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Updated: May 10, 2025

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning
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Infralimbic Projections to the Substantia Innominata-Ventral Pallidum Constrain Defensive Behavior during Extinction

Carolina Fernandes-Henriques1,2, Yuval Guetta3, Mia Sclar2

  • 1Biology Program, The Graduate Center, CUNY, New York 10016.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|April 22, 2025
PubMed
Summary
This summary is machine-generated.

The infralimbic (IL) cortex pathway to the substantia innominata-ventral pallidum (SI/VP) constrains fear responses during extinction learning. This pathway, distinct from the IL→basolateral amygdala (BLA) pathway, is crucial for regulating defensive behaviors.

Keywords:
amygdalafear extinctioninfralimbiclearningsubstantia innominataventral pallidum

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Area of Science:

  • Neuroscience
  • Behavioral Neuroscience
  • Learning and Memory

Background:

  • Fear extinction is vital for adapting to non-threatening stimuli.
  • The infralimbic (IL) cortex and basolateral amygdala (BLA) are known to mediate extinction memory retrieval.
  • IL pathways involved in extinction learning remain less understood.

Purpose of the Study:

  • To investigate the role of the IL→substantia innominata-ventral pallidum (SI/VP) pathway in fear extinction learning.
  • To compare the function of the IL→SI/VP pathway with the known IL→BLA pathway during extinction.
  • To elucidate the specific IL sub-pathways active during learning versus retrieval.

Main Methods:

  • Retrograde tracing to map IL projections to SI/VP and BLA in male mice.
  • Combined tracing with cFos expression to assess pathway activity during learning and retrieval.
  • In vitro electrophysiological recordings of IL neurons.
  • Optogenetic inactivation of the IL→SI/VP pathway.

Main Results:

  • IL projections to SI/VP originate from superficial (L2/3) and deep (L5) layers and are denser than IL→BLA projections.
  • L5 IL→SI/VP pathway shows increased activity during extinction learning; L2/3 IL→BLA pathway is active during retrieval.
  • IL→SI/VP neurons exhibit higher excitability during extinction learning compared to retrieval.
  • Inactivating the IL→SI/VP pathway enhances defensive freezing during extinction and re-extinction.

Conclusions:

  • The IL→SI/VP pathway is actively involved in fear extinction learning, where it functions to constrain defensive freezing.
  • The IL→BLA pathway is more involved in extinction memory retrieval.
  • The IL acts as a dynamic switchboard, modulating communication with SI/VP during learning and BLA during retrieval.