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Investigating the Role of Nucleus Accumbens Neurons in Reward Seeking

Schall, Terra (2024) Investigating the Role of Nucleus Accumbens Neurons in Reward Seeking. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Reward seeking is an innate behavior that unfolds through a series of preceding mental and behavioral processes. Maladaptive reward seeking is characteristic of a variety of mental disorders, making it a paramount behavior to begin to understand health and disease. The nucleus accumbens (NAc) regulates reward-motivated behavior for a variety of different rewards. Following cocaine exposure, the NAc undergoes synaptic adaptations of which their functional states of one substrate, silent synapses, underlie the state of the cocaine seeking behavior. Less is clear about silent synapses in response to nondrug rewards. Here, I began to characterize the synaptic adaptations within the NAc that occur with exposure to sucrose and found that sucrose experience leads to a higher percentage of silent synapses within the NAc than without sucrose experience. This finding suggests that the NAc undergoes synaptic changes in response to nondrug rewards and prompts the investigation into the population level changes that may underlie reward seeking. The temporal dynamics of NAc neurons that enable freely behaving animals to seek a reward remain elusive. We recorded GCaMP-based Ca2+ activity from individual NAc medium spiny neurons (MSNs) when mice performed lever-presses for sucrose. MSNs exhibited three temporally sequenced clusters, defined by times at which they exhibited increased Ca2+ activity: 0, -2.5 or -5 sec relative to the lever pressing for sucrose. Dopamine D1 receptor (D1)-expressing MSNs and D2-MSNs formed most of the -5-sec versus -2.5-sec clusters, respectively, while both neuronal subtypes were represented in the 0-sec cluster. We found that pre-press activity patterns of D1- or D2-MSNs predict subsequent lever-presses. Inhibiting D1-MSNs at -5 sec or D2-MSNs at -2.5 sec, but not at other timepoints, reduced lever pressing for sucrose. We propose that these time-specific activities of D1- and D2-MSNs mediate key temporal features of the NAc through which reward motivation initiates reward seeking behavior.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Schall, Terratas240@pitt.edutas240
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee CoChairDong, Yanyandong@pitt.edu
Committee CoChairRunyan, Carolinerunyan@pitt.edu
Committee MemberVazquez, Albertoalv15@pitt.edu
Committee MemberSchluter, Oliverschluter@pitt.edu
Committee MemberHuang, Yanhuayhhuang@pitt.edu
Committee MemberLin, Da-Tingda-ting.lin@nih.gov
Date: 27 August 2024
Date Type: Publication
Defense Date: 18 April 2024
Approval Date: 27 August 2024
Submission Date: 31 May 2024
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 142
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: reward seeking, nucleus accumbens, sucrose
Date Deposited: 27 Aug 2024 14:23
Last Modified: 27 Aug 2024 14:23
URI: http://d-scholarship.pitt.edu/id/eprint/46451

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