Modulating the processing of complex sounds: How inhibition of nitric oxide alters evoked responses in the bullfrog torus semicircularis

Nitric Oxide (NO) is a gaseous molecule that functions as a retrograde messenger in several regions of the brain. Activation of glutamate N-methyl-D-aspartate (NMDA) receptors stimulates NO production via the activity of nitric oxide synthase (NOS). NO is released and subsequently enhances the presynaptic release of glutamate. Staining for β nicotinamide adenine dinucleotide phosphate diaphorase, an indicator of NO production, as well as immunohistochemical studies have revealed the presence of NOS-labeled neurons in a number of vertebrate brain structures including the inferior colliculus (IC), an important auditory processing center. These neurons presumably produce and release NO. However, the function of nitric oxide in auditory processing at the level of the IC is not known. Here we address this issue using extracellular single-unit recording combined with microiontophoresis to investigate the role of NO in how different species calls are analyzed by neurons in the IC of the American bullfrog, Lithobates catesbeiana. Of particular interest was if NO modulates the responses of IC neurons to conspecific and heterospecific mating calls. In vivo iontophoretic application of L-NAME (a NOS inhibitor), and L-Arg (a NOS substrate), was used to evaluate the effect of NO on the sound-evoked responses of neurons (n=35) in the IC. We found that NO modulated neuronal responses in a call dependent manner. Upon application of L-NAME we observed changes in neuronal responses with respect to spike counts, first-spike response latencies, and interspike intervals. Recovery of original response was seen after application of the NOS substrate, L-Arg after cessation of L-NAME application. Our data suggest a role for NO in regulating both gain control and response selectivity in the IC which may influence the output of neural circuits engaged in the analysis of behaviorally relevant acoustic signals, such as speech.