The Exciting Life of Inhibitory Neurons: Key Cells for Intelligence

The Context: The brain has two major types of neurons: excitatory neurons that fire to activate other neurons, and inhibitory neurons that restrain their fellow neurons. Inhibitory neurons are crucial for balance, rhythm, cognition, and computation, but we don’t know much about their life cycles or evolution, especially in primates.

The Study: A new study in Nature by scientists at the University of California, San Francisco led by NYSCF – Robertson Stem Cell Investigator Alex Pollen, PhD, discovers a new class of inhibitory neurons that only exists in primates. The team also found that primate brains send extra inhibitory neurons to areas involved in cognition – a process humans perhaps evolved as we relied more heavily on critical thinking.

The Importance: This study gives important insight into how our brains develop and how we have evolved to become uniquely human.

“[Inhibitory neurons] are crucial for intelligence, providing balance to excitatory neurons to prevent the brain from sliding into mass excitation like epilepsy,” noted graduate student Alex Schmitz, first author of the study in an article on Medium. “They also are the key to the computational processing units of the brain.”

“Beyond their function, their genesis is as exciting as the first moments of a sea turtle’s life: while most neurons of the brain are born right where they will live for the rest of their life, cerebral inhibitory neurons of each type are born in a specific zone, from which they migrate great distances to the many places they’re needed,” he added.

However, while some research has been done to understand how these inhibitory neurons are born, how they function, and why they have evolved the way they have, much of this research has taken place in mice. The team was interested in examining how inhibitory neurons behave in primate brains as opposed to mouse brains, to shed more light on the uniqueness of the human brain.

Monkey vs. Mouse

The team examined all the different types of inhibitory neurons that exist at six points during rhesus monkey brain development, and compared them to mice. They found two standout differences – the first involving a new type of inhibitory neuron.

“As soon as [inhibitory neurons] stop dividing [from stem cells] they immediately adopt one of a discrete number of ‘initial class’ identities,” noted Schmitz.

Most of the classes the researchers observed were similar to those found in mice; however, they discovered one type of inhibitory neuron – termed a TAC3 interneuron – that only exists in primates. Understanding more about the function of these inhibitory neurons in primate brains will help scientists gain a more comprehensive picture of brain development and inform strategies for making these cells from stem cells.

“Because TAC3+ striatal interneurons only exist in primates, it is difficult to ethically study them in living tissue,” wrote Schmitz. “This developmental snapshot can help future researchers figure out how these cells may be derived from stem cells in a dish so that they can be studied in more detail.”

Secondly, the team discovered that in primates, inhibitory neurons born in the olfactory bulb (a part of the brain that contributes to smell) migrate to the white matter and striatum (parts of the brain that control cognition). The team believes that primates have evolved this process because unlike a mouse, who requires an extra-keen sense of smell for finding food, it’s more important for primates to have critical thinking skills, so we send our inhibitory neurons to brain areas that focus on cognition.

“Primate decreased reliance on smell means they have a smaller olfactory bulb,” said Schmitz. “Meanwhile, [we have] an expanded cortex for thinking and generally being human. Perhaps the excess olfactory neurons without a home in the bulb go to the cortex to be “reused” in white matter!”

White matter in our frontal lobes is the latest maturing region of our brains, meaning that maybe these inhibitory neurons are sent there to help shape this especially plastic part of the brain.

Why Does it Matter?

All of these findings help us better understand why our brains develop the way they do, and illuminate how we have evolved to be such cognitively complex creatures. 

The team also stresses that the way these inhibitory neurons migrate may make them vulnerable to environmental influences, and this study lays the groundwork for understanding how they may become impacted by disease.