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Os textos são da exclusiva responsabilidade dos autores All texts are of the exclusive responsibility of the authors PREFRONTAL CONTROL OF IMPULSIVE ACTION Masayoshi Murakami and Zachary F. Mainen Systems Neuroscience Laboratory, Champalimaud Neuroscience Programme, Instituto Gulbenkian de Ciência Grant nº 127/08 Abstract: Impulse control - withholding short term actions to achieve longer term goals - is an important facet of goaldirected behavior. In pathological condition, such as drug addiction and attention deficit hyperactivity disorder, people tend to impulsively choose small reward available immediately, not considering long-term cost/benefit. Frontal cortex has been hypothesized to exert top-down inhibition of impulsive actions, but little is known about the nature of the neural signals responsible for such control. In this project, we aim to develop a novel impulse control task in rats, test the causal involvement of frontal cortical areas in impulse control and investigate neural correlates of impulse control in frontal cortical areas. In the impulse control task, subjects interact with a waiting port and a reward port. While waiting inside the waiting port, two tones are generated, the first at a fixed short delay (0.4 s) and the second at a longer random delay (exponentially-distributed, minimum. 0.7 s). Responses to the reward port after the first tone garner a reward, but the amount is 4 times larger after the second tone. The waiting time of subjects varied randomly across trials. Neuronal activity responsible for impulse control should be stronger in the long waiting trials than the short waiting trials. We made single-unit recordings from medial and dorsomedial frontal cortex neurons with movable tetrodes, testing for signals that correlated on a trial-by-trial basis with waiting time. Twelve percent (28/238) of neurons in dorsomedial and medial frontal cortex showed activity that was correlated with and predicted waiting time. We observed nearly equal proportions of positive and negative correlations. Waitingpredictive neurons showed a variety of time courses of activity. The most frequent one was a phasic signal locked to waiting-port entry. This result reveals properties of single neuronal activity which might be responsible for top-down impulse control. To test for areas that may be causally involved in impulse control, we infused muscimol locally to inactivate medial and dorsomedial frontal cortex. Preliminary results have shown that the inactivation of mPFC indeed led to a decrease in the waiting time and a decrease in the patient trials.