LSU Health New Orleans Study Identifies a Potential New Approach to PTSD Treatment

September 13, 2023

An LSU Health New Orleans research study led by Siqiong June Liu, PhD, Professor of Cell Biology and Anatomy, has found that cerebellar inhibitory interneurons are essential for fear memory, a type of emotional memory formation. Inhibitory interneurons within the cerebellar circuitry act as gatekeepers and control the output of the cerebellar cortex. The formation of fear memory requires the activity of these interneurons. The findings, which may lead to a novel treatment approach for post-traumatic stress disorder, are published in Cell Reports, available here.

“While synaptic plasticity is considered the basis of learning and memory, modifications of the intrinsic excitability of neurons can amplify the output of neuronal circuits and consequently change behavior,” notes Dr. Liu. “In the cerebellum, we find that silencing molecular layer interneurons completely abolishes fear memory, revealing their critical role in memory consolidation.”

The cerebellum is a brain region that is known to control motor coordination. Recent work has shown that it is also critical for the formation of memory, but not how the cerebellar circuitry accomplishes this function.

The research team found that fear conditioning suppresses hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and enhances cerebellar interneuron excitability. HCN currents are similar to pacemakers in the brain because they help regulate rhythmic activity and communication between brain cells. HCN loss is driven by a learning-induced decrease in endocannabinoid levels. When the activity of these neurons is suppressed, experimental animals do not remember the experience a few hours after learning.

“Our study reveals that activity in cerebellar interneurons drives fear memory formation via a learning-specific increase in intrinsic excitability,” Liu concludes. “This highlights the importance of moving beyond traditional synaptic plasticity-focused investigations of memory formation and suggests a novel therapeutic approach for the treatment of PTSD.”

LSU Health New Orleans co-authors of the paper include Drs. Kathryn Lynn Carzoli, Georgios Kogias and Jessica Fawcett-Patel. Drs. Liu, Kogias and Fawcett-Patel are also affiliated with the Southeast Louisiana VA Healthcare System, New Orleans.

The research was supported by grants from the National Institutes of Health, The Brown Foundation and the Department of Veterans Affairs.

______________________________________________________________________________________________________________ LSU Health Sciences Center New Orleans (LSU Health New Orleans) educates Louisiana's health care professionals. The state's health sciences university leader, LSU Health New Orleans includes a School of Medicine with campuses in Baton Rouge and Lafayette, the state's only School of Dentistry, Louisiana's only public School of Public Health, and Schools of Allied Health Professions, Nursing, and Graduate Studies. LSU Health New Orleans faculty take care of patients in public and private hospitals and clinics throughout the region. In the vanguard of biosciences research, the LSU Health New Orleans research enterprise generates jobs and enormous annual economic impact. LSU Health New Orleans faculty have made lifesaving discoveries and continue to work to prevent, advance treatment or cure disease. To learn more, visit http://www.lsuhsc.edu, http://www.twitter.com/LSUHealthNO, or http://www.facebook.com/LSUHSC.

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