Kim, Dae Hwan Kang, Minkyung Kim, Chong-Hyun Huh, Yun Hyun Cho, In Ha Ryu, Hyun-Hee Chung, Kyung Hwun Park, Chul-Seung Rhee, Sangmyung Lee, Yong-Seok Song, Woo Keun 2024-01-20T00:32:32Z 2024-01-20T00:32:32Z 2021-09-05 2017-09-20 1662-5099 https://pubs.kist.re.kr/handle/201004/122271 The importance of actin-binding proteins (ABPs) in the regulation of synapse morphology and plasticity has been well established. SH3 protein interacting with Nck, 90 kDa (SPIN90), an Nck-interacting protein highly expressed in synapses, is essential for actin remodeling and dendritic spine morphology. Synaptic targeting of SPIN90 to spine heads or dendritic shafts depends on its phosphorylation state, leading to blockage of cofilin-mediated actin depolymerization and spine shrinkage. However, the physiological role of SPIN90 in long-term plasticity, learning and memory are largely unknown. In this study, we demonstrate that Spin90-knockout (KO) mice exhibit substantial deficits in synaptic plasticity and behavioral flexibility. We found that loss of SPIN90 disrupted dendritic spine density in CA1 neurons of the hippocampus and significantly impaired long-term depression (LTD), leaving basal synaptic transmission and long-term potentiation (LTP) intact. These impairments were due in part to deficits in AMPA receptor endocytosis and its pre-requisites, GluA1 dephosphorylation and postsynaptic density (PSD) 95 phosphorylation, but also by an intrinsic activation of Akt-GSK3 beta signaling as a result of Spin90-KO. In accordance with these defects, mice lacking SPIN90 were found to carry significant deficits in object-recognition and behavioral flexibility, while learning ability was largely unaffected. Collectively, these findings demonstrate a novel modulatory role for SPIN90 in hippocampal LTD and behavioral flexibility. English FRONTIERS MEDIA SA SYNAPTIC PLASTICITY DENDRITIC SPINES NMDA RECEPTOR STRUCTURAL PLASTICITY ACTIN CYTOSKELETON SIGNALING PATHWAYS MEMORY DEFICITS KNOCKOUT MICE PHOSPHORYLATION MECHANISMS SPIN90 Modulates Long-Term Depression and Behavioral Flexibility in the Hippocampus Article 10.3389/fnmol.2017.00295 1 FRONTIERS IN MOLECULAR NEUROSCIENCE, v.10 FRONTIERS IN MOLECULAR NEUROSCIENCE 10 scie scopus 000411184300001 2-s2.0-85032273990 Neurosciences Neurosciences & Neurology Article SYNAPTIC PLASTICITY DENDRITIC SPINES NMDA RECEPTOR STRUCTURAL PLASTICITY ACTIN CYTOSKELETON SIGNALING PATHWAYS MEMORY DEFICITS KNOCKOUT MICE PHOSPHORYLATION MECHANISMS SPIN90 (SH3 protein interacting with Nck 90 kDa) long-term depression (LTD) behavioral flexibility synaptic plasticity learning and memory