# The role of cerebellar endocannabinoids in the reconsolidation and extinction of fear memory

> **NIH VA I01** · SOUTHEAST LOUISIANA VETERANS HEALTH CARE · 2024 · —

## Abstract

One debilitating mental health problem among veterans is post-traumatic stress disorder
(PTSD), which is an anxiety disorder and develops following the experience of life-threatening
psychological trauma. A central feature of PTSD is a persistent, pervasive fear response after
the threat is no longer present. This is caused by a failure to extinguish the fear memory, a
process that involves learning that the stimulus is no longer associated with the aversive events.
This is a form of inhibitory learning and produces a lasting decrease in the conditioned fear
response (“extinction memory”). Extensive research has been conducted on
the
amygdala
and medial prefrontal cortex (mPFC)
.
The knowledge gained from these studies has enabled
the development of psychotherapeutic interventions that aim to attenuate fear memory by
enhancing extinction. However nearly half of the patients do not respond to exposure therapy.
This failure highlights the need to move beyond a traditional amygdala- and mPFC-focused
investigation of extinction. The second approach is to disrupt the reconsolidation process.
Consolidated memory can become transiently labile following reactivation trials and undergoes
a reconsolidation process that re-stabilizes the fear memory. During this short window, memory
can be disrupted. This offers a window of opportunity for reduce the original fear memory with
amnestic agents as a treatment for PTSD. The cerebellum regulates emotional behavior
and forms extensive reciprocal connections with cortical regions, including PFC. It is critically
involved in both the consolidation and reconsolidation of fear memory. Our preliminary results
show that inhibition of cerebellar Purkinje cell activity impaired extinction memory. We will test
the hypotheses that reactivation reduces endocannabinoid signaling in the cerebellum to
restabilize memory in Aim 1. Aim 2 will test whether extinction increases endocannabinoid
signaling in the cerebellum and this is required for extinction memory. We will determine
whether inhibition of a transcription factor that regulates an endocannabinoid degrading enzyme
disrupts the reconsolidation of fear memory and facilitates extinction memory. Because the
proposed study investigates a new mechanism underlying the regulation of endocannabinoid
metabolism by reactivation and extinction, it could suggest a novel treatment strategy for PTSD
and a new therapeutic target.

## Key facts

- **NIH application ID:** 10590147
- **Project number:** 1I01BX006043-01A1
- **Recipient organization:** SOUTHEAST LOUISIANA VETERANS HEALTH CARE
- **Principal Investigator:** Siqiong June Liu
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-10-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10590147

## Citation

> US National Institutes of Health, RePORTER application 10590147, The role of cerebellar endocannabinoids in the reconsolidation and extinction of fear memory (1I01BX006043-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10590147. Licensed CC0.

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