem cells (NSCs) highlights the critical influence of neural circuits on NSC renewal, proliferation, and differentiation. This article explores how neurotransmitters like dopamine, serotonin, GABA, acetylcholine, and glutamate regulate SVZ neurogenesis, revealing the cellular processes essential for NSC modulation and neuroblast generation. Recent studies have identified specific pathways, such as the ACC-subep-ChAT+ circuit, that modulate NSC activity and proliferation through muscarinic receptor activation and intracellular signaling cascades. These findings advance our understanding of the neural circuit basis of NSC regulation, with implications for brain development, neurological disorders, and circuit-based therapeutic strategies. Moreover, the current understanding emphasizes the importance of elucidating neural circuit interactions to fully grasp neurogenesis mechanisms and their relevance to neuronal repair, neurodevelopmental, and neurodegenerative disorders. Addressing the differences between human and rodent neurogenesis could enhance the translation of these insights into improved therapeutic strategies for neurodegenerative conditions. The article also discusses how single-cell multi-omics technologies are transforming the study of these processes, providing new insights into the molecular underpinnings of neurogenesis and neural circuit modulation in health and disease.