This post was originally published on here
Understanding how the brain processes information remains one of science’s toughest challenges. Every thought, memory, and decision relies on neurons exchanging chemical messages at incredible speed.
For decades, most tools focused on signals neurons send out, such as electrical and calcium activity. The chemical messages arriving at neurons, however, remained largely invisible.
A newly engineered protein now changes that situation by revealing incoming chemical messages with high precision. Access to these signals offers a clearer view of how learning, memory, and brain disorders take shape.
Chemical signals guide the brain
Brain cells, also called neurons, communicate using chemicals known as neurotransmitters. Glutamate is the most common excitatory neurotransmitter in vertebrate brains.
A single electrical impulse often releases only one packet of glutamate molecules. Each packet exists inside a synapse for less than a millisecond before disappearing. This combination of speed and small size makes detection extremely difficult.
Earlier tools measured calcium or electrical changes linked to outgoing activity. Incoming glutamate signals remained too faint to track across many synapses at once. This lack of access limited understanding of how neurons combine information.
Brain inputs shape thinking
Each neuron receives input from thousands of synapses. Every synapse contributes a small chemical signal. Brain computation depends on how dendrites and cell bodies combine these signals over short time windows.
Scientists debate whether important calculations happen mainly in dendrites or near the cell body. Direct observation of glutamate release allows researchers to test such ideas. Patterns of glutamate arrival reveal which inputs drive neuron firing and which inputs remain ignored.
Access to synaptic input also helps explain how memory forms through synaptic plasticity, in which repeated activity strengthens or weakens connections.
New sensors expose brain signals
Researchers at the Allen Institute for Neural Dynamics and HHMI’s Janelia Research Campus engineered a new family of glutamate sensors called iGluSnFR4.
Protein engineering focused on improving brightness, sensitivity, and timing. Hundreds of protein variants underwent testing in cultured neurons and living brains.
Two versions emerged as top performers. iGluSnFR4f shows fast signal decay, allowing tracking of rapid synaptic events. iGluSnFR4s shows slower decay but stronger signals, allowing monitoring of large synapse populations.
Both of these protein variants detect glutamate release from single vesicles inside living brain tissue.
Watching brain signals live
New sensors allow imaging across brain regions such as the cortex, hippocampus, thalamus, and midbrain.
Signals appear with high spatial precision, meaning neighboring synapses remain distinct rather than blurred together. Fast activation times allow accurate measurement of release timing.
In sensory brain regions, glutamate patterns follow external stimuli with millisecond precision.
Rapid versions capture closely spaced inputs, while slower versions capture weaker signals over wider areas. This flexibility allows scientists to match sensor choice to research goals.
Brain disorders disrupt signaling
Abnormal glutamate signaling links to Alzheimer’s disease, epilepsy, schizophrenia, autism, and other neurological conditions.
Many disorders involve disrupted synaptic communication rather than complete neuron loss. Measuring incoming glutamate helps locate where communication fails.
Drug researchers benefit as well. New sensors allow direct observation of how experimental treatments change synaptic activity.
Instead of guessing effects from behavior or electrical signals alone, researchers can now see chemical communication directly.
Mapping brain communication
“It’s like reading a book with all the words scrambled and not understanding the order of the words or how they’re arranged,” said Dr. Kaspar Podgorski, a senior scientist at the Allen Institute for Neural Dynamics and lead author.
“What we’re doing here is adding the connections between those neurons and by doing that, we now understand the order of the words on the pages, and what they mean.”
Neuroscientists can map the structural connections between neurons and, in separate experiments, measure neural activity, but combining these two views has been difficult.
As a result, researchers have struggled to determine which neurons are communicating with specific partners.
“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,” said Dr. Podgorski.
New directions in brain research
New glutamate sensors remove a long-standing barrier in neuroscience. Researchers can now observe how information flows through neural networks rather than guessing from partial signals.
With public availability through Addgene, laboratories worldwide can adopt these tools. Wider use may lead to deeper understanding of learning, memory formation, and neurological disease.
“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 study co-author Dr. Jeremy Hasseman.
The research is published in the journal Nature Methods.
—–
Like what you read? Subscribe to our newsletter for engaging articles, exclusive content, and the latest updates.
Check us out on EarthSnap, a free app brought to you by Eric Ralls and Earth.com.
—–
