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The Journal of Neuroscience, November 19, 2003, 23(33):10577-10584

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Behavioral/Systems/Cognitive
Inhibiting the Expression of a Classically Conditioned Behavior Prevents Its Extinction

David J. Krupa and Richard F. Thompson

Neuroscience Program, University of Southern California, Los Angeles, California 90089-2520

The underlying neuronal substrates and behavioral properties that might mediate extinction of the classically conditioned eye-blink response (CR) were examined. Four groups of rabbits were trained to perform the CR. Two of the groups then received either three or six sessions of tone-alone extinction training while the motor nuclei that mediate expression of the CR (facial nucleus and accessory abducens) were reversibly inactivated with microinjections of the GABA agonist muscimol. After these inactivation extinction sessions, rabbits received four more extinction sessions without inactivation. Two groups of controls received either three or six extinction sessions while saline vehicle was infused into the motor nuclei, followed by four sessions with no infusions. Saline infusions had no effect on extinction, and controls extinguished the CR normally over the first three to four sessions. In contrast, muscimol inactivation of the motor nuclei completely prevented any performance of CRs during the three or six inactivation extinction sessions. At the start of the four extinction sessions without inactivation, rabbits performed CRs at the same rate and amplitude as controls on their first extinction sessions. The muscimol rabbits then extinguished the CR normally over the four sessions without inactivation. In short, inactivation of the motor nuclei completely prevented any extinction of the eye-blink CR with no effect on subsequent extinction without inactivation. These results are discussed in terms of possible neuroanatomical loci that might mediate the extinction process as well as how effects of manipulating CR performance during extinction may affect the extinction process.

Key words: learning; memory; eye-blink; extinction; motor nuclei; classical conditioning

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Received June 13, 2003; revised September 26, 2003; accepted September 29, 2003.

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