Researchers discover new brain circuit, crucial for learning new motor skills

From playing the piano to riding a bike, life without them is hard to imagine. But how does the brain do it? A new study has shed light on a newly discovered circuit in the brain that could give us this remarkable ability.

The study was published in the journal Science Advances.

The cortex forms the outer layer of our brain and is the ultimate multitasker, involved in everything from language and cognition to memory and voluntary actions. It is actually used to read that exact sentence of yours. But it doesn't act alone and makes extensive connections to many other brain regions.

“We were particularly interested in two main types of cells in the cortex known as IT (intratelencephalic) and PT (pyramidal tract) neurons,” said Nicolas Morgenstern, the first author of this study, which was being developed in the group then led by Rui Costa, at the Champalimaud Foundation, in Lisbon, Portugal.

“Both IT and PT cells send signals from the cortex to another area buried deeper in the brain called the striatum. These ‘cortico-striatal’ connections (ie connections from the cortex to the striatum) are very important for motor learning and have been linked to movement disorders such as Parkinson’s disease.”

This is where the third main character of the story emerged: the spiny projection neurons (SPNs), which made up 95 percent of the neurons in the striatum. SPNs are directly contacted by both IT and PT cells. “We wanted to understand the different roles of IT and PT cells in this brain circuitry that is so important for motor learning and behavior.” To better understand these corticostriatal relationships, the authors used a technique that is present in (almost) every neuroscientist’s tool kit: optogenetics, a method of controlling the activity of cells with light. As Morgenstern explained, “We have genetically engineered either IT or PT cells in mice, which allows us to independently activate these cell types using optogenetics and measure their differential effects on SPNs in the striatum.” Using this approach, the authors discovered a new corticostriatal signaling pathway when recording the activity of neurons in vitro. Along this pathway, a fourth major player emerged: striatal cholinergic interneurons (ChIs). ChIs in the striatum, acting as the “middleman” in a three-person squadron, receive input from PT cells and in turn excite SPNs. “We found that PT cells preferentially connect to ChIs that indirectly activate SPNs,” says Morgenstern.

Using pharmacological methods, the authors were able to show exactly how ChIs stimulate SPNs. When activated by PT neurons, ChIs release a neurotransmitter called acetylcholine (ACh). Neurotransmitters are chemical messengers that carry signals from one cell to another. When ChIs release ACh, they cause the nerve fibers of nearby cells to excite SPNs.

These results show that SPNs are excited twice: firstly via the known direct pathways (IT-SPN and PT-SPN) and secondly via this previously unknown indirect circuit (PT-ChI-SPN) that enhances the initial excitation. What was the purpose of this double arousal? The authors speculated that the direct IT-SPN connection initially primed specific motor actions, while the PT-ChI-SPN connection subsequently elicited movement.

“Besides movement execution,” noted Nicolas Morgenstern, “this second phase of arousal, mediated by PT neurons, may be important to induce long-lasting changes in the strength of specific connections via the neurotransmitter ACh. This could be important for behavior since learning occurs when connections between brain cells change.” As a result, this study can not only give us insights into the wiring of brain circuits that control movement and behavior, and help us understand the different roles of IT and PT cells, but also provide us with an important piece in the puzzle of how we learn.

“There’s still a lot to explore,” says the study’s lead author, Rui Costa, professor and director at Columbia University’s Zuckerman Mind Brain Behavior Institute. “For example, we’re interested in whether this circuitry is affected in diseases like Parkinson’s or Huntington’s disease.” While there’s still a lot to unravel, this study helped to learn a little bit more about learning.