Hippocampal and Prefrontal Dynamics During Structural Learning

Relational or structural learning, which involves discerning relationships between ambiguous cues, is crucial for identifying patterns in events and is fundamental to episodic memory. My proposed PhD project aims to elucidate the role of hippocampal and prefrontal cortical neural dynamics and their cholinergic neuromodulation in facilitating these learning processes.

Building on my rotation projects, I will:
1. Employ chronic Neuropixels (NPX) recordings simultaneously in the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) of mice. These mice will learn and perform an odor sequence and reward association task that relies on nonspatial relational learning. This task allows detailed behavioral analysis utilizing reinforcement learning models to estimate the internal variables mice are utilizing to solve the task. We will combine this behavioral analysis with our neural recordings to understand how vHPC and PFC activity relates to relational learning.

2. During my rotation project, I observed a significant surge in acetylcholine (ACh) signaling within the vHPC during the initial learning phase of the task. This aligns with the vHPC's role in contextual information encoding. As mice achieved proficiency, this elevated cholinergic activity decreased, suggesting a shift from active contextual encoding to reliance on an established internal model. Conversely, the mPFC exhibited stable but gradually decreasing ACh signaling levels as task mastery was attained. This highlights the mPFC's role in the continuous refinement of learned associations and decision-making. We will follow up on these findings and investigate the roleof cholinergic modulation in vHPC and PFC dynamics during learning and performance of the task.

Overall we hypothesize a synergistic learning model where the vHPC establishes a contextual groundwork that the mPFC refines into an action strategy informed by learned values. Furthermore we hypothesise that cholinergic modulation of both vPHC and PFC is crucial for structural learning, with distinct roles in acquisition, retention, and the application of intricate relational information.