Fear extinction requires infralimbic cortex projections to the basolateral amygdala

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Molecular Psychiatry

Background:

• Fear extinction, a process of forming new memories to suppress fear, is crucial for treating trauma-related disorders.
• The infralimbic prefrontal cortex (IL) and its projections to the basolateral amygdala (BLA) are known to be involved in fear extinction.
• The role of other IL targets, like the nucleus accumbens (NAc), in fear extinction remains less understood.

Purpose of the Study:

• To investigate the specific roles of IL-BLA and IL-NAc pathways in fear extinction memory.
• To determine if IL projections to the NAc are also involved in fear extinction.
• To establish a causal link between IL-BLA pathway activity and extinction retrieval.

Main Methods:

• Used electrophysiology and retrograde tracing in mice to analyze neuronal activity in IL and prelimbic cortex (PL) projections to BLA and NAc after fear extinction.
• Employed a pathway-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADD) strategy to selectively inhibit PFC-BLA neurons.
• Assessed the impact of inhibiting PFC-BLA neurons during extinction acquisition on subsequent extinction retrieval.

Main Results:

• Fear extinction increased the intrinsic excitability of IL-BLA projection neurons.
• Extinction appeared to reverse fear-induced changes in IL-NAc projection neurons.
• Chemogenetic inhibition of PFC-BLA neurons during extinction acquisition significantly impaired extinction retrieval.

Conclusions:

• The IL-BLA neural circuit plays a critical and causal role in the acquisition and retrieval of fear extinction memories.
• Findings clarify the specific contributions of IL projection pathways in fear extinction.
• This research provides insights into neural mechanisms underlying fear memory modification relevant to therapeutic interventions.