Dissertations, Theses, and Capstone Projects

Date of Degree

6-2025

Document Type

Master's Thesis

Degree Name

Master of Science

Program

Cognitive Neuroscience

Advisor

Susana Mingote

Committee Members

Nesha Burghardt

Subject Categories

Cognitive Neuroscience | Other Neuroscience and Neurobiology | Systems Neuroscience

Keywords

Entorhinal Cortex, Latent Inhibition, Memory Interference

Abstract

Memory interference occurs when previously formed memories disrupt the acquisition or retrieval of new information. A prominent example of proactive interference is latent inhibition (LI), defined as a reduced ability to form or express Pavlovian associations with a stimulus following non-reinforced exposure. The interference-based model suggests that LI arises because the memory that the pre-exposed stimulus is inconsequential interferes with the memory that it predicts a reinforcer.

Because interference increases with age, identifying its neural basis may help prevent or slow cognitive decline. Prior studies using the LI paradigm implicate the entorhinal cortex (EC) in retrieving the memory that a pre-exposed stimulus is inconsequential. The EC is functionally divided into the medial EC, involved in spatial processing, and the lateral EC (LEC), associated with item-related memory. Given this distinction, we hypothesized that the LEC may be particularly important for LI, especially for stimuli like tones presented in a context. However, this has not been directly tested.

We used a chemogenetic approach to transiently inhibit excitatory neurons in the LEC during memory retrieval in an LI paradigm. Mice were pre-exposed to a tone without consequence and later conditioned to associate the tone with a mild shock. On the final test day, the tone was presented alone, and freezing behavior was quantified as a measure of tone fear memory.

Experiments 1 and 2 established parameters for a robust LI effect. In Experiment 3, chemogenetic inhibition of the LEC during retrieval attenuated the LI effect—pre-exposed mice froze at levels similar to non-pre-exposed controls—supporting a critical role for the LEC in retrieval-based memory interference.

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