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Susumu Tonegawa. Hueske, Emily (Emily Anna-Virginia) Massachusetts Institute of Technology. Dept. of Brain and Cognitive Sciences. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences 2011-08-18T19:13:35Z 2011-08-18T19:13:35Z 2011 2011 http://hdl.handle.net/1721.1/65286 744953465 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011. Cataloged from PDF version of thesis. Vita. Includes bibliographical references. Midbrain dopamine has demonstrated roles in locomotion, motivation, associative learning, habit formation, action selection and cognition. The many functions of dopamine can be attributed to the multiple projection targets of midbrain dopaminergic nuclei and to the multiple characteristic modes of dopamine neuron firing, tonic and phasic. Phasic transients of midbrain dopamine neurons are widely reported to signal errors conveying discrepancies between predicted and actual reward. Knocking out NMDARs in dopamine neurons has been shown to attenuate dopaminergic phasic firing providing a potential model for delineating the functions of tonic and phasic dopamine. In order to study the role of dopamine neuron NMDARs in rewardcontingent learning, we developed an auditory-cued binary choice task using complex auditory stimuli that lend themselves to efficient learning as well as morphing. We report that mice lacking NMDARs in dopamine neurons have a deficit in learning an auditory two-alternative choice task, in the absence of changes in response vigor. Dopamine neurons respond phasically to rewards as well as reward predictive cues. Updating the reward predictive value of cues is fundamental to shaping adaptive patterns of behavior and decision-making. Given the hypothesized role of dopamine in the updating of reward predictive cues, we were interested to see if an influence of reward history would be evident in the choices made by mice lacking dopamine neuron NMDARs. In an auditory-cued binary choice task, we find an influence of the difficulty of prior successes on subsequent decisions when mice are challenged with varying degrees of discrimination difficulty. In mice lacking dopamine neuron NMDARs, we find a lack of influence of prior decision difficulty. Our results identify a modulation of choices by prior decision difficulty in mice, and demonstrate the dopamine-dependent nature of this modulation. These findings are consistent with a role for dopamine neuron phasic firing in the trial-by-trial shaping of reward contingent learning. by Emily Hueske. Ph.D. 158 p. eng Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Brain and Cognitive Sciences. A role for Dopamine neuron NMDA receptors in learning and decision-making The role of Dopamine neuron NMDAs in learning and decision-making Thesis application/pdf Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="28b26fe3-6952-41b3-bfc1-706c0c76d2b3"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>A role for Dopamine neuron NMDA receptors in learning and decision-making</Title> <Subtitle>The role of Dopamine neuron NMDAs in learning and decision-making</Subtitle> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2011</PublicationDate> <Authors> <Author> <DisplayName>Hueske, Emily (Emily Anna-Virginia)</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Brain and Cognitive Sciences.</Keyword> <Abstract>Midbrain dopamine has demonstrated roles in locomotion, motivation, associative learning, habit formation, action selection and cognition. The many functions of dopamine can be attributed to the multiple projection targets of midbrain dopaminergic nuclei and to the multiple characteristic modes of dopamine neuron firing, tonic and phasic. Phasic transients of midbrain dopamine neurons are widely reported to signal errors conveying discrepancies between predicted and actual reward. Knocking out NMDARs in dopamine neurons has been shown to attenuate dopaminergic phasic firing providing a potential model for delineating the functions of tonic and phasic dopamine. In order to study the role of dopamine neuron NMDARs in rewardcontingent learning, we developed an auditory-cued binary choice task using complex auditory stimuli that lend themselves to efficient learning as well as morphing. We report that mice lacking NMDARs in dopamine neurons have a deficit in learning an auditory two-alternative choice task, in the absence of changes in response vigor. Dopamine neurons respond phasically to rewards as well as reward predictive cues. Updating the reward predictive value of cues is fundamental to shaping adaptive patterns of behavior and decision-making. Given the hypothesized role of dopamine in the updating of reward predictive cues, we were interested to see if an influence of reward history would be evident in the choices made by mice lacking dopamine neuron NMDARs. In an auditory-cued binary choice task, we find an influence of the difficulty of prior successes on subsequent decisions when mice are challenged with varying degrees of discrimination difficulty. In mice lacking dopamine neuron NMDARs, we find a lack of influence of prior decision difficulty. Our results identify a modulation of choices by prior decision difficulty in mice, and demonstrate the dopamine-dependent nature of this modulation. These findings are consistent with a role for dopamine neuron phasic firing in the trial-by-trial shaping of reward contingent learning.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>