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mGluR5 Expression Is Required for NMDA-Receptor Dependent Forms of Plasticity in Mouse Visual Cortex
Objectives: We sought to understand how mGluR5 regulates experience-dependent synaptic plasticity in mouse visual cortex. This is critically important because mGluR5 antagonists are currently in clinical trials for FX.
Methods: We measured synaptic plasticity in vitro using both whole-cell and field potential recordings, and in vivo in an awake, head-fixed setup where the animal views visual stimuli.
Results: Surprisingly, we found that mGluR5 is required for long-term depression (LTD) in slice and forms of experience-dependent plasticity in vivo. Additionally, chronic administration of the mGluR5 antagonist CTEP results in similar phenotypes seen in the mGluR5 knockout mouse.
Conclusions: This work suggests that signaling through mGluR5 during development is crucial to establish forms of NMDA receptor-dependent plasticity in adulthood. In the context of Fragile X, this work suggests that the timing and location of mGluR5-mediated pharmacological therapies are crucial.