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Related Experiment Video

Updated: Jul 5, 2025

Extinction Training During the Reconsolidation Window Prevents Recovery of Fear
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Coordinating brain-distributed network activities in memory resistant to extinction.

Charlie J Clarke-Williams1, Vítor Lopes-Dos-Santos1, Laura Lefèvre1

  • 1Medical Research Council Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX1 3TH, UK.

Cell
|January 19, 2024
PubMed
Summary
This summary is machine-generated.

Robust memories, like those driving cocaine-seeking behavior, are organized by coordinated brain activity. Specifically, a higher-order pattern of beta-frequency oscillations across multiple brain regions underlies memory retrieval and renewal.

Keywords:
amygdalaextinctionhippocampusmemorynucleus accumbensoscillationsprefrontal cortexrecallrenewalventral tegmental area

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Area of Science:

  • Neuroscience
  • Behavioral Neuroscience
  • Systems Neuroscience

Background:

  • Persistent memories, particularly those linked to maladaptive behaviors like addiction, are often resistant to extinction.
  • The neural basis for how widely distributed neuronal activity across multiple brain regions organizes these robust memory-guided behaviors remains unclear.

Purpose of the Study:

  • To investigate the collective organization of dispersed neuronal activities underlying persistent memory-guided behavior.
  • To explore the neural mechanisms behind the renewal of cocaine-associated memories after extinction.

Main Methods:

  • Simultaneous monitoring of neural activity in the prefrontal cortex, nucleus accumbens, amygdala, hippocampus, and ventral tegmental area (VTA) in mice.
  • Analysis of neural oscillations during memory recall, extinction, and renewal phases of a cocaine-associated memory.
  • Investigating the role of VTA output pathways and specific frequency bands (beta and theta) in memory expression.

Main Results:

  • A higher-order pattern of transiently coordinated, short-lived beta-frequency (15-25 Hz) activities was identified across multiple brain networks during memory retrieval.
  • A divergent pathway from VTA glutamatergic neurons, paced by a 4-Hz oscillation, was found to drive this multi-network beta-band coactivation.
  • Closed-loop, phase-informed suppression of this neural activity prevented the renewal of cocaine-biased behavior.

Conclusions:

  • Temporally structured coordination of brain-distributed neural activities, specifically through multi-network beta-band oscillations, may be a key organizational principle for robust memory expression.
  • This coordinated activity, driven by VTA pathways, is crucial for the retrieval and renewal of drug-associated memories.
  • Targeting these specific neural dynamics offers a potential strategy for preventing the relapse of maladaptive behaviors.