Optical Approaches to Studying the Basal Ganglia

Altered synaptic integration is a major factor for many neurological disorders involving the basal ganglia, including Parkinson’s disease and Huntington’s disease. Despite the fact that most synaptic integration occurs within dendrites, nearly all we know about the physiology of basal ganglia neurons comes from somatic measurements. This is particularly true of neurons in the striatum, the major input nucleus of the basal ganglia. Principal spiny projection neurons (SPNs) of the striatum have fine caliber dendrites that are inaccessible using traditional patch-clamp electrodes. Two-photon laser scanning microscopy (2PLSM) and two-photon laser uncaging (2PLU) offer alternative strategies for studying synaptic integration in basal ganglia neurons, like SPNs. These methods also allow subcellular organelles like mitochondria to be monitored in physiologically meaningful settings. Combining these approaches with electrophysiological and optogenetic methodologies builds a powerful arsenal of investigational tools. This chapter describes how optical methodologies are being applied to the study of the basal ganglia.