Healthcare (Commonwealth Union) – Scientists from the Salk Institute have developed new methods to study neuropeptides, the messenger proteins in the brain, and discovered that these proteins regulate the fear response in mice. This breakthrough could lead to the development of more effective painkillers and treatments for fear-related conditions such as PTSD (post-traumatic stress disorder) and anxiety.
Researchers of the study indicated that sensory signals move from the pain receptors in your finger, up through our spinal cord, and into your brainstem. There, a specific group of neurons transmits these pain signals to the amygdala, a higher brain region where they trigger an emotional fear response and help you remember to avoid hot skillets in the future. How the findings would translate in the human brain would be of interest.
This rapid translation of pain into a threat memory led scientists to believe it was mediated by fast-acting neurotransmitters. However, when Salk researchers explored the role of larger, slower-acting molecules called neuropeptides, they found that these were the main messengers in this fear circuit.
Neuropeptides are known to be crucial for brain communication, but their exact role has been unclear due to the lack of proper tools to study them in behaving animals. To uncover their role in this circuit, the Salk team developed two new tools that allow scientists to observe and manipulate neuropeptide release in the brains of live mice.
The study, appearing in Cell last month, revealed that the danger circuit primarily relies on neuropeptides, not fast neurotransmitters, and involves more than one neuropeptide. These findings could lead to the development of more effective painkillers or new treatments for fear-related conditions such as anxiety and PTSD.
“There is so much we have left to uncover about neuropeptides, but thankfully at Salk, we have the legacy of Nobel Prize winner Roger Guillemin’s work to highlight their importance and encourage our discovery,” explained the senior author Sung Han, associate professor and Pioneer Fund Development Chair at Salk. “To do this, we created two genetically encoded tools for monitoring and silencing neuropeptide release from nerve endings. We believe these new tools will significantly advance the field of neuropeptide research, and our discovery of their role in fear processing is really just the beginning.”
The researchers pointed out that to process and respond to our environment, information must move via our body and brain. This transmission occurs via neurons, which form organized circuits that direct information to its required destination. Neurons communicate by sending and receiving molecules such as neurotransmitters as well as neuropeptides.
Neuropeptides are generally considered neuromodulators that assist and modulate the function of primary neurotransmitters. However, early researchers like Roger Guillemin suggested that neuropeptides could act as primary transmitters themselves. This hypothesis hasn’t been thoroughly tested due to the lack of tools for visualizing and manipulating their release for behaving animals. The Salk team aimed to investigate neuropeptides to develop new tools for better understanding the part they play in brain circuits.
To specifically draw attention to neuropeptides, Han’s team utilized one of their unique features—while typical neurotransmitters are contained in small spheres called synaptic vesicles, neuropeptides are contained in large dense core vesicles. By engineering biochemical tools to target these large vesicles, they created neuropeptide sensor and silencer tools. The sensor tags large dense core vesicles with proteins that glow upon release from the nerve ending, allowing researchers to observe neuropeptide release in real-time. The silencer degrades neuropeptides within large dense core vesicles, revealing the effects without the neuropeptide in the brain.
“We have created a novel way to trace neuropeptide travel and function in the brains of living animals,” explained Dong-Il Kim, the first author of the study, who is also a postdoctoral researcher for Han’s lab. “These tools will help further our understanding of the brain’s neuropeptide circuits and enable neuroscientists to explore questions that were previously difficult to address.”
