Researchers at the University of Chicago have overcome technical challenges to record neural activity of marmosets, a model system in neuroscience, during natural behavior. The new methodology involved a modular wireless headpiece that avoids common pitfalls in neurophysiological recordings, such as restraint and head immobilization, and allowed researchers to observe the marmosets’ neural activity in multiple behavioral states, over multiple years.

The innovation, published on July 13 in Cell Reports, promotes the long-term health of the animal and offers scientists flexibility in the duration and focus of their experiments. For the marmoset, a small primate model system for motor activity, the approach enables them to move freely and with minimal handling, which could shed light on the neural control of movement in their natural behavioral repertoire. Understanding how marmosets control their natural movements can provide insights into human motor control, which has implications for conditions such as Parkinson’s Disease and the development of brain computer interfaces to restore lost motor function.

“A model organism should be exceptional at doing some behavior, and marmosets are exceptional at movement,” said lead author Jeffrey Walker, PhD, a postdoctoral fellow in the Hatsopoulos Lab at UChicago. “They move through trees with such fluency, it’s clear they have remarkable capacities for voluntary movement and bodily coordination. It is very likely that there are adaptations in the marmoset’s nervous system that have evolved to allow for that exceptional behavior.”

To understand the need for the new methodology, it is useful to compare marmoset studies to those of different animals. Neurosurgical techniques that promote the long-term health of the animal have been available to other primate species such as the rhesus macaque and humans, but they had never been applied to marmosets.

The first task was to make surgery amenable to the long-term health of the marmoset. The cranial anatomy of the marmoset constrained the size and design of the hardware, and careful attention was required. The researchers adapted techniques from human neurosurgery, such as custom-fit orthopedic implants, and applied them to the marmoset. The result of the surgery was a 96-channel electrode array connected to the sensorimotor cortex, which was secured with a custom-fit titanium pedestal and hydroxyapatite, a material to promote biocompatiblity. As a result of the improved neurosurgery, the researchers were able to record neural activity in individual marmosets for multiple years. “We want a healthy, happy marmoset in order to record with them for a long period of time,” said Walker.

The next challenge was to design the hardware in such a way that the researchers would need to handle the animal as little as possible. A 3D-printed helmet served to both protect the surgical site and act as a stage for the wireless recording device and a battery. The battery had to be small, but fortunately it was designed such that it could easily snap on and off the helmet set-up for recharging, without picking up the marmoset as it rested in a hammock. Avoiding excessive handling further allowed the marmosets to move and behave as naturally as possible, providing cleaner, more useful data.

“In science in general, when you want to measure a system, you have to perturb that system in some way; ideally, you can minimize that perturbation,” said Walker. “In a three-month period, we were able to record near daily, multiple times a day, and in that time I only had to pick up the marmoset three times.”

With the hardware established, the researchers were able to record sensorimotor cortical neuron populations from two marmosets during activities such as foraging, leaping, sitting, and sleeping, for up to three years each. The marmosets remained happy and healthy throughout the experiment, and when the electrode arrays began to fail, as it became harder to record neuronal activity, the researchers were able to simply replace the arrays with a new one, rather than end the experiments.

The researchers claim their approach can be adapted to other brain areas, and perhaps other neural recording technologies. The new methodology will allow researchers to study neural circuit functions during natural behaviors, including social behaviors and sleep, in a minimally disruptive way and in settings that more closely resemble the animal’s natural environment. Collecting data about natural movement behaviors will, in turn, clarify the neural mechanisms of movement, information that is important for understanding and treating movement disorders.

By Matt Reyer, PhD

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