Electrophysiological and Calcium Imaging Approaches to Study Metabotropic Glutamate Receptors

Abstract

The activation of metabotropic glutamate receptors (mGluRs) has a strong impact on neuronal action potential generation, membrane potential, and input resistance. Activation of mGluR, however, does not directly cause charge movement across the plasma membrane, and thus cannot be directly measured in an electrophysiological recording. Instead, mGluR activation can affect numerous downstream targets, many of which are ion channels that can be studied using electrophysiological and/or Ca2+ imaging techniques. Hence, electrophysiological research on mGluR-mediated effects has become a well-established field. This chapter will give examples of methods used to investigate the cellular electrophysiology and downstream mechanisms of mGluR activation. First, examples of downstream signaling targets that can be identified using electrophysiological techniques or a combination of Ca2+-imaging and electrophysiology are given. Second, the importance of Ca2+ ions in such downstream signaling is explained. Lastly, the use of voltage ramps in analyzing mGluR downstream effects is emphasized. These techniques have proven beneficial for understanding the role of mGluRs in many physiological and pathophysiological contexts, such as oscillatory thalamocortical and hippocampal activity, electrical and chemical synaptic plasticity, neurodegenerative diseases, epileptogenesis, alcohol dependence, and anxiety.