SPIN90 Modulates Long-Term Depression and Behavioral Flexibility in the Hippocampus
| Autor: | Sangmyung Rhee, Chong Hyun Kim, Yong Seok Lee, In Ha Cho, Chul-Seung Park, Woo Keun Song, Dae-Hwan Kim, Yun Hyun Huh, Minkyung Kang, Kyung Hwun Chung, Hyun Hee Ryu |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Dendritic spine Nonsynaptic plasticity AMPA receptor Biology lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine 90 kDa) SPIN90 (SH3 protein interacting with Nck Metaplasticity Long-term depression Molecular Biology lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Original Research behavioral flexibility synaptic plasticity Long-term potentiation long-term depression (LTD) 030104 developmental biology Synaptic fatigue Synaptic plasticity learning and memory Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Frontiers in Molecular Neuroscience Frontiers in Molecular Neuroscience, Vol 10 (2017) |
| ISSN: | 1662-5099 |
| Popis: | 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-GSK3β 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. |
| Databáze: | OpenAIRE |
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