of the research accomplishments of this project during the fiscal year, including its purpose or scope, research subjects, significant materials, and equipment or methods. The summary should be understandable to researchers not familiar with the specialty. Close Current research in our laboratory focuses on processing of auditory signals in the cochlear nucleus. Although much is known about how auditory information is represented by firing patterns of the auditory nerve, there are many outstanding questions about how these signals are processed in the brain. We have begun addressing questions about the function of the dorsal division of the cochlear nucleus (DCN). Principal neurons of the DCN, or fusiform cells, exhibit complex and nonlinear responses to sounds. In particular, they have been shown to respond to specific features of sounds known as spectral notches, which arise from the position-dependent acoustic filtering properties of the external ear. This feature has led to the hypothesis that one function of the DCN is to encode the location of sounds along the vertical axis. We are currently investigating the cellular and synaptic mechanisms underlying fusiform cell responses to sounds. Our experimental approach combines electrophysiology and cellular imaging to study synaptic transmission and plasticity in the cochlear nucleus. The main projects in the lab are summarized below. The first project addresses the role of endocannabinoids in modulating synaptic transmission at synapses formed by parallel fibers onto cartwheel cells, glycinergic interneurons that influence fusiform cell activity. Endocannabinoids act as retrograde messengers that are released from postsynaptic neurons and regulate synaptic strength over short and long time scales. Endocannabinoids regulate transmission at synapses in many brain region including auditory synapses but their role in auditory function is not known. We are currently investigating the mechanisms that regulate endocannabinoid release from cartwheel cells. Endocannabinoid release occurs by two distinct mechanisms. During periods of sustained action potential firing, endocannabinoids are released globally from cartwheel cell dendrites. Also, high-frequency activity of excitatory synaptic inputs can evoke localized release of endocannabinoids. Current experiments are focused on characterizing the cellular mechanisms responsible for this form of short-term synaptic plasticity and its influence on the output of the DCN. The goal of the second project is to develop techniques for in vivo recordings from individual neurons in the mouse DCN in response to sounds. We have developed the surgical techniques necessary for recording from the decerebrate mouse dorsal cochlear nucleus preparation and have collected preliminary data from putative DCN principal neurons. Our goal is to combine electrophysiological recording and anatomical labeling techniques to determine basic sound-driven response properties of DCN principal- and inter-neurons in the mouse preparation. Further experiments are planned to examine several aspects of cochlear nucleus function, including the hypothesis that endocannabinoids modulate synaptic transmission in the DCN and influence fusiform cell response properties. We have also initiated experiments to examine the role of cholinergic modulation in the DCN. Olivocochlear neurons in the brainstem provide cholinergic input to the cochlear nucleus but the function of this pathway is not known. Several classes of DCN neurons express muscarinic and nicotinic acetylcholine receptors. Our goals are to determine the effects of cholinergic receptor activation on synaptic transmission within the circuitry of the DCN. By determining the neurons targeted by acetylcholine in the DCN and the cellular mechanisms engaged by the activation of their cholinergic receptors, this work will contribute to our understanding of the role of cholinergic efferents in auditory function. These studies contribute to our understanding of how sensory stimuli are represented by neuronal activity and will enable improvements in our understanding and treatment of hearing disorders. Recent evidence implicates the DCN in tinnitus, a prevalent hearing disorder that impairs the quality of life of many people. Animal models of tinnitus demonstrate elevated activity levels in fusiform cells. However the mechanisms that produce this elevated activity are not known. A better understanding of the synaptic mechanisms responsible for the response properties of DCN neurons will enable us to test specific hypotheses about the alterations in the DCN that can cause tinnitus.
