Researchers create zombie neurons in mice to reveal learning secrets

Researchers create zombie neurons in mice to reveal learning secrets

The brain is much more than a mass of interconnected neurons, but even though it is much more than that, it is still a part of it. There are glial cells, there are connections with the endocrine system, and, in general, there are stimuli coming from all parts of the body, issues that add complexity, but do not greatly simplify the otherwise inaccessible task of unraveling the myriad neural connections. Which you cross. So, studies like the one just published Normal neuroscience About the newly discovered “zombie neurons” are a breath of fresh air, especially for the study of human learning.

In this study, a group of researchers from the Champalimaud Foundation studied the way rats learn that two stimuli are related. Specifically, they applied variations of the classic experiment of associating a visual stimulus with a hit to the eye, such that people end up closing their eyes before receiving the hit, caused by the sound they have learned to “fear.” Up to this point, this methodology is considered fairly classical, but then a breakthrough appears: gene editing and stimulating neurons with light.

In fact, to be precise, the research is not studying the brain, but rather the cerebellum, which is another part of the brain. Because the brain is not the entire nervous system that surrounds our skull, that is, the brain that is divided into three parts, the brain itself with its two halves and its many thick wrinkles, and the brainstem that connects the brain to the spinal cord. Between one and the other is the cerebellum, which is two small lobes at the back of our neck, very wrinkled, and containing, oddly enough, nearly half of the neurons in our brain.

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This simple structure appears to be responsible for many motor functions that we consider basic. In fact, to sum it up a lot, we can say that it is responsible for our ability to maintain balance, as well as perform smooth and coordinated movements. In fact, it has a huge role in sports, where it also helps us associate stimuli with specific responses, such as a stop from a goalkeeper or a boxer's dodge. And that's exactly what they studied: how changes in the cerebellum relate to learning these associations.

To study it, the researchers repeated the classic light-and-blow experiment with mice, but instead of subjecting them to a classic stimulus, they selectively activated climbing neurons, cells through which information about stimuli normally reaches the cerebellum and which appeared to be involved in learning. . To do this, they genetically modified mice, causing them to secrete molecules on the surface of climbing cells that made them sensitive to light, so they could stimulate them with short bursts of electromagnetic radiation.

After repeatedly stimulating the climbing cells before blowing into the mice's eyes, the animals learned to blink only when the climbing cells were stimulated. Furthermore, when optogenetic techniques were used to silence the climbing cells, the mice were unable to learn anything. These two results confirm that climbing cells have an important and necessary role in cerebellar motor learning. This is indeed progress, but I was hoping for one final development: zombie neurons.

Interestingly, mice genetically modified for these optogenetic techniques could learn to associate climbing fiber activity with puffing, but they could not associate classical visual stimulation with puffing. In other words: the classic experiment on which this was based didn't work with mice. The climbing fibers were able to function if we stimulated them directly, but they did not seem to respond to conventional stimuli. They were as if they were dead in life, which is why they were called zombies.

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Its surface is filled with a protein known as Channelrhodopsin-2 (ChR2), but its relationship to this specificity is unclear. In the words of Dr. Megan Curry: “These results represent the most convincing evidence to date that climbing fiber signals are essential for cerebellar associative learning.. “Our next steps include understanding why ChR2 expression leads to ‘zombie’ neurons and determining whether our findings extend to other forms of cerebellar learning.”

We will have to continue researching, but the discovery of these strange neurons opens the doors to completely original research They can shed light on the workings of our brains and, more specifically, on learning.

Don't be known:

  • Although we usually talk about the brain to refer to the brain as a whole, this is not the most appropriate way to call it. The brain is a group of central nervous system structures located in our skull, and the cerebrum is only one of its parts.

References (MLA):

  • “Neural learning signals for associative cerebellar learning.” Normal neuroscience 10.1038/s41593-024-01594-7

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