The neural circuits underlying valence-guided decision making
Abstract/Contents
- Abstract
- This thesis presents two separate but related bodies of work. In the first half, I discuss the development of a new technology, frame-projected independent-fiber photometry (FIP), that allows simultaneous Ca2+ imaging of up to 7 different brain regions or axonal projections in awake behaving mice. I used this technique to reveal the different activation patterns of ventral tegmental area dopamine (VTA-DA) neurons during reward and punishment. One of my key findings was that the VTA-DA projection to the mPFC responds preferentially to shock rather than reward, suggesting that this region may be especially important in processing punishment in addition to its known role in decision making. This work led to the second half of my thesis where I used FIP along with two-photon Ca2+ imaging, optogenetics, and activity-dependent labeling to study projection-specific subpopulations of the mPFC during aversive experiences. I address how the mPFC projection to NAc (mPFC→NAc) encodes aversive outcomes to suppress reward-seeking in the face of a foot shock. By contrast, I found that the mPFC projection to VTA -- the brain's primary reward center -- does not play a role in the suppression of reward-seeking. First I used cellular resolution two-photon Ca2+ imaging to identify the specific subpopulation of mPFC projection neurons that encode the suppression of reward-seeking. I found that ensembles of mPFC→NAc neurons could robustly predict trial-by-trial suppression of reward-seeking, and that neurons predicting suppression also responded to foot shock. When looking at the activity of all shock-encoding mPFC→NAc neurons, these neurons were more active immediately prior to the suppression of reward-seeking. I then used an activity-dependent labeling strategy to specifically target mPFC→NAc neurons that respond to foot shock, and found that stimulation of this sparse projection could suppress reward-seeking. The work in this thesis suggests a highly specific designation for the mPFC neurons engaged in valence-guided decision making, depending both on projection targeting and functional activity during behavior.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Kim, Christina Kay |
|---|---|
| Associated with | Stanford University, Department of Neurosciences. |
| Primary advisor | Deisseroth, Karl |
| Thesis advisor | Deisseroth, Karl |
| Thesis advisor | Giocomo, Lisa |
| Thesis advisor | Hestrin, Shaul |
| Thesis advisor | Huguenard, John |
| Advisor | Giocomo, Lisa |
| Advisor | Hestrin, Shaul |
| Advisor | Huguenard, John |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Christina Kay Kim. |
|---|---|
| Note | Submitted to the Department of Neurosciences. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Christina Kim
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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