Dopaminergic Modulation of Corticostriatal Interactions and Implications for Parkinson’s Disease

Abstract

The striatum includes the structures of the caudate, putamen, and nucleus accumbens (Nacb) and is a subset of the subcortical interconnected nuclei that make up the basal ganglia [39]. The striatum is one of the major input structures of the basal ganglia and integrates input from many cortical areas as well as the thalamus. In general, the dorsal striatum processes more input from the motor regions of the cortex, while the ventral striatum processes input predominantly from the limbic and cognitive areas of the brain [2]. The predominant cell in the striatum is the GABAergic medium spiny neuron (MSN), comprising over 95% of the striatal cells in the rodent [39]. The other 3 5% of cells in the striatum are GABAergic and cholinergic interneurons, each of which plays an important role in striatal function [38]. While each MSP cell has a small soma (10–15 mM), it has a large dendritic structure (200–300 mM) with numerous spines, and a branching axonal segment. The branching axonal arbor can be larger than the dendritic arbor, makes lateral contacts with other MSNs, and has one portion of the axonal segment projecting to efferent structures. The processing of afferent input by these MSNs has been the focus of numerous investigations, as has the role of dopaminergic (DA) modulation in affecting the integration of both inputs and the output of the MSNs [6, 32, 27, 31]. MSNs have a bimodal membrane potential under anesthesia or in vitro (see below), and one of the critical questions about their processing of cortical input has been whether they can maintain their depolarized state via intrinsic mechanisms without any further synaptic input. We have addressed some of the issues associated with cortical input to the striatal MSNs by examining how much synaptic input is required to keep the cell in the depolarized state, as well as comparing the structure of the cortical input