Chapter 6 - Nitric Oxide and Excitatory Amino Acid-Coupled Signal Transduction in the Cerebellum and Hippocampus

Abstract

This chapter discusses nitric oxide (NO) and excitatory amino acid (EAA)-coupled signal transduction in the cerebellum and hippocampus. NO has a short half-life; this diffusible intra- and intercellular messenger molecule possesses tremendous potential to modulate neurotransmission. Within the cerebellum, all three major ionotropic EAA receptor populations are present and activation of each subtype results in increased cerebellar cyclic GMP (cGMP) levels, each with its own demonstrated pharmacological specificity. The basal tone of EAA transmission in the cerebellum can be augmented by pharmacological activation of the N-methyl-D-aspartate (NMDA)-associated glycine receptor, and argues against the saturation of this receptor site by endogenous glycine. In the granular layer, the GABAergic interneurons lack nNOS, while the EAA-utilizing neurons, the granule cells and their afferent inputs, the mossy fibers, possess high levels of neuronal nitric oxide synthase (nNOS). Action-dependent formation of NO in cerebellar slices has been demonstrated to induce dramatic increases in NO and cGMP generation, with these actions being dependent on intact climbing fiber inputs. EAA-induced neuronal losses are independent of NO and cGMP.