The Role of Glutamate in the Medial Prefrontal Cortex in the Acquistion and Expression of Conditioned Approach

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Psychology

Grantor

The Graduate School and University Center of The City University of New York

Year dc:date.available

2024

Author dc:creator

• Nisanov, Rudolf

Advisor dc:contributor.advisor

• Robert Ranaldi

Committee members dc:contributor.committeemember

• Emily Jones
• Bertram Ploog
• Richard Bodnar

• Applied Behavior Analysis
• Behavioral Neurobiology
• Molecular and Cellular Neuroscience
• Glutamate
• Prefrontal Cortex
• Conditioned Approach
• Learning
• DREADDs
• RNAscope

Repository record dc:identifier

https://academicworks.cuny.edu/gc_etds/5633

OAI identifier oai:identifier

oai:academicworks.cuny.edu:gc_etds-6744