کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6271555 1614766 2015 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Overexpression of αCaMKII impairs behavioral flexibility and NMDAR-dependent long-term depression in the medial prefrontal cortex
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Overexpression of αCaMKII impairs behavioral flexibility and NMDAR-dependent long-term depression in the medial prefrontal cortex
چکیده انگلیسی


- Forebrain αCaMKII overexpression impairs behavioral flexibility.
- Forebrain αCaMKII overexpression selectively impairs NMDAR-dependent LTD in the mPFC.
- Forebrain αCaMKII overexpression impairs GluA1-Ser845 dephosphorylation and AMPAR internalization in the mPFC.

The medial prefrontal cortex (mPFC) participates in the behavioral flexibility. As a major downstream molecule in the NMDA receptor signaling, alpha-Ca2+/calmodulin-dependent protein kinase II (αCaMKII) is crucial for hippocampal long-term potentiation (LTP) and hippocampus-related memory. However, the role of αCaMKII in mPFC-related behavioral flexibility and mPFC synaptic plasticity remains elusive. In the present study, using chemical-genetic approaches to temporally up-regulate αCaMKII activity, we found that αCaMKII-F89G transgenic mice exhibited impaired behavioral flexibility in Y-water maze arm reversal task. Notably, in vitro electrophysiological analysis showed normal basal synaptic transmission, LTP and depotentiation, but selectively impaired NMDAR-dependent long-term depression (LTD) in the mPFC of αCaMKII-F89G transgenic mice. In accordance with the deficit in NMDAR-dependent LTD, αCaMKII-F89G transgenic mice exhibited impaired AMPAR internalization during NMDAR-dependent chemical LTD expression in the mPFC. Furthermore, the above deficits in behavioral flexibility, NMDAR-dependent LTD and AMPAR internalization could all be reversed by 1-naphthylmethyl (NM)-PP1, a specific inhibitor of exogenous αCaMKII-F89G activity. Taken together, our results for the first time indicate that αCaMKII overexpression in the forebrain impairs behavioral flexibility and NMDAR-dependent LTD in the mPFC, and supports the notion that there is a close relationship between NMDAR-dependent LTD and behavioral flexibility.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 310, 3 December 2015, Pages 528-540
نویسندگان
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