The dorsal cochlear nucleus (DCN) is part of the brainstem complex that serves as the first processing station for auditory input within the brain. Although its function is not completely understood, an integration of information from auditory and non-auditory sources within the DCN may play a role in extracting auditory information as it relates to the overall sensory environment. The objective of this study is to examine the mechanisms that underlie the complex responses of cartwheel cells (CWCs), a population of interneurons within the superficial DCN that respond to non-auditory stimuli and inhibit the auditory responses of pyramidal cells (PCs) that project to the inferior colliculus. Unlike many neurons, which respond to excitatory inputs with single or repetitive action potentials known as simple spikes, CWCs can respond to excitation with a rapid burst of action potentials known as complex spikes. CWCs are also capable of generating simple spikes and it is not clear what determines their response to excitatory stimuli. Because of their role in shaping information projected from the DCN to higher auditory centers within the brain, it is important to understand what conditions determine the responses of CWCs. The proposed experiments employ whole-cell voltage-clamp recordings, fluorescence imaging of calcium influx, focal application of pharmacologic agents, and computational modeling to examine the contribution of voltage-gated calcium and potassium channels to the generation of complex spikes in CWCs in a brainstem slice preparation.
The first aim of this application is to investigate the properties and distribution of calcium channels that underlie complex spikes, and to test the hypothesis that low-threshold, non-inactivating calcium channels in the soma and proximal dendrites are responsible for complex spike generation in CWCs.
The second aim i s to examine how potassium channels regulate complex spiking in CWCs and to test the hypothesis that calcium-activated potassium channels regulate CWC discharge patterns by attenuating the slow calcium-dependent depolarization underlying complex spikes. The focus of the third aim is to examine conditions that determine CWC discharge patterns and to investigate the hypothesis that simple spikes are preferentially evoked over complex spikes under conditions that elevate cytosolic free calcium levels. These experiments should provide valuable information about the generation of electrophysiologic responses in CWCs and provide greater understanding about the role of CWCs in modulating DCN output.
