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Ex Vivo Optogenetic Dissection of Fear Circuits in Brain Slices
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An infralimbic cortex neuronal ensemble encoded during learning attenuates fear generalization expression.

Rajani Subramanian1, Avery Bauman1, Olivia Carpenter1

  • 1Department of Psychological Science, Program in Neuroscience and Behavior, Vassar College, Poughkeepsie NY 12603 USA.

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|September 4, 2024
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Summary
This summary is machine-generated.

The infralimbic cortex (IL) regulates defensive behaviors during generalization. Neuronal ensembles in the IL suppress generalized freezing responses to ambiguous stimuli, with their activity attenuating generalization.

Keywords:
Contextual fearEngramExtinctionIndividual differencesPredator imminence continuum theoryRisk assessment

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Area of Science:

  • Neuroscience
  • Behavioral Neuroscience
  • Cognitive Neuroscience

Background:

  • Generalization enables adaptive behavior in changing environments.
  • The infralimbic (IL) cortex is implicated in generalization, but its mechanisms are unclear.
  • Neuronal ensembles (engrams) are fundamental units of memory.

Purpose of the Study:

  • To investigate the role of IL neuronal ensembles in generalization.
  • To determine if IL engrams contribute to generalized defensive responses.
  • To elucidate the mechanisms by which the IL regulates generalization.

Main Methods:

  • Chemogenetic manipulation of IL activity in mice during fear conditioning and generalization testing.
  • Activity-dependent neuronal tagging (ArcCreERT2 × eYFP) to identify IL neuronal ensembles.
  • Behavioral analysis of defensive states (scanning vs. freezing) in response to ambiguous stimuli.

Main Results:

  • IL activity regulates defensive behavior towards ambiguous stimuli.
  • Silencing IL neurons induced generalized freezing; stimulating IL neurons promoted scanning.
  • A specific IL Layer 2/3 neuronal ensemble was associated with the generalization stimulus.
  • Silencing this IL ensemble increased generalization; stimulating it reduced generalization.

Conclusions:

  • The IL plays a critical role in suppressing generalized responses.
  • IL neuronal ensembles formed during learning attenuate the expression of generalization.
  • These findings reveal a novel mechanism for controlling generalized threat responses.