Researchers identify the best methods to study resting brain states in marmosets

Researchers identify the best methods to study resting brain states in marmosets

A team led by researchers at Tokyo Metropolitan University has identified the best methods to study the resting state of marmoset brains using functional MRI. Studies often use sedatives and anesthetics to limit movement during measurements, but the drugs themselves can affect brain activity. The team examined seven medications and identified options that preserved normal function while minimizing movement. Their work expands the research framework for an important model organism.

Model organisms are species that scientists study to understand certain aspects of biology that may apply to other organisms. Examples include a wide range of sizes and species, from baker's yeast and fruit flies to guinea pigs. Recently, the common marmoset, a small primate originally from South America, has attracted considerable interest, particularly in the neurological sciences. Despite their tiny body size, they retain the highly developed brain structure of primates, making it possible to conduct studies that can shed light on how our own brains work and how we can overcome diseases that affect higher brain function.

An important line of research is the use of functional MRI (fMRI) to study marmoset brains at rest. fMRI is a non-invasive imaging technique that can image blood flow in the body; in the brain this may be associated with localized activity. This provides a unique insight into the Resting State Network (RSN), an important network of connections between different parts of the brain. However, studying marmosets in an fMRI machine requires limitations; this in turn requires sedatives/anesthetics to minimize distress to the animals. The drugs themselves can interfere with brain activity and limit the scope of findings.

Therefore, a team of researchers led by Associate Professor Junichi Hata set out to examine drugs that have the least impact on the RSN. They tested seven common sedatives and anesthetics, compared the animal's RSN while awake and while on medication, and tracked head movements, which in turn can affect the quality of the data. They found that the drugs midazolam (Mida) and dexmedetomidine (Dex) preserved the network best, but left some traces of head movement. Three of the remaining five, Alfaxalone (Alfa), Isoflurane (Iso) and Sevoflurane (Sevo), were found to have a significant impact on brain function, but the final two, Propofol (Propo) and a combination of Isoflurane and Dexmedetomidine (IsoDex), preserved enough of the RSN while keeping movement minimal. The team concluded that midazolam or dexmedetomidine combined with mild restraint may be the most realistic solution to obtain the most accurate data, but if restraint is difficult, either propofol or the isoflurane/dexmedetomidine combination should be used.

Although studies on proper dosage and its effects on brain function are still in progress, these results provide clear direction on how future marmoset studies should be conducted. Better data will mean exciting new advances in understanding high-level brain function and related pathologies.

This work was supported by the Program for Brain Mapping by Integrated Neurotechnologies for Disease Studies from the Japan Agency for Medical Research and Development (Grant Number JP21dm0207001), a KAKENHI Grant-in-Aid from the Japan Society for the Promotion of Science (Grant Number JP20H03630), and the “MRI Platform”, a program of the Project for Promoting Public Use of Advanced Research Infrastructure of the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant Number JPMXS0450400622).

Source:

Tokyo Metropolitan University

Reference:

Muta, K., et al. (2022) Effects of sedatives or anesthetics on measuring resting brain function in marmosets. Cerebral cortex. doi.org/10.1093/cercor/bhac406.

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