Metabotropic glutamate receptors and cognition: From underlying plasticity and neuroprotection to cognitive disorders and therapeutic targets.

Abstract

Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors that play pivotal roles in mediating the activity of neurons and other cell types within the brain, communication between cell types, synaptic plasticity, and gene expression. As such, these receptors play an important role in a number of cognitive processes. In this chapter, we discuss the role of mGlu receptors in various forms of cognition and their underlying physiology, with an emphasis on cognitive dysfunction. Specifically, we highlight evidence that links mGlu physiology to cognitive dysfunction across brain disorders including Parkinson's disease, Alzheimer's disease, Fragile X syndrome, post-traumatic stress disorder, and schizophrenia. We also provide recent evidence demonstrating that mGlu receptors may elicit neuroprotective effects in particular disease states. Lastly, we discuss how mGlu receptors can be targeted utilizing positive and negative allosteric modulators as well as subtype specific agonists and antagonist to restore cognitive function across these disorders.