Sleep deprivation affects fear memory consolidation: bi-stable amygdala connectivity with insula and ventromedial prefrontal cortex

Following learning, increased coupling between spindle oscillations in the medial prefrontal cortex (mPFC) and ripple oscillations in the hippocampus is thought to underlie memory consolidation. However, whether learning-induced increases in ripple-spindle coupling are necessary for successful memory consolidation has not been tested directly. In order to decouple ripple-spindle oscillations, here we chemogenetically inhibited parvalbumin-positive (PV+) interneurons, since their activity is important for regulating the timing of spiking activity during oscillations. We found that contextual fear conditioning increased ripple-spindle coupling in mice. However, inhibition of PV+ cells in either CA1 or mPFC eliminated this learning-induced increase in ripple-spindle coupling without affecting ripple or spindle incidence. Consistent with the hypothesized importance of ripple-spindle coupling in memory consolidation, post-training inhibition of PV+ cells disrupted contextual fear memory consolidation. These results indicate that successful memory consolidation requires coherent hippocampal-neocortical communication mediated by PV+ cells.

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Odor-evoked category reactivation in human ventromedial prefrontal cortex during sleep promotes memory consolidation

eLife ◽

10.7554/elife.39681 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 10

Author(s):

Laura K Shanahan ◽

Eva Gjorgieva ◽

Ken A Paller ◽

Thorsten Kahnt ◽

Jay A Gottfried

Keyword(s):

Prefrontal Cortex ◽

Memory Consolidation ◽

Slow Wave Sleep ◽

Human Subjects ◽

Memory Performance ◽

Memory Task ◽

Ventromedial Prefrontal Cortex ◽

Odor Cues ◽

Object Location Memory ◽

Level Information

Slow-wave sleep is an optimal opportunity for memory consolidation: when encoding occurs in the presence of a sensory cue, delivery of that cue during sleep enhances retrieval of associated memories. Recent studies suggest that cues might promote consolidation by inducing neural reinstatement of cue-associated content during sleep, but direct evidence for such mechanisms is scant, and the relevant brain areas supporting these processes are poorly understood. Here, we address these gaps by combining a novel olfactory cueing paradigm with an object-location memory task and simultaneous EEG-fMRI recording in human subjects. Using pattern analysis of fMRI ensemble activity, we find that presentation of odor cues during sleep promotes reactivation of category-level information in ventromedial prefrontal cortex that significantly correlates with post-sleep memory performance. In identifying the potential mechanisms by which odor cues selectively modulate memory in the sleeping brain, these findings bring unique insights into elucidating how and what we remember.

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Hippocampal CCR5/RANTES Elevations in a Rodent Model of Post-Traumatic Stress Disorder: Maraviroc (a CCR5 Antagonist) Increases Corticosterone Levels and Enhances Fear Memory Consolidation

Biomolecules ◽

10.3390/biom10020212 ◽

2020 ◽

Vol 10 (2) ◽

pp. 212 ◽

Cited By ~ 1

Author(s):

José Joaquín Merino ◽

Vilma Muñetón-Gomez ◽

César Muñetón-Gómez ◽

María Ángeles Pérez-Izquierdo ◽

María Loscertales ◽

...

Keyword(s):

