MECHANISMS OF PERSISTENT NEURAL ACTIVITY

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The long-range goal of this research is to identify the cellular and circuit mechanisms responsible for maintaining persistent neural activity: a sustained change in sodium action potential firing related to short-term memory that has been observed in many brain areas. Our program combines experimental and theoretical studies of the oculomotor integrator, where persistent neural activity is related to a short-term memory of the current eye position. The experimental preparation is the goldfish, which, is particularly advantageous for a cellular and computational analysis of mechanisms. Our specific aims are to test the following hypotheses: 1. Storage of the memory of eye position is completely localized in hindbrain Area I. 2. Cellular mechanisms maintain persistent neural activity. 3. Circuit mechanisms maintain persistent neural activity. 4. The variability and synchrony of persistent neural activity reflects network interactions. Methods Persistent neural activity in awake goldfish will be measured and perturbed by intracellular recording to test hypothetical cellular mechanisms of persistent neural activity. The intrinsic and synaptic conductances of integrator neurons will be studied in vitro, and a numerical model will be constructed from the results. Synaptic connectivity will be determined by intracellular fills in vivo and dual recording in vitro, and incorporated into a network of conductance-based model neurons. The effects of pharmacological agents on behavior and neural activity will be compared with model predictions. The properties of correlated neural activity will be measured with multielectrode recordings, and compared with network models. Health relatedness Persistent neural activity has consistently been observed in brain areas important in short-term memory, a central component of many cognitive abilities. Some mental disorders, such as schizophrenia, may involve deficits in short- term memory.