Studying brain cell activity has never been easy. The central nervous system is incredibly complex, and untangling the dense network of bioelectrical signals within it is like trying to piece together an 85 billion piece puzzle. One of the biggest challenges in this endeavor was that previously researchers could only measure the signals that individual brain cells produce, not the signals they receive.
Now a protein with a very unusual name has allowed neuroscientists to study the signals entering brain cells.
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Creation of the iGluSnFR4 protein
The carefully modified protein, developed by a team at the Allen Institute and the Howard Hughes Medical Institute's Janelia Research Campus, records the complex chemical signals that electrically active neurons use to communicate. The most common of these chemicals is called glutamate. It is important for brain processes such as thinking and memory.
Because it detects the level of glutamate released by neurons, it was named iGluSnFR4 (“glue analyzer”). new Natural Methods The paper demonstrates the latest generation of glue protein analyzer, which overcomes significant barriers faced by previous versions.
Tracking Signals in the Brain
To understand why a tool such as a glue analyzer is so in demand in neuroscience, it is important to understand how brain the alarm is working. The output of a single neuron is (relatively) easy to understand. These cells emit electrical signals that travel along cable-like axons until they reach the neuron's transmission area called a synapse, where they are converted into chemical messengers called neurotransmitters, such as glutamate, that can “jump” the gap between cells.
What triggers this electrical and then chemical signal is much more complex: neurons receive neurotransmitter inputs from potentially thousands of others brain cells. Neurons interpret these signals and determine whether they should respond with an electrical signal of their own. However, these chemical effects have always been too weak and too rapid to be measured reliably.
Before the advent of glue-sensing proteins, neuroscientists were essentially unable to hear half the electrical conversation that occurs between cells in our bodies. brain.
“Neuroscientists have pretty good ways of measuring the structural connections between neurons, and in individual experiments we can measure what some neurons in the brain are saying, but we haven't been able to combine these two types of information. It's hard to measure what neurons are saying to which other neurons,” said Kaspar Podgorski, co-author of the study and a neuroscientist at the Allen Institute, in a statement. press release.
Glue interceptor proteins are changing that.
“It’s like reading a book with all the words mixed up and not understanding the order of the words or how they are arranged,” Podgorski said. “I think what we're doing here is adding connections between these neurons, and through that we now understand the order of the words on the pages and what they mean.”
Listening to the hidden conversations of the brain
In the new paper, the team demonstrates a pair of proteins, iGluSnFR4f and iGluSnFR4s, that measure fast signals and signals produced by large groups of brain cells, respectively.
In a series of experiments, the team demonstrated that the proteins can measure brain activity in mice, indicating activity with a fluorescent signal that can be imaged using a microscope.
The authors hope these tools will help neuroscientists understand the computations that allow the brain to function. These tools can also help us understand what happens to our brains when glutamate signaling is disrupted in conditions such as schizophrenia and epilepsy.
“What we've invented here is a way to measure information coming into neurons from different sources, and that's the critical piece missing from neuroscience research,” Podgorski concluded.
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