Convergent dopamine and serotonin reward signals govern associative learning
Abstract/Contents
- Abstract
- In mammals, midbrain dopamine (DA) neurons in the ventral tegmental area (VTA) have long been thought to play a critical role in pavlovian learning because they respond to rewards, acquire responses to reward predictive cues, and project to limbic structures important for motivated behaviors. Now, there is mounting evidence that serotonin (5-hydroxytryptamine; 5HT) neurons in the dorsal raphe (DR) share these properties. This suggests limbic circuits are under coordinated neuromodulatory control as animals form new associations, and begs the question: how are converging DA and 5HT signals integrated to drive learning? In Chapter 1, I review current hypotheses about the functions of the DA and 5HT systems in reward learning, both individually and together. In Chapter 2, I present original research beginning with the development of a double transgenic model enabling simultaneous genetic access to the brain's DA and 5HT systems in mice. Neural circuit tracing with these mice identified the nucleus accumbens posterior medial shell as the limbic area with the greatest density of converging VTA DA and DR 5HT inputs. VTA DA axons in this target region were excited by rewards while DR 5HT axons were inhibited. Loss-of-function manipulations blunting both of these reward responses together, but not either one alone, disrupted learning and reduced reward consumption without being inherently aversive. Gain-of-function manipulations reproducing both reward responses, but not either one alone, were sufficient to drive acquisition of new cue-reward associations. Taken together, these data show that striatal integration of convergent DA and 5HT reward signals governs learning by gating reinforcement. Finally, in Chapter 3 I provide a discussion of these findings, potential mechanisms, and future directions.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Cardozo Pinto, Daniel Felipe |
|---|---|
| Degree supervisor | Malenka, Robert C |
| Thesis advisor | Malenka, Robert C |
| Thesis advisor | Eshel, Neir |
| Thesis advisor | Lammel, Stephan |
| Thesis advisor | Luo, Liqun, 1966- |
| Degree committee member | Eshel, Neir |
| Degree committee member | Lammel, Stephan |
| Degree committee member | Luo, Liqun, 1966- |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Neurosciences Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Daniel Felipe Cardozo Pinto. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/mk467wd1160 |
Access conditions
- Copyright
- © 2023 by Daniel Felipe Cardozo Pinto
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