Hippocampal--prefrontal BDNF and memory for fear extinction

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Molecular Psychiatry

Background:

• Fear extinction is a crucial learning process for overcoming phobias and trauma.
• The role of brain-derived neurotrophic factor (BDNF) in fear extinction circuits remains incompletely understood.
• Specific brain regions and their involvement in BDNF-mediated extinction require further elucidation.

Purpose of the Study:

• To investigate the necessity and sufficiency of BDNF in the infralimbic (IL) prefrontal cortex for fear extinction.
• To identify the brain circuits through which BDNF influences fear extinction.
• To determine if BDNF can modulate both recent and older fear memories.

Main Methods:

• Local pharmacological infusion of BDNF protein and anti-BDNF antibodies into the IL and prelimbic (PL) prefrontal cortex.
• Immunocytochemistry to assess BDNF levels in brain regions following extinction training.
• Electrophysiological recordings of IL and PL neuronal firing rates after BDNF infusion into the ventral hippocampus (vHPC).

Main Results:

• BDNF in the IL cortex, but not PL cortex, was both necessary and sufficient for fear extinction.
• BDNF infusion into the IL cortex induced extinction of both recent (1-day) and older (14-day) fear memories.
• Extinction training increased BDNF levels in the vHPC, with subsequent vHPC BDNF infusion enhancing IL neuron activity.

Conclusions:

• BDNF within the IL prefrontal cortex is a critical mediator of fear extinction.
• An extinction-induced increase in vHPC BDNF enhances IL neuronal excitability, facilitating the formation and maintenance of extinction memories.
• These findings highlight a novel vHPC-IL pathway involving BDNF in regulating fear memory.