Date of Award

3-2026

Embargo Period

4-21-2026

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

College

College of Graduate Studies

First Advisor

Lori McMahon

Abstract

Cognitive deficits during abstinence are a hallmark of methamphetamine (meth) use and indicative of negative treatment outcomes. In rats, both long access meth self-administration and meth binge produce recognition memory deficits due to drug-induced plasticity within the perirhinal cortex (PRH). PRH projections are numerous and include the medial prefrontal cortex (mPFC) and the Nucleus Reuniens (NRe). In the first study, the role of the PRH-mPFC reciprocal circuit in novel object recognition memory was investigated by infusing an rgAAV encoding GFP-tagged Cre recombinase into the PRH or the mPFC. Following surgery, rats explored objects. During exploration, PRH neurons receiving input from the mPFC were activated by exploration of novel and familiar objects. In contrast, PRH neurons providing input to the mPFC were disproportionately activated by novel objects. The percentage of Fos + cells in the PRH positively correlated with recognition memory. Flow of communication appears to be from the PRH to the mPFC. In agreement with this proposed directionality, chemogenetic inhibition of the PRH-mPFC circuit impaired object recognition memory, whereas chemogenetic activation in animals with a history of long access meth self-administration reversed the meth-induced recognition memory deficit.

In our second study, the function of neurons in the NRe following a meth binge was investigated, as very little is known regarding the electrophysiological function of NRe neurons even under healthy conditions. This study serves to establish a baseline of neuronal excitability and synaptic activity within the NRe in control adult male Long-Evans rats and xv to determine the impact of meth on NRe neuronal function during abstinence from meth use, when cognitive deficits are known to occur. We found that during abstinence from meth use, sEPSC and sIPSC frequency is decreased, while amplitude for both is increased. Additionally, in current-clamp recordings of NRe neurons, we observed three distinct neuron firing patterns under control conditions and found no impact of meth on these patterns. Overall, the findings from these 2 studies inform future work aimed at understanding the role of the PRH, mPFC, NRe, and their connectivity in meth-associated memory deficits.

Rights

Copyright is held by the author. All rights reserved.

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