Date of Award

2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

First Advisor

John T. Green

Abstract

Operant (instrumental) conditioning is a laboratory model of voluntary behavior. In its simplest form, performing a particular response, such as a lever press, leads to delivery of a reinforcing outcome (e.g., a sucrose pellet). Operant behaviors can be associated with preceding stimuli (“habits”) or outcomes (“goal-directed actions”). A factor that influences performance of operant behaviors is the context in which they are learned. Contexts can be defined as background stimuli that are present during behavior. For example, eating dessert may occur in the context of a restaurant and the sated feeling of a finished meal. The context for eating dessert, therefore, might include both the exteroceptive environment of restaurants as well as the interoceptive state of satiety. Previous work has shown that a region of the rodent medial prefrontal cortex, the prelimbic cortex (PL), is important for contextual modulation of operant behavior and for operant responding that is goal-directed. For example, pharmacological inactivation of the PL reduces operant responding only when the behavior is tested in its acquisition context. Previous work, however, has generally been limited to food and drug reinforcers and exteroceptive contexts (e.g., conditioning boxes with particular features). This dissertation investigates the involvement of the PL in non-consummatory reinforcers and interoceptive contexts as well as the cellular mechanisms and associated neural circuitry involved in contextually-mediated operant behavior more generally. First, we show using a pharmacological inactivation procedure, that the PL is necessary for context (the testing box) to promote the performance of an operant behavior whose reinforcer is the opportunity to perform a second behavior rather than receipt of a food pellet. Then, again using pharmacological inactivation, we show that the PL is necessary for interoceptive contexts (either hunger or stress state) to serve as acquisition contexts. Next, we show that dopamine receptor antagonism in the PL during acquisition prevents the expression of context-specific responding. Finally, we show that the ventral hippocampus, which has mono- and multisynaptic connections with the PL, is involved in contextual modulation of operant responding. Specifically, we show that chemogenetic inhibition of the ventral hippocampus, through activation of inhibitory receptors expressed in ventral hippocampal neurons, attenuates operant responding in its acquisition context. Collectively, the research presented in this dissertation supports the role of the PL in contextual modulation of operant behavior, where context includes both exteroceptive and interoceptive background stimuli. Additionally, we found support for the idea that dopaminergic innervation of the PL is necessary for the integration of contextual information with operant response learning. Finally, our results suggest that the ventral hippocampus likely contributes to contextual information processing by the PL.

Language

en

Number of Pages

233 p.

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