Sutley-Koury, Samantha N.Taitano-Johnson, ChristopherKulinich, Anna O.Farooq, NadiaWagner, Victoria A.Robles, MarissaHickmott, Peter W.Santhakumar, VijayalakshmiMimche, Patrice N.Ethell, Iryna M.2024-12-062024-12-062024-11-06Sutley-Koury SN, Taitano-Johnson C, Kulinich AO, et al. EphB2 Signaling Is Implicated in Astrocyte-Mediated Parvalbumin Inhibitory Synapse Development. J Neurosci. 2024;44(45):e0154242024. Published 2024 Nov 6. doi:10.1523/JNEUROSCI.0154-24.2024https://hdl.handle.net/1805/44787Impaired inhibitory synapse development is suggested to drive neuronal hyperactivity in autism spectrum disorders (ASD) and epilepsy. We propose a novel mechanism by which astrocytes control the development of parvalbumin (PV)-specific inhibitory synapses in the hippocampus, implicating ephrin-B/EphB signaling. Here, we utilize genetic approaches to assess functional and structural connectivity between PV and pyramidal cells (PCs) through whole-cell patch-clamp electrophysiology, optogenetics, immunohistochemical analysis, and behaviors in male and female mice. While inhibitory synapse development is adversely affected by PV-specific expression of EphB2, a strong candidate ASD risk gene, astrocytic ephrin-B1 facilitates PV→PC connectivity through a mechanism involving EphB signaling in PV boutons. In contrast, the loss of astrocytic ephrin-B1 reduces PV→PC connectivity and inhibition, resulting in increased seizure susceptibility and an ASD-like phenotype. Our findings underscore the crucial role of astrocytes in regulating inhibitory circuit development and discover a new role of EphB2 receptors in PV-specific inhibitory synapse development.en-USAttribution 4.0 InternationalAstrocyteEphB receptorHippocampusInhibitionParvalbuminSynapseArticle