Post-Traumatic Stress Disorder (PTSD) is an anxiety-based disorder that can develop after a person is involved in or has witnessed traumatic events. The main treatment for people with PTSD are counseling and medication, however, non-specific SSRI antidepressants for PTSD are shown to only benefit 50% of sufferers, with it still unclear if using medications and counseling together produces better outcomes. Now, a study from researchers at Texas A&M University identifies an area in the brain involved in inhibiting fear, a discovery that holds potential for clinical interventions in patients with psychiatric diseases such as PTSD. The team states they have discovered a small brain region in the thalamus, called the nucleus reuniens, plays a role in inhibiting fear in rats. The opensource study is published in the journal Nature Communications.
Previous studies show most drugs prescribed by physicians to treat psychiatric disorders are indiscriminate and target all neurons in the brain. Behavioral therapies, such as extinction therapy for PTSD where patients undergo prolonged, repetitive exposure to their traumas in safe settings, are effective in diminishing fear, however, patients often relapse. The current study provides a specific target for fear suppression by showing that prefrontal cortex inputs to the nucleus reuniens are critically involved in fear extinction.
The current study exposes rats to tones paired initially with mild foot shocks to create the fear response. An extinction procedure is then used which involves exposing the rats to the tones repetitively for prolonged periods to suppress the fear. Results show that by using a pharmacological approach to inactivate the nucleus reuniens, the rats were unable to suppress fear. The lab then used a targeted pharmacogenetic strategy to silence neurons selectively in the prefrontal cortex projecting to the reuniens. Data findings show engineered viruses carrying pharmaceutically-activated designer receptors inhibited these inputs and prevented rats from suppressing fear.
The group explains the nucleus reuniens receives inputs from the prefrontal cortex, interconnecting the prefrontal cortex and hippocampus, and may serve in a pivotal role in regulating emotional-based learning and memory. They go on to add as the prefrontal cortex plays a role in regulating emotions, identifying the projection from the prefrontal cortex to the nucleus reuniens in the thalamus points to parts of the brain important for inhibiting fear. They conclude this could be an avenue to new drugs, therapies, and interventions for psychiatric disorders.
The team surmises their data shows the nucleus reuniens and its prefrontal cortex inputs are critical for the extinction of Pavlovian-based fear in rats. For the future, the researchers state by identifying the involvement of this specific circuit of the brain in fear inhibition, the global medical community can now investigate more targeted treatments for anxiety-based disorders that work better and last longer.
Source: Texas A&M University
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