DESCRIPTION (provided by applicant): We study the mechanisms by which neurons encode sound location, using the chick auditory brain stem as a model system. This research has broad relevance to understanding how brain circuits extract behaviorally relevant information from sensory input. The project may also advance the long-term, health-related goal of developing cochlear implants that more effectively drive the brain circuits responsible for normal hearing. The proposed studies will investigate the neurons in Nucleus Laminaris (NL), which is the first site in the chicken's auditory pathway that receives signals from both ears and can detect the location of a sound source. Neurons in different parts of NL respond to different sound frequencies (called characteristic frequency, or CF). Previous studies have shown that neurons with different CF have different properties, and we believe that these differences tune the neurons to respond best to signals of a particular frequency. The input signals that excite NL neurons, known as excitatory postsynaptic currents (EPSCs), show large differences between NL neurons of different CF. Specifically, EPSCs in low-CF neurons are smaller and slower than those in high-CF cells. We believe that these differences are important for tuning NL neurons to different frequencies. The mechanisms underlying the differences in EPSCs are not known, but previous morphological studies of NL neurons suggest an interesting hypothesis. These studies showed that the dendrites of NL neurons, which are the structures that receive EPSCs, are much longer on low-CF cells than on high-CF cells. After arriving at a neuron, the EPSC must travel down the dendrite to the cell body in order to trigger an output response (the action potential). In other neurons, it is known that long dendrites reduce the size of the EPSC and slow it down by the time it reaches the cell body. This process is called dendritic filtering. We hypothesize that EPSCs in low-CF NL neurons are slower than those in high-CF cells because of dendritic filtering. We propose two specific aims to test this hypothesis. For both, we will record electrically from NL neurons in slices of the chick brainstem. In the first aim, we will elicit EPSCs by electrical stimulation of incoming nerve fibers. The amount of dendritic filtering will be measured based on the changes in the EPSC caused by changing the voltage of the cell body at different times. If the amount of dendritic filtering is large, we will have to change the voltage well before the EPSC in order to see an effect. In the second aim, we will use a different stimulus (concentrated sucrose) to elicit EPSCs on specific parts of the cell. If there is much dendritic filtering, EPSCs from the dendrites will be smaller and slower than those elicited at the cell body. Beyond its scientific value, this research will provide training in patch clamp recording, morphological studies of the recorded neurons, and computer programming and software applications for data acquisition and analysis. It is hoped that studies in this beautifully organized, well-characterized neural system will also encourage intellectual development, leading to proficiency as an independent investigator in the field. PUBLIC HEALTH RELEVANCE: While the proposed research is basic in nature, it may eventually contribute to public health by providing a more rational foundation for the design of cochlear implants. At present, cochlear implants are of great benefit to many patients with hearing loss but fall far short of restoring normal hearing, particularly for complex stimuli such as speech and music. A greater understanding of the response properties of neurons in brainstem auditory circuits may aid in the design of implants that produce output signals tailored to the properties of recipient neurons, allowing greater transmission of relevant sound information.

Narrative While the proposed research is basic in nature, it may eventually contribute to public health by providing a more rational foundation for the design of cochlear implants. At present, cochlear implants are of great benefit to many patients with hearing loss but fall far short of restoring normal hearing, particularly for complex stimuli such as speech and music. A greater understanding of the response properties of neurons in brainstem auditory circuits may aid in the design of implants that produce output signals tailored to the properties of recipient neurons, allowing greater transmission of relevant sound information.