Nitric oxide signalling in the inferior colliculus

Abstract

This thesis investigates the distribution and function of neuronal nitric oxide synthase (nNOS) in the inferior colliculus (IC) the principal midbrain nucleus in the auditory pathway. Firstly, experiments using immunocytochemistry and fluorescent microscopy in the rat IC showed two, previously unreported, different subcellular distributions of nNOS in the IC. Secondly, the presence of nNOS positive post-synaptic puncta in the central nucleus suggests that nNOS, contrary to previous reports, is not limited to the IC cortices. Expression of nNOS was observed in both glutamatergic and GABAergic cells. Cells expressing nNOS were shown to often contain calbindin or parvalbumin but rarely calretinin. In vivo electrophysiological experiments were conducted in the anaesthetised guinea pig. Recording of multiunit neuronal activity was combined with local reverse microdialysis of drugs in the IC. Dialysis of NMDA increased both spontaneous and sound driven activity in the IC in a dose dependent manner. These effects were blocked when NMDA was paired with L-MeArg, a NOS inhibitor, or ODQ, a soluble guanylate cyclase (sGC) inhibitor. These results suggest that NMDA receptor-mediated effects in the IC involve NO and its action on sGC. Systemic administration of sodium salicylate, a drug known to induce tinnitus, resulted in a doubling of spontaneous activity in the IC. In contrast, local delivery of salicylate in the IC reduced spontaneous activity in a time/concentration-dependent manner. Both locally and systemically administered salicylate influenced sound driven activity, suggesting these effects are, in part, mediated directly within the IC. No effect of L-MeArg was observed on the salicylate mediated effects, but this could be due to methodological issues. These results demonstrate that NO play plays a role in sound processing in the IC and further work is required to establish its functional significance.