Adaptable behavior from anatomically fixed neural circuits : investigations into the synaptic bases of learning and ethanol pharmacology
Abstract/Contents
- Abstract
- The brain must strike a balance between reliable information processing and adaptation to an ever-changing environment. At a gross anatomical level, the brain's wiring diagram is believed to be relatively set after development. Therefore, a fundamental question arises: how does stereotyped wiring lead to flexible dynamics, computation, and behavior? This dissertation will explore this question through the lens of 2 phenomena -- the activity dependent strengthening of neural circuits and the pharmacology of ethyl alcohol. Chapter 1- Neurons are known to modify synaptic weights based on their history of coincident activity patterns, termed Hebbian plasticity. In the first study, I tested whether Hebbian potentiation of synapses in the hippocampus or striatum play a causal role in learning. Using the most specific manipulation of synaptic potentiation that we are aware of (Stx3 cKO), I tested a battery of behaviors that are known to require either the hippocampus or striatum. Much to our surprise, Stx3 cKO did not affect most behaviors we tested. However, hippocampal potentiation was critical for novelty-driven spatial learning. Further, we found that spatial/contextual coding was intact after Stx3 cKO, explaining our demonstration of normal spatial learning, and contextual novelty coding was greatly reduced after Stx3 cKO. Lastly, there were two other deficits related to reward and novelty coding that warrant further study. Over-all, our data refine the proposed role of synaptic potentiation -- from an all-encompassing learning signal to a synaptic mechanism for salience encoding. Chapter 2 -- A fixed neural circuit can update dynamics when a psychoactive sub-stance is applied. Indeed, the study of drugs of abuse has yielded insights into the basic biology of the brain. For example, the endogenous opioid and endocannabinoid systems were discovered through investigation of the pharmacological action of opioids and cannabinoids, respectively. In the second study, I continued this rich history by investigating the pharmacology of ethyl alcohol (EtOH). I found that EtOH reduces GABA co-release from dopamine neurons, a recently discovered property of dopamine neurons that has the potential to powerfully modulate brain-wide neural activity. Digging into the mechanism revealed that EtOH was not directly affecting GABA co-release, but rather EtOH's metabolite, acetaldehyde was out-competing GABA's precursor for access to the enzyme ALDH1a1.
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 | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Kaganovsky, Konstantin |
|---|---|
| Degree supervisor | Ding, Jun (Jun B.) |
| Degree supervisor | Südhof, Thomas C |
| Thesis advisor | Ding, Jun (Jun B.) |
| Thesis advisor | Südhof, Thomas C |
| Thesis advisor | Hestrin, Shaul |
| Thesis advisor | Luo, Liqun, 1966- |
| Thesis advisor | Shah, Nirao |
| Degree committee member | Hestrin, Shaul |
| Degree committee member | Luo, Liqun, 1966- |
| Degree committee member | Shah, Nirao |
| Associated with | Stanford University, Neurosciences Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Konstantin Kaganovsky. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/wq118ms5184 |
Access conditions
- Copyright
- © 2022 by Konstantin Kaganovsky
- License
- This work is licensed under a Creative Commons Attribution Non Commercial No Derivatives 3.0 Unported license (CC BY-NC-ND).
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