The life-long learning of new motor skills is a rule, not a hobby. If that sounds like a daunting truism, take heart. A recent study reports a newly discovered brain circuit that may be key to learning for a lifetime. Can it be “boosted” for more effective motor learning? It is implicated in movement disorders. Will it teach us how to treat Parkinson’s disease?
The cortex forms the outer layer of the brain; it’s often called the gray matter. The functions of the cortex are many, including voluntary actions, language, memory, and cognition. It’s connected to many other brain regions.
“We were particularly interested in two major types of cells in the cortex, known as IT (intratelencephalic) and PT (pyramidal tract) neurons,” says study first author Nicolas Morgenstern, of the Champalimaud Foundation in Lisbon, Portugal, in a statement. “Both IT and PT cells send signals from the cortex to another area buried deeper in the brain, called the striatum.”
Spiny projection neurons (SPNs) make up 95 percent of the neurons in the striatum. They are directly connected to both IT and PT cells.
To study these corticostriatal connections, the scientists used a technique called optogenetics, a method for controlling the activity of cells using light. “We genetically engineered either IT or PT cells in mice, allowing us to activate these cell types independently, and to measure their different effects on SPNs in the striatum,” explains Morganstern.
It was while using this approach, and recording the activity of neurons in vitro, that the scientists identified the previously unknown corticostriatal pathway. This pathway includes striatal cholinergic interneurons (ChIs). ChIs in the striatum receive input from PT cells and, in turn, excite SPNs. “We found that PT cells preferentially connect to ChIs, which indirectly activated SPNs,” says Morgenstern.
Using pharmacological methods, the scientists showed precisely how ChIs excites SPNs. When activated by PT neurons, ChIs release a neurotransmitter called acetylcholine (ACh). When ChIs releases ACh, they cause the nerve fibers of cells nearby to excite SPNs.
These results demonstrate that SPNs are excited twice. The first excitation is through the known, direct routes. The second excitation is through this previously unknown, indirect circuit, amplifying the initial excitation.
Morgenstern notes, “Besides movement execution, this second excitatory phase mediated by PT neurons could be important for inducing long-lasting changes in the strength of specific connections, via the neurotransmitter ACh. This could be important for behavior since learning happens when connections between brain cells change.”
“There’s still much to explore”, says the study’s senior author, Rui Costa, Professor and Director, Zuckerman Mind Brain Behavior Institute, Columbia University. ”For example, we are interested in understanding whether this circuit is affected in disorders like Parkinson’s or Huntington’s Disease.”
The study is published in Scientific Advances.