NEE Seminar Series

2025-05-29      강미선 박사님 (한국뇌연구원(KBRI) 정서인지질환 연구그룹)

시간: 2025년 5월 29일(목) 14:00 장소: 이화여대 아산공학관 521호

제목: Role of phospholipase Cη1 in lateral habenula astrocytes in depressive-like behavior in mice

초록: Phospholipase C (PLC) enzymes are key regulators of intracellular calcium signaling and have been implicated in various psychiatric disorders, including depression, epilepsy, and schizophrenia. While several PLC subtypes have been extensively studied, the physiological role of the recently identified PLCη family remains unclear. Here, we identify prominent expression of PLCη1 in astrocytes of the lateral habenula (LHb), a brain region critically involved in mood regulation. To investigate its function, we generated astrocyte-specific PLCη1 conditional knockout (cKO) mice (Plch1f/f;Aldh1l1-CreERT2). In these cKO mice, LHb astrocytes exhibited reduced morphological complexity. These astrocytic alterations were accompanied by increased synaptic efficacy and elevated firing rates of LHb neurons, as well as impaired extra-synaptic long-term depression (LTD). Additionally, tonic AMPA and NMDA receptor-mediated currents and extracellular glutamate levels were significantly reduced. Remarkably, chemogenetic activation of LHb astrocytes rescued the diminished tonic AMPAR/NMDAR currents in cKO mice. Behaviorally, LHb-targeted deletion of PLCη1 using AAV-GFAP-Cre induced depressive-like behaviors, which were reversed by astrocyte-specific chemogenetic activation. Finally, exposure to restraint stress led to a downregulation of Plch1 mRNA in the LHb.Together, these findings uncover a critical role for astrocytic PLCη1 in maintaining LHb circuit function and emotional behavior, suggesting that PLCη1 is a promising target for therapeutic intervention in depression and related neuropsychiatric disorders.