Much of what we know about neurological and psychiatric disorders in humans can be traced back to fundamental studies of how animals, such as mice, learn and adapt to various situations. The study of behavioral responses has been illuminating, but this only tells part of the story.
The behaviors are often accompanied by physiological changes, such as increases in heart rate or fluctuations in body temperature, which may be indicative of an illness or a response to a drug. But this information has been nearly impossible to collect during behavioral tests on animals without being disturbing. Now, a new device could offer unprecedented insights into the underlying physiology that accompanies specific behaviors observed in mice.
With support from the NIBIB Small Business Programme, researchers have developed a battery-free wireless sensor that, when implanted in mice, was able to measure body temperature and heart and breathing rates along with behavioral information. A proof-of-concept study published in Neuron It reports a wide range of previously inaccessible physiological data taken during various behavioral tests, demonstrating the broad applicability of the instrument. The authors suggest that the device could open numerous avenues of research, such as the effects of brain disorders and treatments on sleep.
“The ability to combine physiology readouts along with behavior has the potential to significantly advance neuroscience and other fields of research,” said study co-author Cameron Good, Ph.D., director of research at NeuroLux, Inc. and consultant in animal surgery at Northwestern University.
Mouse-adapted technology
Measuring heart rate or monitoring body temperature may seem simple, but with traditional sensors, which require cables to transmit the data and batteries to power the device, retrieving data from small animals during behavioral tests has been a challenge.
The bulky equipment can induce anxiety in mice and restrict their movement, putting physiological data out of reach during tests in which the animals sleep, run, swim or interact with other mice.
Good, a neuroscientist by training, teamed up with John Rogers, Ph.D., professor of biomedical engineering at Northwestern University, to develop a solution. Together, the researchers designed and built a lightweight wireless device, small enough to be implanted under the skin of mice without obstructing movement or causing significant irritation.
To obtain energy, the device relies on a process called inductive coupling, where an external source transmits radio waves that generate an electrical current within the system. The device also features a wireless communication module commonly used in smart devices, allowing it to continuously transmit data to a computer.
The instrument houses a miniature temperature sensor and a high-performance accelerometer to detect vibrations in the body generated by different biological processes, such as heartbeat, breathing, and body movement. Because all of these processes can occur simultaneously, the system must differentiate the different types of vibrations.
“The saving grace here is that the vibrations associated with each activity cover a different range of frequencies. Cardiac cycles produce much spicier, high-frequency events than respiratory cycles,” said Rogers, a co-author of the study.
Because of these unique vibrational characteristics, researchers were able to develop machine learning algorithms to correlate different components of the raw data with specific sources. In addition to identifying breathing and heartbeats, the device could also distinguish physical activities, eliminating the need for researchers to manually document behavioral states while potentially watching hours of video recordings.
Exploring the possibilities
In the study, the authors implanted untethered devices in the abdomen of mice near the heart. To demonstrate some of the possible applications of their technology, they put mice through a wide spectrum of experiments. These included a swimming test commonly used in depression and anxiety studies, tests of motor function and cognition, as well as several social interaction studies.
Throughout the experiments, the device allowed the authors to obtain real-time physiological data and details that would have otherwise been inaccessible. For example, the team found that upon witnessing a physical conflict between two other mice, heart rates spiked in male mice but remained stable in females.
In another test, the authors used the device to automatically track both physiological data and behavioral states, including walking, resting, and grooming, while mice roamed freely around their enclosures for 17 days. The main implication of this experiment, Good explained, was the potential of their technology in sleep research, a field where physiological data in mice has been intensively sought to gain a better understanding of conditions such as sleep apnea.
Despite the promising findings of their study, the authors are working to expand the impact of this work.
“We’ve already shipped dozens of devices to people who have requested the technology for multi-animal studies, sleep-wake studies and other types that were previously impossible,” Rogers said.
In addition to neuroscience, researchers envision applications in cardiovascular research, drug development, and many other fields.
“This study is a great example of how scientists and engineers can bring unique but complementary skills to solve complex problems in biomedical research,” said Tiffani Lash, Ph.D., director of the NIBIB program in the Division of Health Informatics Technologies.
This research was partially supported by grants from NIBIB (R43EB033239) and the National Institute of Neurological Disorders and Stroke (1U01NS131406).
This prominent scientist describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is critical to promoting new and better ways to prevent, diagnose, and treat diseases. Science is an unpredictable and incremental process: each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without knowledge of fundamental basic research.
Study reference: Wei Ouyang et al. An implantable device for wireless monitoring of various physiobehavioral characteristics in small, freely behaving animals and in interacting groups. Neuron. DOI: 10.1016/j.neuron.2024.02.020
