On a roll: Successful retrieval primes the brain to retrieve other memories via dopaminergic responses

Poster Session E - Monday, April 15, 2024, 2:30 – 4:30 pm EDT, Sheraton Hall ABC

Matthew Dougherty¹, Anuya Patil¹, Katherine Duncan¹; ¹University of Toronto

Which brain states prepare us to successfully retrieve memories? Animal models suggest that slowly changing concentrations of modulatory neurotransmitters, including acetylcholine, dopamine, and norepinephrine, may shape retrieval. In line with this possibility, our group previously found that novelty–a form of stimulus salience associated with neuromodulator release–decreased associative retrieval ability for multiple seconds (Patil & Duncan, 2018). Acetylcholine is the only novelty-evoked neuromodulator theorized to suppress retrieval by inhibiting pattern completion; therefore, we hypothesized that acetylcholine drove this finding. Here, we test this mechanism. Specifically, we used functional magnetic resonance imaging (fMRI, n=29) to test whether activation of cholinergic nuclei mediates novelty’s suppression of pattern completion, indexed with encoding-retrieval similarity (ERS). Inline with previous research, participants recalled fewer places and faces associated with words when novel objects preceded these words (t=-2.31, p<0.05). Preceding novel objects also reduced ERS across the ventral stream, consistent with suppressed pattern completion (all t>2.16, p<0.05). However, contrary to our hypothesis, neuromodulatory centers did not signal novelty in this task. Surprisingly, we found that both dopaminergic and cholinergic nuclei responded more to familiar objects, and the response in dopaminergic regions uniquely mediated subsequent ERS in the medial temporal lobe (MTL) cortex (indirect effect (ab)=0.0004, p<0.05). Our findings point to dopamine’s lingering influence over memory retrieval, expanding the landscape of mechanisms that prepare us to remember.

Topic Area: LONG-TERM MEMORY: Episodic