A circuit mechanism for differentiating positive and negative associations
The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Synaptic plasticity in the basolateral amygdala complex (BLA) mediates the acquisition of associative memories,...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2016
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| Online Access: | http://hdl.handle.net/1721.1/102520 https://orcid.org/0000-0003-2371-5706 https://orcid.org/0000-0002-1410-8675 https://orcid.org/0000-0003-0652-5652 https://orcid.org/0000-0002-4191-6926 https://orcid.org/0000-0002-4506-8813 |
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| author | Namburi, Praneeth Beyeler, Anna Yorozu, Suzuko Calhoon, Gwendolyn G. Wichmann, Romy Holden, Stephanie S. Mertens, Kim L. Wickersham, Ian R. Gray, Jesse M. Halbert, Sarah Anahtar, Melodi N. Felix-Ortiz, Ada Celis Tye, Kay |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Namburi, Praneeth Beyeler, Anna Yorozu, Suzuko Calhoon, Gwendolyn G. Wichmann, Romy Holden, Stephanie S. Mertens, Kim L. Wickersham, Ian R. Gray, Jesse M. Halbert, Sarah Anahtar, Melodi N. Felix-Ortiz, Ada Celis Tye, Kay |
| author_sort | Namburi, Praneeth |
| collection | MIT |
| description | The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Synaptic plasticity in the basolateral amygdala complex (BLA) mediates the acquisition of associative memories, both positive and negative. Different populations of BLA neurons may encode fearful or rewarding associations, but the identifying features of these populations and the synaptic mechanisms of differentiating positive and negative emotional valence have remained unknown. Here we show that BLA neurons projecting to the nucleus accumbens (NAc projectors) or the centromedial amygdala (CeM projectors) undergo opposing synaptic changes following fear or reward conditioning. We find that photostimulation of NAc projectors supports positive reinforcement while photostimulation of CeM projectors mediates negative reinforcement. Photoinhibition of CeM projectors impairs fear conditioning and enhances reward conditioning. We characterize these functionally distinct neuronal populations by comparing their electrophysiological, morphological and genetic features. Overall, we provide a mechanistic explanation for the representation of positive and negative associations within the amygdala. |
| first_indexed | 2024-09-23T16:56:42Z |
| format | Article |
| id | mit-1721.1/102520 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:56:42Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1025202022-10-03T09:18:41Z A circuit mechanism for differentiating positive and negative associations Namburi, Praneeth Beyeler, Anna Yorozu, Suzuko Calhoon, Gwendolyn G. Wichmann, Romy Holden, Stephanie S. Mertens, Kim L. Wickersham, Ian R. Gray, Jesse M. Halbert, Sarah Anahtar, Melodi N. Felix-Ortiz, Ada Celis Tye, Kay Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Picower Institute for Learning and Memory Namburi, Praneeth Beyeler, Anna Calhoon, Gwendolyn G. Halbert, Sarah Wichmann, Romy Holden, Stephanie S. Mertens, Kim L. Anahtar, Melodi N. Felix-Ortiz, Ada Celis Wickersham, Ian R. Tye, Kay The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Synaptic plasticity in the basolateral amygdala complex (BLA) mediates the acquisition of associative memories, both positive and negative. Different populations of BLA neurons may encode fearful or rewarding associations, but the identifying features of these populations and the synaptic mechanisms of differentiating positive and negative emotional valence have remained unknown. Here we show that BLA neurons projecting to the nucleus accumbens (NAc projectors) or the centromedial amygdala (CeM projectors) undergo opposing synaptic changes following fear or reward conditioning. We find that photostimulation of NAc projectors supports positive reinforcement while photostimulation of CeM projectors mediates negative reinforcement. Photoinhibition of CeM projectors impairs fear conditioning and enhances reward conditioning. We characterize these functionally distinct neuronal populations by comparing their electrophysiological, morphological and genetic features. Overall, we provide a mechanistic explanation for the representation of positive and negative associations within the amygdala. National Institute of Mental Health (U.S.) (R01-MH102441-01) National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (DP2-DK-102256-01) JPB Foundation Brain & Behavior Research Foundation Klingenstein Foundation Whitehall Foundation Alfred P. Sloan Foundation Singleton Fellowship MIT Presidential Marcus Fellowship to Honor Norman B. Leventhal Whitaker Foundation (Fellowship) Swiss National Science Foundation (Fellowship) Massachusetts Institute of Technology. Simons Center for the Social Brain (Postdoctoral Fellowship) NWO of the Netherlands (Rubicon Award) McGovern Institute for Brain Research at MIT (Seed Grant) Picower Institute for Learning and Memory (Seed Grant) Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences (Seed Grant) Massachusetts Institute of Technology. Simons Center for the Social Brain (Seed Grant) National Institute of Mental Health (U.S.) (BRAIN Initiative Award) National Eye Institute (BRAIN Initiative Award) National Institute of Neurological Disorders and Stroke (U.S.) (BRAIN Initiative Award U01-MH106018) National Institute of Neurological Disorders and Stroke (U.S.) (BRAIN Initiative Award U01-NS090473) National Science Foundation (U.S.) (IOS-1451202) 2016-05-18T13:58:05Z 2016-05-18T13:58:05Z 2015-04 2014-04 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/102520 Namburi, Praneeth, Anna Beyeler, Suzuko Yorozu, Gwendolyn G. Calhoon, Sarah A. Halbert, Romy Wichmann, Stephanie S. Holden, et al. “A Circuit Mechanism for Differentiating Positive and Negative Associations.” Nature 520, no. 7549 (April 30, 2015): 675–78. https://orcid.org/0000-0003-2371-5706 https://orcid.org/0000-0002-1410-8675 https://orcid.org/0000-0003-0652-5652 https://orcid.org/0000-0002-4191-6926 https://orcid.org/0000-0002-4506-8813 en_US http://dx.doi.org/10.1038/nature14366 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Namburi, Praneeth Beyeler, Anna Yorozu, Suzuko Calhoon, Gwendolyn G. Wichmann, Romy Holden, Stephanie S. Mertens, Kim L. Wickersham, Ian R. Gray, Jesse M. Halbert, Sarah Anahtar, Melodi N. Felix-Ortiz, Ada Celis Tye, Kay A circuit mechanism for differentiating positive and negative associations |
| title | A circuit mechanism for differentiating positive and negative associations |
| title_full | A circuit mechanism for differentiating positive and negative associations |
| title_fullStr | A circuit mechanism for differentiating positive and negative associations |
| title_full_unstemmed | A circuit mechanism for differentiating positive and negative associations |
| title_short | A circuit mechanism for differentiating positive and negative associations |
| title_sort | circuit mechanism for differentiating positive and negative associations |
| url | http://hdl.handle.net/1721.1/102520 https://orcid.org/0000-0003-2371-5706 https://orcid.org/0000-0002-1410-8675 https://orcid.org/0000-0003-0652-5652 https://orcid.org/0000-0002-4191-6926 https://orcid.org/0000-0002-4506-8813 |
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