New Mechanisms Discovered in PTSD, Anxiety Disorders
A new physiologically based assay shows the role of neuropeptide Y in post-traumatic stress disorder and other anxiety disorders.
Researchers in a new study discovered how stress-induced anxiety can impact circuit function in the hippocampus. The study, published in The Journal of Neuroscience, closed a knowledge gap between the molecular, circuit, and behavioral effects of neuropeptide Y, a brain-signaling molecule.
These findings may lead to novel treatments that increase neuropeptide Y in patients with stress-induced anxiety disorders, such as post-traumatic stress disorder (PTSD).
High levels of neuropeptide Y are known to elicit anti-anxiety effects, but the levels of this molecule are diminished in patients with PTSD and anxiety disorders. The mechanisms behind how changing levels of neuropeptide Y impact circuit function to reduce or increase anxiety were previously unknown.
The researchers also discovered that exposing mice to a predator scent prevents the release of neuropeptide Y, which may increase anxiety, according to the study.
The US Department of Veterans Affairs has reported that 3.5% of the population has PTSD, and it affects 3 times more women than men. More than 10% of US military veterans who served in the Gulf War, Iraq, or Afghanistan have PTSD.
In the study, the investigators focused their efforts on the CA1 portion of the hippocampus, which is involved with learning and memory, and contains neurons that release neuropeptide Y.
The Schaffer collateral (SC) pathway and the temporoammonic (TA) pathway both activate CA1, and are involved with fear learning, according to the study. The TA neural pathway is known to be highly affected by stress.
The researchers sent electrical pulses through the SC and TA pathways to stimulate the release of neuropeptide Y from neurons through the use of a new physiologically based assay. This resulted in a change in plasticity of TA synapses onto excitatory neurons in the CA1. The release altered the plasticity of the SC synapses through the activation of both neural pathways.
The investigators also found that exposing mouse models of PTSD to predator scent inhibited the release of neuropeptide Y in the TA pathway, and changed the function of TA synapses, according to the study. This finding was significant because neuropeptide Y impairment causes circuit dysfunction in response to stress.
Due to these findings, in combination with previous findings, the investigators created a chain of events. The researchers hypothesize that predator scent impairs neuropeptide Y release, which enhances short-term plasticity of TA synapses. Enhanced plasticity then increases the strength of the neural pathway to spike CA1 nerve cells, which then alters the hippocampus function, and may increase the consolidation of fear learning, according to the study.
The authors also believe that this new assay could be used in other conditions where neuropeptide Y is inhibited, such as epilepsy, depression, and schizophrenia.
"Our study is the first demonstration of the impact of endogenously released neuropeptide Y on SC and TA short-term plasticity in response to stimulation with a physiologically derived spike train,” the authors wrote. “While no in vitro experiment completely duplicates in vivo conditions, these experiments bring us one step closer to the physiological situation and advance our understanding of how temporally complex activity regulates neuropeptide Y release from neuropeptide Y-positive interneurons."