Researchers have engineered a protein that detects subtle glutamate signals between neurons, unveiling a previously hidden aspect of brain communication. This tool allows real-time observation of how brain cells process incoming information, potentially advancing studies on learning, memory, and neurological disorders. The findings, published in Nature Methods, highlight a breakthrough in neuroscience.
The brain's neurons communicate through electrical and chemical signals, but until now, scientists could only observe the outgoing electrical messages, leaving incoming chemical exchanges largely invisible. A new protein sensor, iGluSnFR4—pronounced 'glue sniffer'—changes that by capturing faint glutamate releases at synapses in real time. Glutamate, the brain's primary excitatory neurotransmitter, is crucial for processes like learning and memory, yet its brief, weak signals have been hard to measure.
Engineered by teams at the Allen Institute and HHMI's Janelia Research Campus, iGluSnFR4 acts as a molecular indicator sensitive enough to detect even the smallest synaptic events. This enables researchers to see how individual neurons integrate thousands of inputs before deciding to fire, shedding light on complex brain computations underlying thoughts and decisions.
"It's like reading a book with all the words scrambled and not understanding the order of the words or how they're arranged," explained Kaspar Podgorski, a lead author and senior scientist at the Allen Institute. "What we have invented here is a way of measuring information that comes into neurons from different sources, and that's been a critical part missing from neuroscience research."
The tool also holds promise for disease research. Disruptions in glutamate signaling are implicated in conditions including Alzheimer's disease, schizophrenia, autism, and epilepsy. By precisely monitoring these signals, scientists can better understand disease mechanisms and test potential therapies.
Collaboration was key to the sensor's success. "The success of iGluSnFR4 stems from our close collaboration started at HHMI's Janelia Research Campus between the GENIE Project team and Kaspar's lab," said Jeremy Hasseman, a scientist at Janelia. The protein is now available to researchers via Addgene, fostering wider use in neuroscience.
This advance bridges a gap in observing full neural conversations, moving beyond fragmented views to comprehensive insights into brain function.
