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Early remodeling of the neocortex upon episodic memory encoding.

Adam W Bero1, Jia Meng2, Sukhee Cho1

  • 1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139;

Proceedings of the National Academy of Sciences of the United States of America
|July 30, 2014
PubMed
Summary

Long-term memory formation involves early changes in the neocortex, not just the hippocampus. The medial prefrontal cortex (mPFC) is crucial for this process, regulating memory encoding and hippocampal activity.

Keywords:
hippocampuslearningneuroplasticityoptogeneticstranscriptome

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Systems Neuroscience

Background:

  • Long-term memory storage is traditionally attributed to hippocampal circuits initially, with neocortical reorganization occurring much later.
  • The precise timing and mechanisms of neocortical involvement in early memory encoding remain incompletely understood.

Purpose of the Study:

  • To investigate the early molecular, structural, and functional changes in the neocortex during long-term memory encoding.
  • To determine the real-time role of the medial prefrontal cortex (mPFC) in long-term memory formation and its influence on hippocampal circuits.

Main Methods:

  • Genome-wide RNA sequencing to identify transcriptional changes in the neocortex.
  • Ultrastructural imaging to visualize synaptic plasticity.
  • Whole-cell recording to assess synaptic function.
  • Temporally precise optogenetic inhibition of mPFC neurons during fear conditioning in mice.

Main Results:

  • Contextual fear conditioning induced rapid transcriptional, structural (synaptic active zone and postsynaptic density expansion), and functional (enhanced synaptic plasticity and efficacy) remodeling in the medial prefrontal cortex (mPFC).
  • Real-time optogenetic inhibition of the mPFC during memory encoding disrupted entorhinal-hippocampal circuit activation.
  • Inhibition of mPFC activity impaired the formation of long-term associative memories.

Conclusions:

  • Long-term memory encoding involves early remodeling of neocortical circuits, particularly the mPFC.
  • The mPFC plays a critical role in regulating encoding-induced hippocampal activation and the subsequent formation of long-term memories.
  • These findings offer new insights into memory processing in both healthy and diseased brain states.