Denis Paré

Identifying the Cells that Can Break the Fear Cycle

Pool of cells in the brain's amygdala could help to treat anxiety disorders

Fear is an emotion that motivates us to avoid danger, but if prolonged can also lead to anxiety disorders and a destructive cycle of avoidance behaviors. In his lab, neuroscientist Denis Paré has identified a population of cells in a structure of the brain called the amygdala that could be a target for drugs to treat anxiety disorders.

According to the National Institute of Mental Health, nearly 40 million American adults each year experience an anxiety disorder. These include such debilitating conditions as phobias, panic disorders and post-traumatic stress disorder (PTSD). Left untreated, anxiety disorders can lead to myriad problems that hinder daily life and ones that can ruin it altogether, such as drug abuse, alcoholism, unemployment, marital problems and suicide.

Functional imaging studies in combat veterans have revealed that the amygdala, a cerebral structure of the temporal lobe known to play a key role in fear and anxiety, is hyperactive in PTSD subjects. Turns out that the amygdala, however, also contains a population of cells that if properly stimulated could potentially eliminate fear memories and reduce anxiety. As reported in the July 31, 2008 issue of Nature, Paré, professor at the Center for Molecular and Behavioral Neuroscience at Rutgers University in Newark, has identified a critical component of the amygdala’s neural network that allows extinction, or the inhibition, of fear memories to take place.

"It has been found that people with anxiety disorders exhibit an extinction deficit, or an inability to 'forget' fearful events," notes Paré. Until recently, the mechanisms that allow extinction to happen have remained unclear. But Paré’s research has identified a cluster of amygdala cells, the intercalated (ITC) neurons, which play a key role in the process of extinction.

His findings show that ITC cells inhibit amygdala outputs to the brainstem structures that generate fear responses. When those ITC cells are destroyed with a targeted toxin in rats, extinction memory is impeded, mimicking the behavior seen in PTSD. Conversely, if pharmacological interventions can be developed to enhance the excitability of ITC cells, it then may become possible to facilitate extinction.

'Our hope is that as we gain an even deeper understanding of the acquisition and extinction of conditioned fear that it will lead to better treatment of anxiety disorders," says Paré.

In his related research, Paré is investigating how the amygdala modulates memory in emotionally charged situations and mapping the intrinsic circuitry of the amygdala. His research is supported by grants from the National Institute of Mental Health.


Biography

Denis Paré, a native of Canada, earned his PhD in Neurobiology from the Université Laval (Quebec) in 1990. He then performed a post-doctoral internship with Rodolfo Llinas at New York University, and later accepted an assistant professor position with the Physiology Department of the Faculty of Medicine at Université Laval. In 1992, he was presented with the Young Investigator Award from the Swiss Medical Research Foundation. He joined Rutgers University in Newark in 2002 as professor of neuroscience with the Center for Molecular and Behavioral Neuroscience. He is a member of the editorial boards of the Journal of Neurophysiology, Neuroscience, and the Journal of Neuroscience, and serves as a reviewer for numerous other scientific journals, including Science, Nature, and Nature-Neuroscience.


Selected Publications


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