Scientists Pick Apart a Fear Circuit in the Brain and Find a Molecular Target for Future Anti-Anxiety Treatments

Scientists Pick Apart a Fear Circuit in the Brain and Find a Molecular Target for Future Anti-Anxiety Treatments

Posted: January 26, 2015

Fear is a palpable thing to the millions of people who suffer from a variety of anxiety disorders, ranging from phobias to post-traumatic stress disorder (PTSD). But until very recently, fear has been an elusive thing for neuroscientists to track down in the living brain.

Last year, 2010 NARSAD Young Investigator grantee Bo Li, Ph.D., of Cold Spring Harbor Laboratory, N.Y., and colleagues, succeeded in pinpointing a place in an almond-shaped brain structure called the amygdala where groups of neurons are involved in the processes in which fear is learned and remembered. These neurons are located, they demonstrated, in the central amygdala. (We have two amygdalae, one in each brain hemisphere; they’re part of a single system.)

On January 19th, Dr. Li and his associates, including 2011 NARSAD Distinguished Investigator grantee Z. Josh Huang, reported in Nature they had taken their earlier discovery a major step forward. Through ingenious experiments performed in mice, they more fully fleshed out a fear pathway. Now they are able to say what drives neurons in the central amygdala to record and remember fearful things. The key orchestrator is a section of the thalamus, a central relay station that stands between incoming sensory information and the brain’s cerebral cortex – its incredibly sophisticated information processor.

A part of the thalamus called the PVT (paraventricular nucleus), already known to be sensitive to stress, acts as a sensor for tension – both physical and psychological. In their new research, Dr. Li’s team showed, in his words, that “the PVT is specifically activated when animals learn to fear, or when they recall fear memories.”  The team saw that neurons in the PVT extend tendrils deep into the central amygdala. And when the scientists experimentally interfered with those connecting links, animals were not able to learn to fear.

This fact suggests the PVT-amygdala connection would make a promising target for drugs to suppress the formation of fear memories. The question is: what exactly to target?  A potentially important clue discovered by Dr. Li’s team is a protein called BDNF. It’s well known to be a “neuroprotective” molecule – one that stimulates the birth of new neurons and enhances cell-to-cell connections in the brain.

Dr. Li has discovered that when BDNF is added to neurons in the central amygdala, they are stimulated, triggering a fear response in animals that haven’t even been exposed to a fearful stimulus. BDNF also promoted the formation of long-term fear memories in these animals. “BDNF is the chemical messenger that allows the PVT to exert control over the central amygdala,” Dr. Li concludes. “This makes it a target in future treatment approaches for anxiety disorders.”

Read the paper abstract.

Monday, January 26, 2015

Fear is a palpable thing to the millions of people who suffer from a variety of anxiety disorders, ranging from phobias to post-traumatic stress disorder (PTSD). But until very recently, fear has been an elusive thing for neuroscientists to track down in the living brain.

Last year, 2010 NARSAD Young Investigator grantee Bo Li, Ph.D., of Cold Spring Harbor Laboratory, N.Y., and colleagues, succeeded in pinpointing a place in an almond-shaped brain structure called the amygdala where groups of neurons are involved in the processes in which fear is learned and remembered. These neurons are located, they demonstrated, in the central amygdala. (We have two amygdalae, one in each brain hemisphere; they’re part of a single system.)

On January 19th, Dr. Li and his associates, including 2011 NARSAD Distinguished Investigator grantee Z. Josh Huang, reported in Nature they had taken their earlier discovery a major step forward. Through ingenious experiments performed in mice, they more fully fleshed out a fear pathway. Now they are able to say what drives neurons in the central amygdala to record and remember fearful things. The key orchestrator is a section of the thalamus, a central relay station that stands between incoming sensory information and the brain’s cerebral cortex – its incredibly sophisticated information processor.

A part of the thalamus called the PVT (paraventricular nucleus), already known to be sensitive to stress, acts as a sensor for tension – both physical and psychological. In their new research, Dr. Li’s team showed, in his words, that “the PVT is specifically activated when animals learn to fear, or when they recall fear memories.”  The team saw that neurons in the PVT extend tendrils deep into the central amygdala. And when the scientists experimentally interfered with those connecting links, animals were not able to learn to fear.

This fact suggests the PVT-amygdala connection would make a promising target for drugs to suppress the formation of fear memories. The question is: what exactly to target?  A potentially important clue discovered by Dr. Li’s team is a protein called BDNF. It’s well known to be a “neuroprotective” molecule – one that stimulates the birth of new neurons and enhances cell-to-cell connections in the brain.

Dr. Li has discovered that when BDNF is added to neurons in the central amygdala, they are stimulated, triggering a fear response in animals that haven’t even been exposed to a fearful stimulus. BDNF also promoted the formation of long-term fear memories in these animals. “BDNF is the chemical messenger that allows the PVT to exert control over the central amygdala,” Dr. Li concludes. “This makes it a target in future treatment approaches for anxiety disorders.”

Read the paper abstract.