Regulation of excitability in a sensory system by cellular and network components

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DESCRIPTION (provided by applicant): A principal task of the auditory system is to process the temporal and intensity information contained in a sound stimulus, which it does by integrating excitatory and inhibitory input from different sources. The first nucleus in the central nervous system, where such integration occurs, is the inferior colliculus (IC). The IC is a brainstem nucleus. It receives direct input from most of the auditory nuclei in the brainstem and, in turn, provides nearly all of the input to the auditory forebrain. In addition to its importance in auditory processing, the IC is the site of origin of pathological hyperexcitability that leads to sound-evoked seizures. Despite its strategic location and extensive input convergence, the regulation of excitability by inputs and intrinsic neuronal properties has not been investigated, and the definition of a basic circuit in terms of defined classes of cells and connections is necessary to understand its function. We recently demonstrated that excitatory and inhibitory inputs to the IC selectively regulate gain control and neuronal excitability. This regulation of gain control determines how well neurons in the IC can code sound intensity. We have also found evidence for local excitatory recurrent circuits in the IC. Furthermore, activity is propagated in a complex fashion between the two sides of IC. We will combine electrophysiological recordings of activity in single neurons, optical monitoring of neuronal population responses with voltage-sensitve dyes and computational modeling techniques to address the following specific aims: 1. Determine how patterned synaptic input regulates the excitatory/inhibitory ratio in single IC neurons. 2. Determine the importance of cell type specificity in local and inter-collicular circuitry. 3. Determine the requirements for inter-collicular connectivity. Our results will delineate the constraints on excitability in the normal auditory system set by network and cellular components, and will further our understanding of the factors that lead to the hyperexcitable state that gives rise to epileptic seizures.