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Prefrontal control of the amygdala
Ekaterina Likhtik1, Joe Guillaume Pelletier, Rony Paz
1Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, New Jersey 07102, USA.
Summary
Fear extinction failure underlies anxiety disorders. This study found medial prefrontal cortex (mPFC) excites basolateral amygdala (BLA) neurons, suggesting fear memory inhibition is gated downstream of BLA, not directly from mPFC projections.
Area of Science:
- Neuroscience
- Psychiatry
- Behavioral Science
Background:
- Anxiety disorders are linked to impaired fear memory extinction.
- Fear extinction relies on medial prefrontal cortex (mPFC) projections to the amygdala.
- The mechanism of mPFC-driven fear inhibition in the central medial amygdala (CEm) remains unclear.
Purpose of the Study:
- Investigate the indirect pathway of mPFC-evoked inhibition of CEm neurons.
- Determine if mPFC inhibits CEm via feedforward inhibition of basolateral amygdala (BLA) neurons.
- Elucidate the neural circuitry underlying fear extinction.
Main Methods:
- Electrophysiological recordings in rodents.
- In vivo and ex vivo brain slice preparations.
- Optogenetic and chemogenetic manipulations.
Main Results:
- Contrary to hypotheses, mPFC inputs were found to excite BLA neurons.
- This excitation suggests a novel gating mechanism downstream of the BLA.
- The direct mPFC projections to CEm output neurons are sparse.
Conclusions:
- The mPFC-induced inhibition of CEm fear pathways is not mediated by feedforward inhibition of BLA neurons.
- Fear memory extinction involves an active gating mechanism downstream of the BLA.
- This finding offers new insights into the neural basis of anxiety disorders.