From Rats to Monkeys to Humans: The Hope of Treating Anxiety and Depression

The brains of monkeys and mice could hold answers about how to best treat common human mental health illnesses such as anxiety and depression.

Research with laboratory animals helps scientists understand how the brain works and in turn improve therapies for individuals left with symptoms that interfere with daily life.

Imaging of human brain activity has connected the frontal regions of the cerebral cortex to anxiety and depression. Patients with damage in these regions of the brain, and particularly in the brain’s ventromedial prefrontal cortex (vmPFC), show a range of behavioral abnormalities in their social interactions, decision making, personality, emotions and memory.

Studies with rats and mice in early efforts to understand what goes wrong in patients with these mental health disorders found that the vmPFC is involved in regulating responses to both rewards and threats. Therefore, scientists focused on this region of the brain to gain a better understanding of anxiety and depression in humans, but there is a problem.

Rodents do not have the same prefrontal regions of cerebral cortex as humans. There are at least four types of structural organization in the prefrontal cortex of mammals: granular, dysgranular and agranular areas and the allocortex. These distinct areal organizations almost certainly serve different functions.

There is a striking difference between human and rat ventromedial prefrontal cortices (vmPFCs) in Figure 1 below. The human vmPFC shows a large granular area, smaller dysgranular and agranular areas and a very small allocortex. The rat vmPFC by contrast is primarily agranular with a larger allocortex than that of humans.

The rat vmPFC relates to behavior much like the human vmPFC, but is it the same behavior? Another question to consider: How do granular, dysgranular and agranular regions of vmPFC relate to the predominantly agranular area of the rat vmPFC?

Fortunately, the relationship of the animal to the human brain need not depend only on human and rat comparisons. In recent years scientists have turned their attention to nonhuman primates to study the vmPFC due to its anatomical and functional similarities to that of humans.

The marmoset, which is a New World monkey species, has a vmPFC with large granular and dygranular areas in Figure 1, much like the human vmPFC and unlike the rat vmPFC. The predominance of granular and dysgranular vmPFC in a macaque monkey, an Old Word monkey species, is even greater than in the marmoset and even closer to the human vmPFC.

The functional relationship of caudal agranularregions of the marmoset vmPFC to similar regions in a human appears more comparable than to those of a rat. Thus, monkeys play an important part in reducing a gap between studies with humans and rodents. (ALSO READ: Deep Brain Stimulation Offers Parkinson’s Patients New Hope)

However, ultimately, integrating findings from studies with both rodents and monkeys will help facilitate understanding of debilitating disorders and develop better treatments for illnesses that include anxiety and depression.

There is hope to further unlock medical mysteries.

This article is based on: Why we need nonhuman primates to study the role of ventromedial prefrontal cortex in the regulation of threat- and reward-elicited responses. Angela C. Roberts and Hannah F. Clarke. Proceedings of the National Academy of Science USA 2019 Dec 26;116(52)26297-26305.

Guiding Scientist: Robert H. Wurtz, PhD, distinguished investigator emeritus at the NIH’s National Eye Institute. Dr. Wurtz has served as president of the Society for Neuroscience and has been elected to the National Academy of Sciences, National Academy of Medicine, and American Academy of Arts and Sciences.

This article was vetted by professor Angela Roberts, Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom.