By Mark Andermann and Arthur Sugden

Image courtesy of Arthur Sugden

Imagine you are a kid walking by a pair of golden arches and soon after, you start munching on a delicious burger. Later that night, as you’re lying awake in bed in the dark, you might vividly recall these golden arches, then the burger.. Wait! The arches mean I will get burgers!

What is happening in your brain during this process? We know that sensory experiences activate brain-wide patterns of neurons. During subsequent quiet periods, memories of salient and unexpected recent experiences may become consolidated via synchronous reactivation of these patterns throughout sensory cortex, amygdala, and hippocampus. Reactivation of recent experiences has been observed in prefrontal, motor, and primary sensory cortices, and is often synchronized with moments of increased sharp-wave ripple activity and associated replay of the experience in hippocampus. Such distributed reactivations of recent salient experiences have been hypothesized to promote memory consolidation, in part by selectively strengthening connections between neurons representing task-relevant information while globally weakening other connections.

A key hub that links the hippocampus, sensory cortex, and amygdala is the lateral visual association cortex, a region that integrates cue and outcome information and is necessary for offline memory consolidation and remote recall of salient cue-outcome associations. Recently, human neuroimaging studies reported preferential reactivation of salient experiences in lateral visual association cortex. Lateral visual association cortex becomes active during hippocampal ripple events, including during voluntary recall. However, the circuit-level effects of reactivation are not well understood, as previous studies of reactivation have not tracked large-scale activity patterns across days.

In recent work supported by the HBI Bipolar Disorder Seed Grant, supported by the Dauten Family Foundation, we used two-photon calcium imaging to track the same neurons in visual association cortex across days during learning of a visual discrimination task. In this way, we could characterize offline reactivations of sensory cues following each training session throughout learning, and the next-day changes in the response properties and functional connectivity of cells that participate in these reactivations. During quiet waking, we observed brief reactivations of patterns of cortical activity that matched those previously evoked by specific sensory cues. These cortical reactivation events were synchronized with hippocampal ripple activity. The rate of reactivations was higher for salient cues and following sessions with poor task performance early in learning, and predicted behavioral improvement in the following session. Critically, our long-term imaging approach revealed that cells that participated in cue reactivations following a day’s training session exhibited bidirectional changes in their next-day functional connectivity with the local network. Our findings suggest that different flavors of reactivation of previous cue presentations may selectively strengthen relevant ensembles of neurons encoding both the cue and the associated reward, while weakening intermingled ensembles of putatively task-irrelevant neurons. We hope this work inspires others to investigate the nature and consequences of normal and pathological recall of salient recent experiences at cellular and subcellular resolution.

Mark Andermann is and Associate Professor in Medicine at Harvard Medical School/Beth Israel Deaconess Medical Center.

Arthur Sugden is a postdoc in the lab of Mark Andermann at Harvard Medical School/Beth Israel Deaconess Medical Center.

Learn more in the original research article:

Cortical reactivations of recent sensory experiences predict bidirectional network changes during learning. Sugden AU, Zaremba JD, Sugden LA, McGuire KL, Lutas A, Ramesh RN, Alturkistani O, Lensjø KK, Burgess CR, Andermann ML. Nature Neuroscience, 2020.

This article will also appear in the HMS Neurobiology newsletter, The Action Potential.