The involvement of neuronal nitric oxide synthase (nNOS) in sound-inducedc-Fos expression in auditory processing in the inferior colliculus and auditory cortex of the rat
Description
My studies provided evidence for nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) function in the central auditory system. The auditory cortical and subcortical distributions of nNOS, sGC, PKG1alpha and PKG1beta proteins were examined, using histochemical and immunocytochemical methods of detection. Few auditory structures exhibited different expression patterns for nNOS and the other proteins. In the central nucleus of the inferior colliculus (CIC), the sGC and PKG1alpha antibodies had increased neuropil immunoreactivity which outlined the entire CIC, while nNOS antibody did not immunostain the neuropil. Other auditory structures, the nNOS immunostaining occurred in to interneurons. The sGC, PKG1alpha, and PKGbeta immunostaining occurred in both interneurons and projection neurons, indicating that interneurons might express all of the proteins. The results indicate two populations of neurons in the central auditory system exist. One population of neurons exhibited immunostaining for all the proteins of the NO/cGMP signaling cascade and other population expressed either nNOS or cGMP signaling cascade proteins. Since NO/cGMP signaling cascade proteins exhibited immunoreactivity in the subcortical and cortical auditory structures, these results signify the importance of NO/cGMP signaling cascade in acoustic processing Next the involvement of the NO/cGMP signaling cascade in sound induced c-Fos expression was determined by using the nNOS selective antagonist, 7-nitroindazole (7-NI). Three groups of rats were injected with vehicle, or with 7-NI or not injected. Half the rats in each group were exposed to sound stimulus for 40 minutes, while the others were not. In animals subjected to sound stimulation with or without vehicle pretreatment showed a significant increase of c-Fos immunoreactivity, compared to animals not exposed to sound with or without vehicle pretreatment. Pretreatment with 7-NI in the absence of sound induced a significant increase in c-Fos expression in DCN, IC, and Au, but not in occipital cortex, or entorhinal cortex. Pretreatment with 7-NI in the presence of sound significantly attenuated the c-Fos levels in DCN, IC, and Au. These data suggest a complex interaction between the effects of sound and nNOS in the central auditory pathway, and a decrease in nNOS activity may be a pathophysiological mechanism in hyperacusis, tinnitus and/or audiogenic seizures