University Of Texas At Dallas Researchers Develop Tech For Understanding Brain Circuits, Behavior

Chemical messengers in the brain called neuropeptides influence nearly every function in the human body, yet scientific understanding of the molecules is limited because of a lack of methods to study them.

University of Texas at Dallas researchers and collaborators at other institutions have developed two new tools that make it possible for the first time to control the release of neuropeptides in a mouse brain, as well as track the molecules, study their action on brain circuits and examine how they affect behavior in real time.

Led by Dr. Zhenpeng Qin, associate professor of mechanical engineering and Fellow, Eugene McDermott Professor in the Erik Jonsson School of Engineering and Computer Science, the researchers demonstrated the tool that controls neuropeptide release in a paper published in the January 2023 print edition of Nano Research. A study on a second tool, which allows scientists to monitor neuropeptides better after they are released, was published in the Aug. 22, 2022, print edition of Angewandte Chemie, a journal of the German Chemical Society.

Neuropeptides are molecules that are produced and released by nerve cells. As they diffuse through tissue, they bind to different cell types and are key to modulating many body functions and behavior, ranging from heart rate and muscle movement to maternal behavior.

Neuropeptides send information broadly, like a Wi-Fi signal, rather than directly from one cell to another, which has made it challenging to determine their impact, said Qin, a co-corresponding author of both studies.

The researchers’ goal is to help scientists solve questions that can lead to better treatments for a range of brain diseases.

“Our new tools for the first time allow scientists to modulate neuropeptides, which is critical for understanding how they work in the brain,” Qin said. “We hope that, ultimately, these tools can facilitate research that leads to better treatments for patients.”

The methods build on Qin’s previous work with microscopic capsules called nanovesicles. The tool to control the release of neuropeptides involves packaging the molecules in a gold-coated nanovesicle, which is implanted in the brain. Researchers control the process using pulses of laser light, which activate the gold coating and cause the nanovesicle to release its contents.

The method they developed to track a neuropeptide’s activity involves the use of specially cultured cells and two fluorescent proteins. Dubbed Cell-based Neurotransmitter Fluorescent-Engineered Reporters, or CNiFERS (pronounced “sniffers”), these cells are engineered to express fluorescent proteins as well as a specific receptor that binds to neuropeptides. Stimulation by light activates the fluorescent proteins in a cell, which lights up if a neuropeptide has attached to the receptor. The tool can detect both the presence and concentration of neuropeptides.

“We hope that, ultimately, these tools can facilitate research that leads to better treatments for patients.”

Dr. Zhenpeng Qin, associate professor of mechanical engineering in the Erik Jonsson School of Engineering and Computer Science

“We want to know how far a neuropeptide signal can diffuse. We are also trying to find out how much time it takes to reach other cells,” said Dr. Hejian Xiong, mechanical engineering research scientist and first author of both studies.

These studies were supported by the National Science Foundation, the National Institute of Neurological Disorders and Stroke (RF1NS110499), the International Human Frontier Science Program, and the Phospholipid Research Center in Heidelberg, Germany. The Angewandte Chemie study also received support from the National Institute of Mental Health (RO1MH111499).

Other UT Dallas co-authors of the Nano Research study included Kevin A. Alberto, a chemistry doctoral student; Jonghae Youn PhD’19, now a scientist at SCIEX; Dr. Xiuying Li, a former UTD research scientist now at Immorna; Yang Wang PhD’20; and Dr. Steven Nielsen, a co-corresponding author and associate professor of chemistry in the School of Natural Sciences and Mathematics.

UT Dallas co-authors of the Angewandte Chemie study included Dr. Hui Ouyang, assistant professor of mechanical engineering; Xueqi Xu, mechanical engineering doctoral student; Chen Xie, mechanical engineering doctoral student; Blake A. Wilson PhD’16, research associate in mechanical engineering; Krutin Kumar BS’21, now a business development analyst at Scripps Research; and Li and Youn.

The work was done in collaboration with researchers at other institutions, including Dr. Paul Slesinger, a co-corresponding author of both studies and director of the Center for Neurotechnology and Behavior at the Icahn School of Medicine at Mount Sinai. In addition to Mount Sinai, other institutions with co-authors of either paper included New York University, SUNY Downstate Health Sciences University, University of Minnesota and University of California, San Diego.