The avalanche of memory: Recent feelings of familiarity, and their resultant DA nuclei activity, unlock the brain’s subsequent ability to reactivate memories

• Published in: bioRxiv
• Main Authors: Dougherty, Matthew R., Patil, Anuya, Duncan, Katherine D.
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Laboratory 02.06.2025
• Edition: 1.3
• Subjects: Neuroscience; episodic memory; fMRI; familiarity; novelty; reinstatement; retrieval; neuromodulators; acetylcholine; human; dopamine
• ISSN: 2692-8205
• DOI: 10.1101/2025.03.28.646007

Memory retrieval is notoriously variable. Various neurocognitive states have been theorized to affect retrieval success from moment to moment, but the presence and catalysts of these states in the human brain remain largely understudied. Building on previous work, we studied how recent memory experiences (i.e. novelty vs. familiarity) and their corresponding neural activity prepare the brain to reactivate memories. Our data uncover a pronounced neural bias, whereby regions representing episodic information fail to reactivate memories following recent experiences of novelty. Drawing on computational models, we hypothesized that novelty-evoked activity in cholinergic nuclei underlie this bias. The data revealed an unexpected alternative mediator of memory reactivation in response to recent novelty, namely recent dopaminergic nuclei activity. By identifying dopamine as a potential mediator of retrieval variability, our results challenge existing models and open new avenues for investigating how neuromodulatory states dynamically shape memory accessibility.