Lighting up the circuits of the cerebellum

New McGill study sheds light on the cerebellar nuclei 

In a new article published today in Nature Communications, a team of McGill researchers led by Professor Alanna Watt of the Department of Biology examines the spatial organization of neurons in the cerebellar cortex. The findings offer new insight into how information is integrated in the cerebellum and shed light on the role of the often-overlooked cerebellar nuclei. 

Connections between neurons in the brain form circuits that shape brain function. Identifying how neurons are “wired up” to each other is key to understanding how regions of the brain, such as the cerebellum, carry out specific functions. 

Kim Gruver, a former McGill PhD researcher and first author of the study, offered the analogy of an electrical circuit to explain how neuroscientists build their understanding of neurons. 

“We might determine that a battery provides current through a wire to activate a motor by observing the wire’s position relative to both the battery and the motor,” said Gruver, who’s now working at the Allen Institute for Brain Science. “Similarly in neuronal circuits, what a neuron is connected to is usually a big clue as to what the neuron does.” 

This new study takes a closer look at the synapses -- the structures that allow neurons to communicate with one another – formed between Purkinje cells and neurons in the cerebellar nuclei. Despite the important role that they play in cerebellar information processing, cerebellar nuclei aren’t as well-understood as other parts of the brain. 

“Some brain regions get more attention than others. This means that while we have a good understanding of what some brain areas do, others are much more mysterious,” said Watt. “The cerebellar nuclei have historically fallen more into the ‘mysterious’ category, and we have not really understood how inputs converge on neurons there. Until we understand that, we are really in the dark about how this brain region functions.” 

The researchers used electrophysiology and focal optogenetic stimulation in mice to build spatial connectivity maps of Purkinje cell inputs onto cerebellar nuclei neurons. Purkinje cells are found throughout the cerebellum, but are organized into different zones that are thought to have different functions. While many of the neurons in the nuclei received inputs from cells lying within just one zone, a significant number of neurons received inputs from cells from all four zones. 

“Our observations indicate that neurons in the cerebellar nuclei receive inputs from Purkinje cells that likely encode very different types of information,” said Watt. “For example, one cell might receive inputs encoding motor information, emotional salience, and whether something is rewarding. This suggests that neurons in the cerebellar nuclei are integrating and encoding rich and complex information from cerebellar Purkinje cells.” 

These findings suggest that the cerebellar nuclei are more dynamic than previously understood and may be an important hub of multimodal information integration in the cerebellum. 

“Understanding a brain circuit gives us insight into what that circuit does, and thus this information is important, both for healthy brain function and when function is altered in disease,” said Watt. 

Read the full paper here. 

Citation

Gruver, K.M., Jiao, J.W.Y., Fields, E. et al. Structured connectivity in the output of the cerebellar cortex. Nat Commun 15, 5563 (2024). https://doi.org/10.1038/s41467-024-49339-1