Lateral Ventricular Neural Stem Cells Provide Negative Feedback to Circuit Activation Through GABAergic Signaling

Recent studies have demonstrated that circuit activation in vivo can regulate proliferation of lateral ventricular neural stem cells (LV NSCs), although the underlying molecular and cellular mechanisms are not yet fully understood. Here, we investigated the role of GABAergic signaling in the interaction between LV NSCs and the anterior cingulate cortex-subependymal-choline acetyltransferase⁺ (ChAT⁺) neuron (ACC-subep-ChAT⁺) circuit. We found that monoamine oxidase B (MAOB), a key enzyme involved in gamma-aminobutyric acid (GABA) synthesis, is expressed in LV NSCs, and that activation of the ACC-subep-ChAT⁺ circuit can modulate MAOB activity. Additionally, LV NSCs express LRRC8D, a core component of volume-regulated anion channels, and GABA transporter-1 (GAT-1, SLC6A1). We show evidence that, through GABA signaling, LRRC8D and GAT-1 can provide a negative feedback signal to ChAT⁺ neurons, a key component of the ACC-subep-ChAT⁺ circuit that regulate proliferation of LV NSCs. These findings suggest that MAOB-driven GABA synthesis, LRRC8D-regulated chloride and GABA transport, and GAT-1-facilitated GABA reuptake can regulate neural circuit activation and influence NSC proliferation dynamics in the LV.