Hippocampal Inputs in the Prelimbic Cortex Curb Fear after Extinction

Area of Science:

• Neuroscience
• Behavioral Science
• Memory Research

Background:

• Fear memories are easily formed, but extinction requires extensive training.
• The prelimbic cortex (PL) integrates fear signals and is crucial for memory retrieval.
• The role of ventral hippocampus (vHIP) and basolateral amygdala (BL) inputs to the PL in fear extinction is unclear.

Purpose of the Study:

• To investigate how vHIP and BL inputs to the PL regulate fear display after extinction.
• To identify neuronal populations in the PL associated with fear extinction and relapse.
• To explore the impact of fear extinction training duration on vHIP-PL pathway connectivity.

Main Methods:

• Functional anatomy tracing in male rats.
• Optogenetic stimulation of the vHIP-PL pathway.
• Analysis of neuronal activity in the PL during fear retrieval and extinction recall.

Main Results:

• Two distinct neuronal subpopulations in the PL were identified, linked to successful extinction or fear relapse.
• vHIP input dominated PL activity during fear extinction memory retrieval.
• BL input was greater during fear memory retrieval, irrespective of memory age or context.
• Optogenetic stimulation effects on fear varied with extinction training duration and time post-extinction.

Conclusions:

• Repeated fear extinction training gradually modifies vHIP-PL connectivity, enabling fear suppression.
• Inadequate fear suppression allows BL signals to dominate, leading to heightened fear.
• Extinction memory fading is linked to transient changes in vHIP-PL connectivity, posing a challenge for long-term fear suppression in therapies.