Functional Dissociation within the Entorhinal Cortex for Memory Retrieval of an Association between Temporally Discontiguous Stimuli

Memory retrieval is thought to depend on the reinstatement of cortical memory representations guided by pattern completion processes in the hippocampus. The lateral entorhinal cortex (LEC) is one of the intermediary regions supporting hippocampal-cortical interactions and houses neurons that prospectively signal past events in a familiar environment. To investigate the functional relevance of the LEC's activity for cortical reinstatement, we pharmacologically inhibited the LEC and examined its impact on the stability of ensemble firing patterns in one of the LEC's efferent targets, the medial prefrontal cortex (mPFC). When male rats underwent multiple epochs of identical stimulus sequences in the same environment, the mPFC maintained a stable ensemble firing pattern across repetitions, particularly when the sequence included pairings of neutral and aversive stimuli. With LEC inhibition, the mPFC still formed an ensemble pattern that accurately captured stimuli and their associations within each epoch. However, LEC inhibition markedly disrupted its consistency across the epochs by decreasing the proportion of mPFC neurons that stably maintained firing selectivity for stimulus associations. Thus, the LEC stabilizes cortical representations of learned stimulus associations, thereby facilitating the recovery of the original memory trace without generating a new, redundant trace for familiar experiences. Failure of this process might underlie retrieval deficits in conditions associated with degeneration of the LEC, such as normal aging and Alzheimer's disease.

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Memory retrieval modulates spatial tuning of single neurons in the human entorhinal cortex

Nature Neuroscience ◽

10.1038/s41593-019-0523-z ◽

2019 ◽

Vol 22 (12) ◽

pp. 2078-2086 ◽

Cited By ~ 6

Author(s):

Salman E. Qasim ◽

Jonathan Miller ◽

Cory S. Inman ◽

Robert E. Gross ◽

Jon T. Willie ◽

...

Keyword(s):

Entorhinal Cortex ◽

Memory Retrieval ◽

Single Neurons ◽

Spatial Tuning

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Muscarinic activity in hippocampus and entorhinal cortex is crucial for spatial and fear memory retrieval

Pharmacological Reports ◽

10.1016/j.pharep.2019.02.004 ◽

2019 ◽

Vol 71 (3) ◽

pp. 449-456 ◽

Cited By ~ 1

Author(s):

Habiba Rashid ◽

Touqeer Ahmed

Keyword(s):

Entorhinal Cortex ◽

Memory Retrieval ◽

Fear Memory

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The Potentiation of Associative Memory by Emotions: An Event-Related FMRI Study

Advances in Neuroscience ◽

10.1155/2014/964024 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

David Luck ◽

Marie-Eve Leclerc ◽

Martin Lepage

Keyword(s):

Performance Improvement ◽

Entorhinal Cortex ◽

Associative Memory ◽

Temporal Lobe ◽

Memory Retrieval ◽

Medial Temporal Lobe ◽

Emotional Valence ◽

Neural Correlates ◽

Fmri Study ◽

The Right

Establishing associations between pieces of information is related to the medial temporal lobe (MTL). However, it remains unclear how emotions affect memory for associations and, consequently, MTL activity. Thus, this event-related fMRI study attempted to identify neural correlates of the influence of positive and negative emotions on associative memory. Twenty-five participants were instructed to memorize 90 pairs of standardized pictures during a scanned encoding phase. Each pair was composed of a scene and an unrelated object. Trials were neutral, positive, or negative as a function of the emotional valence of the scene. At the behavioral level, participants exhibited better memory retrieval for both emotional conditions relative to neutral trials. Within the right MTL, a functional dissociation was observed, with entorhinal activation elicited by emotional associations, posterior parahippocampal activation elicited by neutral associations, and hippocampal activation elicited by both emotional and neutral associations. In addition, emotional associations induced greater activation than neutral trials in the right amygdala. This fMRI study shows that emotions are associated with the performance improvement of associative memory, by enhancing activity in the right amygdala and the right entorhinal cortex. It also provides evidence for a rostrocaudal specialization within the MTL regarding the emotional valence of associations.

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Neurons remap to represent memories in the human entorhinal cortex

10.1101/433862 ◽

2018 ◽

Cited By ~ 2

Author(s):

Salman Qasim ◽

Jonathan Miller ◽

Cory S. Inman ◽

Robert E. Gross ◽

Jon T. Willie ◽

...

