Group 1 mGIuR-Dependent Synaptic Long-Term Depression: Mechanisms and Implications for Circuitry and Disease

Many excitatory synapses express Group 1, or Gq coupled, metabotropic glutamate receptors (Gp1 mGIuRs) at the periphery. of their postsynaptic density. Activation of Gpl mGIuRs typically occurs in response to strong activity and triggers long-term plasticity of synaptic transmission in many brain regions, including the neocortex, hippocampus, midbrain, striatum, and cerebellum. Here we focus on mGIuR-induced long-term synaptic depression (LTD) and review the literature that implicates Gpl mGIuRs in the plasticity of behavior, learning, and memory. Moreover, recent studies investigating the molecular mechanisms of mGIuR-LTD have discovered links to mental retardation, autism, Alzheimer's disease, Parkinson's disease, and drug addiction. We discuss how mGIuRs lead to plasticity of neural circuits and how the understanding of the molecular mechanisms of mGIuR plasticity provides insight into brain disease.