A recent study led by a team at the Champalimaud Foundation has shed new light on the precise mechanisms underlying the cerebellum's learning processes, with a serendipitous discovery of "zombie neurons." Findings from the study were published in Nature Neuroscience.
The cerebellum, which holds more than half of the brain's neurons, is essential for linking sensory cues with specific actions, allowing us to perform everyday tasks smoothly. For learning to occur, the cerebellum continuously monitors the outside world and the outcomes of our movements, using "error" or "teaching signals" to adjust the strength of brain connections and modify our behavioral responses.
The team used optogenetics, a technique that allows for precise control of brain cells using light, to investigate the role of climbing fibers, a specific class of cerebellar inputs, in associative learning. They found that activating climbing fibers could trick mice into learning to blink in response to a visual cue, even in the absence of the expected sensory stimulus. Conversely, silencing climbing fibers during the presentation of the sensory stimulus prevented the mice from learning the association.
Unexpectedly, the researchers discovered that introducing a light-sensitive protein into the climbing fibers altered their natural properties, preventing them from responding appropriately to standard sensory stimuli. These "zombie neurons," as the researchers dubbed them, were functionally alive but not interacting with the brain circuit as usual. Remarkably, the mice were still able to learn when the researchers paired climbing fiber stimulation, rather than the sensory stimulus, with the visual cue.
The findings from this study provide the most compelling evidence to date that climbing fiber signals are essential for cerebellar associative learning. The researchers are now focused on understanding the mechanisms behind the "zombification" of the neurons and determining whether their findings extend to other forms of cerebellar learning.