Keyword(s):

Entorhinal Cortex ◽

Neuronal Activity ◽

Memory Retrieval ◽

Medial Temporal Lobe ◽

Cell Activity ◽

Cued Recall ◽

General Mechanism ◽

Virtual Reality Environment ◽

Memory Representations ◽

Past Experiences

AbstractThe entorhinal cortex (EC) is known to play a key role in both memory and spatial navigation. Despite this overlap in spatial and mnemonic circuits, it is unknown how spatially responsive neurons contribute to our ability to represent and distinguish past experiences. Recording from medial temporal lobe (MTL) neurons in subjects performing cued recall of object–location memories in a virtual-reality environment, we identified “trace cells” in the EC that remap their spatial fields to locations subjects were cued to recall on each trial. In addition to shifting its firing field according to the memory cue, this neuronal activity exhibited a firing rate predictive of the cued memory’s content. Critically, this memory-specific neuronal activity re-emerged when subjects were cued for recall without entering the environment, indicating that trace-cell memory representations generalized beyond navigation. These findings suggest a general mechanism for memory retrieval via trace-cell activity and remapping in the EC.

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Time course of the dependence of associative memory retrieval on the entorhinal cortex

Neurobiology of Learning and Memory ◽

10.1016/j.nlm.2014.10.003 ◽

2014 ◽

Vol 116 ◽

pp. 155-161 ◽

Cited By ~ 2

Author(s):

Xi Chen ◽

Zhengli Liao ◽

Yin Ting Wong ◽

Yiping Guo ◽

Jufang He

Keyword(s):

Entorhinal Cortex ◽

Associative Memory ◽

Memory Retrieval ◽

Time Course

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Mapping sequence structure in the human lateral entorhinal cortex

eLife ◽

10.7554/elife.45333 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 12

Author(s):

Jacob LS Bellmund ◽

Lorena Deuker ◽

Christian F Doeller

Keyword(s):

Episodic Memory ◽

Entorhinal Cortex ◽

Memory Retrieval ◽

Temporal Structure ◽

Sequence Structure ◽

Temporal Memory ◽

Event Sequences ◽

Mapping Sequence ◽

Virtual City

Remembering event sequences is central to episodic memory and presumably supported by the hippocampal-entorhinal region. We previously demonstrated that the hippocampus maps spatial and temporal distances between events encountered along a route through a virtual city (Deuker et al., 2016), but the content of entorhinal mnemonic representations remains unclear. Here, we demonstrate that multi-voxel representations in the anterior-lateral entorhinal cortex (alEC) — the human homologue of the rodent lateral entorhinal cortex — specifically reflect the temporal event structure after learning. Holistic representations of the sequence structure related to memory recall and the timeline of events could be reconstructed from entorhinal multi-voxel patterns. Our findings demonstrate representations of temporal structure in the alEC; dovetailing with temporal information carried by population signals in the lateral entorhinal cortex of navigating rodents and alEC activations during temporal memory retrieval. Our results provide novel evidence for the role of the alEC in representing time for episodic memory.

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Structuring Time in Human Lateral Entorhinal Cortex

10.1101/458133 ◽

2018 ◽

Cited By ~ 1

Author(s):

Jacob L.S. Bellmund ◽

Lorena Deuker ◽

Christian F. Doeller

Keyword(s):

Episodic Memory ◽

Entorhinal Cortex ◽

Memory Retrieval ◽

Temporal Structure ◽

Event Structure ◽

Temporal Memory ◽

Event Sequences ◽

Entorhinal Region ◽

Virtual City

AbstractRemembering event sequences is central to episodic memory and thought to be supported by the hippocampal-entorhinal region. We previously demonstrated that the hippocampus maps spatial and temporal distances between events encountered along a fixed route through a virtual city (Deuker et al., 2016), but the content of entorhinal mnemonic representations remains unclear. Here, we demonstrate that, after learning, multi-voxel representations in the anterior-lateral entorhinal cortex (alEC) specifically reflect the temporal event structure. Holistic representations of the temporal structure related to memory recall and the temporal event structure could be reconstructed from entorhinal multi-voxel patterns. Our findings demonstrate representations of temporal structure in the alEC in line with temporal information carried by population signals in the lateral entorhinal cortex of navigating rodents and activations of its human homologue during temporal memory retrieval. Our results provide novel evidence for the role of the human alEC in representing time for episodic memory.

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