Dissertation
Opposing regulation of fear and other contextual responses by the dorsal versus ventral lateral septum
Doctor of Philosophy (Ph.D.), Drexel University
Nov 2023
DOI:
https://doi.org/10.17918/00001961
Abstract
Mental health disorders affect a significant portion of the population, especially those characterized by emotional dysregulation. One major challenge against these psychopathologies is ineffective treatment, in part due to the presence of comorbid disorders, which increases the hurdle of systematic treatment. Therapeutic focus on a central brain region involved in a range of pathologies would open a potential new, targeted area for the treatment of affective psychopathologies. The Lateral Septum (LS) stands out as a crucial subcortical region involved in a wide range of affective behaviors, most notably those associated with opposing regulations of fear. However, the underlying mechanism responsible for this intriguing up- and down-regulation of fear-related behaviors by the LS is unknown. Potential explanations for these contrasting functions lie in the intrinsic differences between the dorsal (d) versus ventral (v) subregions of the LS, and their inputs from different hippocampal subregions. Here we show that optogenetic activation of hippocampal dCA1-to-dLS and vCA1-to-vLS pathways elicit opposite modulations on fear, with the former promoting or maintaining fear responses and the latter suppressing them. In alignment with these findings, our in vivo electrophysiology recordings reveal contrasting firing characteristics between the dLS and vLS neurons, wherein they exhibit selective or nonselective responses to fear compared to other affective contexts. Additionally, dLS and vLS neurons display distinct co-activation patterns within each subregion, and interestingly a fear procedure induces emerging dLSvLS correlative firing during post-training sleep, suggesting a potential role in memory consolidation. Overall, our results shed light on the intricate nature of the LS in fear regulation, highlighting the significance of subregional differences within the LS and their interaction with different hippocampal inputs. This research contributes to a more comprehensive understanding of the neural circuitry involved in affective processes, offering new avenues for potential treatments in the field of mental health.
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Details
- Title
- Opposing regulation of fear and other contextual responses by the dorsal versus ventral lateral septum
- Creators
- Candace Alicia Rizzi-Wise
- Contributors
- Dong V. Wang (Advisor)Wen-Jun Gao (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xii, 148 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 991021819115404721