Optogenetic Manipulation of the Lateral Septum during Reward-Related Behaviors Restricted; Files Only
Kangovi, Anagha (Spring 2024)
Abstract
Reward-related behaviors are fundamental to survival and well-being, yet the underlying neural mechanisms are not completely understood. The lateral septum (LS) is a brain region intricately involved in mediating various behaviors, including fear conditioning, social interactions, memory acquisition, anxiety regulation, and aggressive behaviors. While there has been less focus on its involvement in reward, connections to reward centers such as the ventral tegmental area and nucleus accumbens suggest its potential role in influencing reward-related behaviors. This study aimed to investigate the role of LS neuronal activity in reward-related behaviors using optogenetic techniques in mice. Viral vectors expressing channelrhodopsin-2 (ChR2) were injected into the LS of experimental mice, while control mice received green fluorescent protein (GFP). Optical fibers were implanted for light delivery. Sucrose reward operant assays were conducted under both water-deprived and full-water access conditions. Additionally, an intracranial self-stimulation assay was performed. Optogenetic stimulation of LS neurons during the sucrose reward operant assay under water-deprived conditions did not significantly increase motivation to seek the sucrose reward, though it did increase the time taken to collect the sucrose reward. However, in full-water access conditions, stimulated mice exhibited a behavior wherein they sought LS stimulation but failed to receive the sucrose reward on many occasions. This suggests that LS stimulation can act as a reward itself, influencing behavior when there is less motivation to seek a sucrose reward. Furthermore, in the intracranial self-stimulation assay, experimental mice showed a significant preference for optogenetic stimulation as opposed to a lack of stimulation, indicating that LS stimulation served as a rewarding stimulus. These findings demonstrate that optogenetic manipulation of LS neuronal activity can modulate reward-related behaviors. Future studies could explore the role of specific LS projection populations and neuronal subtypes in mediating reward processing. Understanding the intricate circuitry and mechanisms underlying reward modulation by the LS could offer insights into various psychiatric disorders and potential therapeutic interventions.
Table of Contents
Introduction................................................................................................................................... 1
Lateral Septum Anatomy................................................................................................................. 1
Lateral Septum Function ................................................................................................................ 3
Lateral Septum and Reward ........................................................................................................... 4
Materials and Methods................................................................................................................. 5
Subjects ........................................................................................................................................... 5
Viruses ............................................................................................................................................ 6
Stereotaxic Surgery......................................................................................................................... 6
Optogenetics ................................................................................................................................... 6
Sucrose Reward Operant Assay...................................................................................................... 7
Intracranial Self-Stimulation Assay................................................................................................ 7
Histology and Imaging.................................................................................................................... 8
Data Analysis .................................................................................................................................. 8
Results ............................................................................................................................................ 8
Ferrule implants and viral expression in the lateral septum.......................................................... 8
Sucrose reward operant assay training during water deprivation................................................. 9
Effect of optogenetic excitation on sucrose reward operant assay behavior during water deprivation .................................................................................................................................... 11
Effect of optogenetic excitation on sucrose reward operant assay behavior during full water access ............................................................................................................................................ 13
Intracranial self-stimulation of the lateral septum ....................................................................... 15
Discussion .................................................................................................................................... 18 References.................................................................................................................................... 21
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File download under embargo until 24 May 2026 | 2024-04-10 00:16:40 -0400 | File download under embargo until 24 May 2026 |
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