| First Author | Ma J | Year | 2015 |
| Journal | Neuroscience | Volume | 310 |
| Pages | 528-40 | PubMed ID | 26415772 |
| Mgi Jnum | J:227489 | Mgi Id | MGI:5700588 |
| Doi | 10.1016/j.neuroscience.2015.09.051 | Citation | Ma J, et al. (2015) Overexpression of alphaCaMKII impairs behavioral flexibility and NMDAR-dependent long-term depression in the medial prefrontal cortex. Neuroscience 310:528-40 |
| abstractText | The medial prefrontal cortex (mPFC) participates in the behavioral flexibility. As a major downstream molecule in the NMDA receptor signaling, alpha-Ca(2+)/calmodulin-dependent protein kinase II (alphaCaMKII) is crucial for hippocampal long-term potentiation (LTP) and hippocampus-related memory. However, the role of alphaCaMKII in mPFC-related behavioral flexibility and mPFC synaptic plasticity remains elusive. In the present study, using chemical-genetic approaches to temporally up-regulate alphaCaMKII activity, we found that alphaCaMKII-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 alphaCaMKII-F89G transgenic mice. In accordance with the deficit in NMDAR-dependent LTD, alphaCaMKII-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 alphaCaMKII-F89G activity. Taken together, our results for the first time indicate that alphaCaMKII 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. |
