New Study Targets Role of Specific Neurons in Fear Behaviors

October 25, 2016

In a recently published paper, Kerry J. Ressler, MD, PhD, chief scientific officer for McLean Hospital and professor of Psychiatry at Harvard Medical School, and Kenneth M. McCullough describe their novel method for evaluating how a specific group of neurons within the amygdala—a mass of cells located deep within the brain—directly inhibits fear behaviors.

“It has become increasingly clear that we need to drill down to the cellular level in order to better understand the complexity and functionality of the brain,” said Ressler. “However, getting to that level, particularly as it relates to the role of specific types of cells in specific types of functional circuits, has been a struggle for many years in the field of cellular neurobiology. We believe that this current research is an important advance toward making cellular analysis in the brain more accessible.”

McLean research
Dr. Ressler’s Neurobiology of Fear Laboratory investigates the mechanisms underlying fear processes

Ressler, McCullough, and their colleagues set out to determine the role of one specific neuron group within the amygdala. They used a genetically modified animal model that facilitated the targeting of a specific neural cell population characterized by the presence of Thy1 protein. They first demonstrated that these particular cells within the amygdala automatically inhibit the fear response as well as enhance the learned inhibition process. They then identified the genetic pathways that distinguish these cells. Specifically, they showed that the activation of receptors that are primarily characteristic of this neural cell type, such as the neurotensin type 2 receptor, could directly inhibit fear.

Building evidence shows that the amygdala’s neural circuit is a direct driver of different emotional responses that underlie a variety of psychiatric disorders in humans, including PTSD, addiction, and depression. And all of these fear-related conditions are thought to result primarily from the inability to inhibit the innate fear response. Through novel methods such as that used in this current study, investigators hope to move on to identify new cell-specific drug approaches that inhibit the pathological fear responses at the core of so many psychiatric conditions.

Learn more about the study in Nature Communications.

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