“Zombie neurons” reveal how the brain learns, study finds
Although functionally alive, Zombie Neurons interact differently within the brain circuit, hindering the animals' ability to learn conventionally. (CREDIT: Creative Commons)
The cerebellum, a brain region crucial for learning and coordinating movements, has recently gained attention due to a study conducted by researchers at the Champalimaud Foundation.
This study sheds light on the mechanisms underlying learning processes within the cerebellum, particularly through the discovery of what they term "zombie neurons."
The cerebellum and how the brain learns
The cerebellum, often referred to as the "little brain," contains more than half of the brain's neurons. It is responsible for tasks such as coordinating movements and maintaining balance, essential for activities like walking or playing sports. Additionally, it facilitates the learning process by associating sensory cues with specific actions, allowing individuals to adjust their movements based on past experiences.
Example coronal section of cerebellar cortex indicating fiber placement in the eyelid area of the cerebellar cortex (white arrow) and labeling Purkinje cell ChR2 expression (green) and calbindin (magenta). Similar expression and fiber placement were observed in 11 mice. (CREDIT: Nature Neuroscience)
To understand how learning occurs in the cerebellum, researchers focused on the role of climbing fibers, a type of cerebellar input, and their interaction with Purkinje cells, another type of neuron in the cerebellum. They conducted experiments using mice and a learning task called eyeblink conditioning, where mice learn to blink in response to a specific sensory signal, such as a light, which precedes a gentle puff of air aimed at their eye.
Dr. Tatiana Silva, the lead author of the study, explains that they used a technique called optogenetics to manipulate the activity of climbing fibers with precision.
By activating these fibers with light, they were able to induce associative learning in mice, causing them to blink in response to a visual cue even in the absence of the usual sensory stimulus.
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Further experiments revealed that climbing fibers are not only sufficient but also necessary for associative learning in the cerebellum.
When the researchers silenced climbing fibers during the presentation of the sensory signal, mice failed to learn the task, highlighting the critical role of these neurons in the learning process.
However, an unexpected finding emerged during the experiments. The researchers discovered that by introducing a light-sensitive protein called Channelrhodopsin-2 (ChR2) into climbing fibers, they unintentionally altered the neurons' natural properties. This alteration prevented climbing fibers from responding appropriately to standard sensory stimuli, impairing the animals' ability to learn using traditional methods.
Example coronal sections (representative of six mice) of cerebellar cortex showing expression of ChR2 in granule cells (Gabra6-ChR2, magenta; Pkj-calbindin, green) and fiber placement in the eyeblink area of the cerebellar cortex (white arrow). (CREDIT: Nature Neuroscience)
Despite this impairment, the mice showed successful learning when climbing fibers were stimulated with light instead of the usual sensory signal. This unintentional manipulation of neuron activity, termed "zombification" by Dr. Silva, led to the designation of these altered neurons as "zombie neurons."
Although functionally alive, they interacted differently within the brain circuit, hindering the animals' ability to learn using conventional methods.
Example sagittal section of cerebellar cortex. Similar expression was seen in eight mice. Jaws (green) is expressed in CF inputs to Purkinje cells (magenta). (CREDIT: Nature Neuroscience)
Dr. Megan Carey emphasizes the significance of these findings, stating that they provide compelling evidence for the essential role of climbing fiber signals in cerebellar learning. Future research will focus on understanding why the expression of ChR2 leads to these unexpected effects and whether similar findings extend to other forms of cerebellar learning.
These findings not only enhance our understanding of the cerebellum's role in learning but also raise intriguing questions about the manipulation of neuron activity and its implications for cognitive processes.
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