Dissertations, Theses, and Capstone Projects

Date of Degree

2-2024

Document Type

Dissertation

Degree Name

Ph.D.

Program

Psychology

Advisor

Robert Ranaldi

Committee Members

Emily Jones

Bertram Ploog

Richard Bodnar

Subject Categories

Applied Behavior Analysis | Behavioral Neurobiology | Molecular and Cellular Neuroscience

Keywords

Glutamate, Prefrontal Cortex, Conditioned Approach, Learning, DREADDs, RNAscope

Abstract

A series of experiments were conducted to assess the role of glutamatergic stimulation in the dorsal and ventral regions of the medial prefrontal cortex (mPFC) in both the acquisition and expression of reward-related learning using a Pavlovian conditioning paradigm, the conditioned-approach paradigm. Rats with surgically implanted cannulas were exposed to Pavlovian conditioning sessions that occurred on three alternative days (acquisition) or seven consecutive days (expression). These 60-min conditioning sessions consisted of 30 pairings of light (CS) and food pellets (US) presented under a random time schedule. After a two-day break, rats underwent a session with no CS or US and a CS-only (extinction) test session on the following day. For the acquisition of conditioned approach, NMDA receptors were blocked with AP5 prior to each of the three conditioning sessions. For expression, AMPA receptors were blocked with CNQX prior to the CS-only test session. The results from the acquisition experiments show substantially greater responding for the CS (conditioned approach) in rats with inhibited NMDA receptors in both regions of mPFC in comparison to control groups. In the expression experiments, however, inhibition of AMPA receptors in the dorsal region resulted in significant dose-dependent impairment of conditioned approach but in the ventral region it resulted in dose-dependent facilitation of conditioned approach in comparison to the respective control groups. An RNAscope was employed to assess whether the CS – a food-paired light stimulus –activated more neurons than the light stimulus not explicitly paired with food (neutral stimulus). The results revealed that the CS resulted in significantly higher neuronal activation than the non-CS and that the neuronal population that was affected were glutamatergic neurons. The final experiment used chemogenetics to inhibit glutamatergic projections from dmPFC to NAc, finding a significant impairment in conditioned approach expression. Confocal microscopy revealed the pathway originating from dmPFC glutamatergic cells to NAc, supporting the role of top-down executive control in learned behavior expression.

Download

Share

COinS