Song, Sukwoon Kang, Miseon Lee, Jiyoung Yang, Yong Ryoul Lee, Ho Kim, Jae-Ick Kim, Beomsue Choi, Hoon-seong Hong, Eun-bin Nam, Min-ho Suh, Pann-Ghill Kim, Jeongyeon 2025-04-25T07:31:44Z 2025-04-25T07:31:44Z 2025-04-25 2025-04 1226-3613 https://pubs.kist.re.kr/handle/201004/152337 Phospholipase C (PLC) enzymes play crucial roles in intracellular calcium-signaling transduction. Several brain PLC subtypes have been extensively studied, implicating them in psychiatric disorders such as depression, epilepsy and schizophrenia. However, the role of the recently identified PLC eta remains largely unknown. We found that PLC eta 1 is prominently expressed in lateral habenula (LHb) astrocytes. Here, to investigate its physiological role, we generated astrocyte-specific PLC eta 1 conditional knockout (cKO) mice (Plch1f/f; Aldh1l1-CreERT2). In these cKO mice, we observed a reduction in cellular morphological complexity metrics, such as total process length, as well as a decrease in the passive membrane conductance of LHb astrocytes. Additionally, neuronal function was impacted by the cKO, as the synaptic efficacy and firing rates of LHb neurons increased, while extrasynaptic long-term depression was impaired. Both tonic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepdlropionic acid receptor/N-methyl-d-aspartate receptor (AMPAR/NMDAR) currents and extracellular glutamate levels were reduced. Interestingly, chemogenetic activation of astrocytes restored the reduced tonic AMPAR/NMDAR currents in cKO mice. Furthermore, LHb astrocyte-specific deletion of PLC eta 1 via AAV-GFAP-Cre injection induced depressive-like behaviors in mice, which were reversed by chemogenetic activation of LHb astrocytes. Finally, we found that restraint stress exposure decreased Plch1 mRNA expression in the LHb. These findings suggest that PLC eta 1 could be a potential therapeutic target for depression and highlight the critical role of astrocytes in the etiology of neuropsychiatric disorders. English Springer Nature Role of phospholipase Cη1 in lateral habenula astrocytes in depressive-like behavior in mice Article 10.1038/s12276-025-01432-1 1 Experimental & Molecular Medicine, v.57, no.4, pp.872 - 887 Experimental & Molecular Medicine 57 4 872 887 Y scie scopus kci 001462512700001 2-s2.0-105002184464 Biochemistry & Molecular Biology Medicine, Research & Experimental Biochemistry & Molecular Biology Research & Experimental Medicine Article C-ETA ENZYMES MOLECULAR-CLONING GLUTAMATE RELEASE POTASSIUM MOUSE ACTIVATION EXPRESSION CHANNELS CURRENTS CALCIUM