Chapter 11 - Nitric Oxide Signaling in the Striatum

Abstract

Striatal medium-sized spiny neurons contain high levels of soluble guanylyl cyclase (sGC), 3′-5′-cyclic guanosine monophosphate (cGMP)-dependent protein kinase and other components of the cGMP signaling system. Striatal sGC-cGMP signaling is activated by the gaseous neuromodulator nitric oxide (NO). A growing body of literature indicates that under physiological conditions, NO-producing interneurons are potently activated by glutamate and dopamine (DA). The complex nature of the modulatory effects of NO on striatal neurons likely depends on the effector pathways recruited during NO signaling and the relative activity and subtype of neurons under study. Indeed, a review of electrophysiological studies indicates that NO exerts a variety of effects on local circuit neurons and projection neurons involved in regulating basal ganglia output and motor behavior. In addition to summarizing these influences, this chapter discusses the impact of striatal DA depletion on NO signaling and examines the relevance of nitrergic dysregulation for the pathophysiology of Parkinson's disease.