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Calcium Signaling Pathways Involved in Long-Term Potentiation at Excitatory Synapses on Parvalbumin Positive Fast-Spiking GABAergic Neurons in the Mouse Visual Cortex

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Objective: Recently, we reported the presence of metabotropic glutamate receptor type 5 (mGluR-5) dependent long-term potentiation (LTP) at excitatory synapses on fast-spiking GABAergic (FS-GABA) cells in the visual cortex. In this study, we report a Ca2+ signaling pathway involved in this LTP type. Materials and Methods: Brain slices from GAD67-GFP knock-in mice were used. Using whole-cell patch-clamp recording followed by immunohistochemical staining on parvalbumin- positive (PV+) FS-GABA cells, we studied the Ca2+ signaling pathway involved in excitatory LTP of certain visual cortical interneuron subtypes. Results: U-73122- a phospolipas c (PLC) inhibitor (10 ىM), inositol triphosphate (IP3) inhibitors such as 2-APB (3 ىM) and heparin (10 IU/ml), and CPA- the internally stored Ca2+ release inhibitor- (5 ىM) blocked the mGluR5 signaling pathway to induce LTP at excitatory synapses on PV+ fast-spiking cells in the visual cortex. However, application of the vehicles alone had no effect. Conclusion: Our results indicate that mGluR-5 at FS-GABA neurons activate PLC and IP3 production. This leads to Ca2+ release, promotes LTP induction, and its maintenance is supported by internal Ca2+ stores. Considering the key role of PV+ FS inhibitory neurons in the visual cortex circuits, we suggest that the metabotropic glutamate receptor-dependent LTP of excitatory synapses to FS cells plays a crucial role in the visual cortex plasticity.

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