Home Medizin Neurowissenschaftler entdecken überraschende Rolle von Glia bei der Regulierung neuronaler Reaktionen im Gehirn

Neurowissenschaftler entdecken überraschende Rolle von Glia bei der Regulierung neuronaler Reaktionen im Gehirn

von NFI Redaktion


Researchers at the Fred Hutchinson Cancer Center have discovered that a commonly overlooked type of brain cells called Glia play a larger role in brain function than previously thought.

In the journal Cell Reports, Fred Hutch neuroscientist Aakanksha Singhvi, PhD, and her team report that a single Glia cell uses different molecules to communicate with different neurons. Careful clustering of these molecules ensures that the Glia cell can have a unique „conversation“ with each neuron. Through these molecular mediators, Glia cells can influence how neurons respond to environmental cues like temperature and smell.

Cell Reports published the study online on February 27.

„This is the first very clear indication that a Glia cell will send specific molecules to specific contact sites to regulate these neurons at the single-cell level, which has consequences for the behavior of the animal.“

– Aakanksha Singhvi, PhD, Assistant Professor, Basic Sciences Division at Fred Hutch

While Neurons often receive the most attention due to their central role in our thoughts, sensations, and behaviors, Glia cells – which make up about half of the cells in the brain – were overlooked. Glia cells were previously considered mere „glue“ helping neurons stick together, or „nursemaids“ providing nourishment but no guidance to neurons.

Singhvi is one of the neuroscientists advocating for a reassessment of the importance of Glia.

„In recent years, the realization that Glia cells can contribute to many brain disorders, from epilepsy to Alzheimer’s, is growing,“ said Singhvi. „To get a more holistic and clinically relevant picture of brain function, we need to go back to the basics and better understand how Glia cells and neurons work together.“

To explore the basic biology of Glia cells, Singhvi helped develop the use of Caenorhabditis elegans, tiny transparent worms with exactly the same number of cells, including 302 neurons and only 56 Glia cells per animal. Even though we seem to have little in common with worms, their neurons and Glia cells function similarly to ours.

Singhvi and Sneha Ray – the lead author of the Cell Reports study and a graduate student in Singhvi’s lab – focused on one of these Glia cells called Amphid Sheath (AMsh) to see how it interacted with a sensory neuron called AFD that measures temperature in C. elegans.

Using powerful microscopes to examine individual neurons and Glia cells, the researchers looked for a protein called KCC-3, which Singhvi had previously discovered to help in signal transmission across cell membranes. The researchers quickly discovered that KCC-3 was not evenly distributed along the membrane of the Glia cell. Instead, the protein gathered at a location along the interface between the Glia cell (AMsh) and the sensory neuron (AFD).

„We found it sitting next to the temperature-sensitive neuron – but not to any of the others – essentially, it’s the half-micrometer-sized Glia cell that is different between the two neurons,“ Singhvi said.

The team discovered at least three types of molecular clusters connecting the AMsh Glia with different sensory neurons.

Ray and Singhvi also found that although each neuron encapsulated by AMsh perceives a different environmental stimulus, the Glia cell can help integrate information across circuits and enable neurons within one sensory circuit (e.g., temperature) to influence the function of neurons within another circuit (like those detecting specific odors). This way, a single Glia cell can help the worm respond to the larger environmental picture, rather than just helping neurons relay individual external signals.

„When you think about what it takes to be a roundworm, it’s very complex,“ said Singhvi.

What does a worm do when it encounters an enticing smell signaling food? Exactly at that moment when its environment becomes dangerously warm? It has to weigh these different inputs and make a decision.

„The worm doesn’t burn – it’s too smart to burn,“ said Singhvi.

The compartmentalization they and Ray uncovered is likely crucial for the life of a roundworm – or human – in its ability to weigh important factors like heat and smell, she said. This allows the animal to have multiple circuits function properly at the same time without any crosstalk.

Regarding potential implications for human brain health, Singhvi pointed out that the same KCC-3 protein she studied in nematodes is essential for brain function in humans. Disruptions of KCC-3 are related to a severe brain development disorder known as Agenesis of the Corpus Callosum or Anderman Syndrome, as well as seizure susceptibility and neurodegeneration. Differences in brain circuits are associated with disorders such as autism, epilepsy, and schizophrenia.

„Our brain routinely processes multiple inputs or sensory cues in parallel,“ said Singhvi. „Our research shows that Glia can serve as mediators between brain circuits, helping us understand the various ways in which circuits can be disrupted.“

Source:

Fred Hutchinson Cancer Research Center

Journal Reference:

Ray, S., et al. (2024) Neuronal Cilia Tethers Glial KCC-3 to a Microdomain to Regulate Multisensory Processing. Cell Reports. doi.org/10.1016/j.celrep.2024.113844.

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