Neuromodulation in the auditory system

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Project Summary Understanding speech depends on the capacity of the auditory system to accurately represent salient sounds. This representation may be altered by a variety of factors, including disorders involving neuromodulatory systems. For example, patients with Parkinson's disease have speech processing problems suggesting that dopamine alters normal representation of these salient signals. The proposed studies focus on the role of dopamine in altering representation of salient sounds in the inferior colliculus (IC). The IC is a prime location for modulating auditory processing of salient signals because it receives input from multiple auditory and non-auditory source, it contains dopamine receptors and fibers, and preliminary data from this proposal indicate that dopamine modulates IC auditory responses. The objective of this proposal is to determine the mechanisms by which dopamine alters the representation of vocalizations in IC. The first Aim will use in vivo single unit recordings with application of pharmacological agents in the IC of awake mice to determine the effects of dopamine receptor activation on responses to vocalizations. The second Aim will use whole-cell recordings in mouse IC brain slices to determine the effects of dopamine on intrinsic and synaptic properties of different neuron types. The third Aim will use in vivo whole-cell recordings to identify how intrinsic properties of different neuron types shape selectivity to vocalizations. Aims 1-3 will thus provide an integrated understanding of the cellular and synaptic mechanisms underlying auditory responses to complex sounds. The fourth Aim will determine the sources of dopaminergic input to the IC, an important step towards understanding the behavioral contexts that elicit dopamine release into the IC. The significance of this proposal is that it is the first integrated study of the effects of dopamine on the cellular, synaptic and circuit properties underlying IC responses to salient sounds. The results will increase our mechanistic understanding of auditory processing of meaningful sounds and how this encoding changes with different social contexts, physiological states and communication disorders. These studies using mice with normal hearing will facilitate future studies of genetically engineered mice to further probe the mechanisms underlying specific communication and neurological disorders.