Dendritic integration and synaptic plasticity in the MSO

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DESCRIPTION (provided by applicant): Time-varying features of sound are critical cues that humans and other mammals use to not only understand speech and other communication signals, but to localize sounds as well. The long-term goal of this research is to understand the factors that shape the physiology and development of the auditory circuits underlying these functions. This information is critical not only for understanding the neurobiological basis of human hearing, but also for the development of behavioral strategies that address communication disorders of the central nervous system. This proposal focuses on the medial superior olive (MSO), a major ascending auditory pathway in the brainstem that conveys information about the temporal structure and location of low-frequency sounds. The projecting neurons of the MSO detect the sub millisecond temporal disparities in the arrival of sounds to the two ears, and transmit these cues to higher auditory centers. Within each MSO neuron, the decision whether or not to signal depends on the integration of synaptic inputs in the dendrites, the narrow, branched structures that receive the majority of synaptic input. Despite the pivotal position of the dendrites in processing binaural information, their function remains uninvestigated, due to the technical difficulty of recording electrical activity directly from these small structures. The present study will combine dendritic patch-clamp recordings with calcium imaging in brain slices to examine for the first time dendritic integration in a central auditory neuron. First, experiments will test the hypothesis that voltage-gated channels shape the responses of MSO principal neurons to sub threshold synaptic activity as well as the initiation and propagation of action potentials. Second, we will explore the hypothesis that the strength of synaptic connections to MSO neurons is plastic during development, and regulated by the intrinsic ion channels in the neuron. Finally, experiments will pursue the hypothesis that intracellular calcium influx is the cellular mechanism that links the activity of intrinsic voltage- and ligandgated channels with subsequent changes in synaptic strength. These changes in synaptic strength likely underlie the formation of behaviorally appropriate connections during development, and might represent a form of auditory learning at a low level of the central auditory system.