Prefrontal Cortex ◽

Chronic Stress ◽

Memory Consolidation ◽

Stress Disorder ◽

Training Session ◽

Fear Memory ◽

Rodent Model ◽

Contextual Fear Conditioning ◽

Ccr5 Antagonist ◽

Contextual Fear

Background: Contextual fear conditioning (CFC) is a rodent model that induces a high and long-lasting level of conditioning associated with traumatic memory formation; this behavioral paradigm resembles many characteristics of posttraumatic stress disorder (PSTD). Chemokines (chemotactic cytokines) play a known role in neuronal migration and neurodegeneration but their role in cognition is not totally elucidated. Aim: We ascertain whether CCR5/RANTES beta chemokines (hippocampus/prefrontal cortex) could play a role in fear memory consolidation (CFC paradigm). We also evaluated whether chronic stress restraint (21 days of restraint, 6-h/day) could regulate levels of these beta chemokines in CFC-trained rats; fear memory retention was determined taking the level of freezing (context and tone) by the animals as an index of fear memory consolidation 24 h after CFC training session; these chemokines (CCR5/RANTES) and IL-6 levels were measured in the hippocampus and prefrontal cortex of chronically stressed rats, 24 h after CFC post-training, and compared with undisturbed CFC-trained rats (Experiment 1). In Experiment 2, rats received 1 mA of footshock during the CFC training session and fear memory consolidation was evaluated at 12 and 24 h after CFC training sessions. We evaluated whether RANTES levels could be differentially regulated at 12 and 24 h after CFC training; in Experiment 3, maraviroc was administered to rats (i.m: 100 mg/Kg, a CCR5 antagonist) before CFC training. These rats were not subjected to chronic stress restraint. We evaluated whether CCR5 blockade before CFC training could increase corticosterone, RANTES, or IL-6 levels and affects fear memory consolidation in the rats 24-h post-testing compared with vehicle CFC-trained rats. Results: Elevations of CCR5/RANTES chemokine levels in the hippocampus could have contributed to fear memory consolidation (24 h post-training) and chronic stress restraint did not affect these chemokines in the hippocampus; there were no significant differences in CCR5/RANTES levels between stressed and control rats in the prefrontal cortex (Experiment 1). In Experiment 2, hippocampal CCR5/RANTES levels increased and enhanced fear memory consolidation was observed 12 and 24 h after CFC training sessions with 1 mA of footshock. Increased corticosterone and CCR5/RANTES levels, as well as a higher freezing percentage to the context, were found at 24 h CFC post-testing in maraviroc-treated rats as compared to vehicle-treated animals (experiment-3). Conversely, IL-6 is not affected by maraviroc treatment in CFC training. Conclusion. Our findings suggest a role for a hippocampal CCR5/RANTES axis in contextual fear memory consolidation; in fact, RANTES levels increased at 12 and 24 h after CFC training. When CCR5 was blocked by maraviroc before CFC training, RANTES (hippocampus), corticosterone levels, and fear memory consolidation were greater than in vehicle CFC-trained rats 24 h after the CFC session.

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0314 Resilience to Inhibitory Deficits During Sleep Deprivation is Predicted by Gray Matter Volume in the Ventrolateral and Ventromedial Prefrontal Cortex

SLEEP ◽

10.1093/sleep/zsaa056.311 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A118-A119

Author(s):

W D Killgore ◽

N S Dailey ◽

A C Raikes ◽

J R Vanuk ◽

E Taylor ◽

...

Keyword(s):

Prefrontal Cortex ◽

Sleep Deprivation ◽

Gray Matter ◽

Gray Matter Volume ◽

Ventromedial Prefrontal Cortex ◽

Healthy Individuals ◽

Ventrolateral Prefrontal Cortex ◽

Matter Volume ◽

Inhibitory Capacity ◽

Reduced Volume

Abstract Introduction Stable, trait-like inter-individual resilience to sleep loss has been demonstrated for psychomotor vigilance, mood, subjective sleepiness, and some reasoning tasks, some of which have been associated with specific genetic or neurobiological markers. Resilience to executive control deficits induced by sleep deprivation (SD) has not been explored in terms of neurobiological markers. We, therefore, collected magnetic resonance imaging (MRI) scans of healthy individuals when well rested and correlated gray matter volume with resistance to inhibitory declines during 29 hours of SD. Methods Forty-five healthy individuals (22 female) ranging in age from 20 to 43 underwent structural MRI. Within 2-4 days after scanning, participants returned to the lab to undergo one night of SD, during which they completed a standard go/no-go task involving inhibitory processing every 4 hours. Scores were calculated as throughput (correct responses per working minute). The difference between performance in the evening (22:45) versus the performance the next morning (06:45) was calculated as an index of “inhibitory resilience.” Gray matter volume was regressed against the inhibitory resilience measure. Based on prior research, regions were constrained to the ventrolateral prefrontal cortex and ventromedial prefrontal cortex. Results Greater resilience against declines in inhibitory capacity during SD was predicted by 1) larger gray matter volume within the ventrolateral prefrontal cortex and 2) reduced volume within the ventromedial prefrontal cortex (p<.05, FWE cluster corrected). These two clusters contributed significant unique explanatory variance to the model (R2=.45, p<.0001). Conclusion The ability to sustain performance during an inhibitory go/no-go task during SD was predicted by greater gray matter volume within the ventrolateral prefrontal cortex, a region that has been previously associated with inhibitory capacity, and reduced volume within an area of the ventromedial prefrontal cortex, which is often related to the default mode network. Findings suggest that specific brain networks may confer task-specific resistance to SD. Support Defense Advanced Research Projects Agency, DARPA Young Faculty Award: DARPA-12-12-11-YFA-FP-029

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