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Researchers have developed a two-photon imaging platform called FlatMux that captures electrical activity from nearly 200 neurons simultaneously across cortical layers at a rate of 150 million samples per second. Published in Nature Methods, the technology records high-speed neural voltage signals at depths up to 500 micrometers, allowing scientists to track how information moves through densely interconnected living brain circuits in real time.
The Slow Limits of Calcium Imaging
For years, neuroscientists studying complex neural networks relied heavily on calcium imaging to monitor brain activity. According to Alipasha Vaziri, head of the Laboratory of Neurotechnology and Biophysics at Rockefeller, calcium signals offer only an indirect measure of electrical firing. They operate much slower than the millisecond impulses neurons use to communicate, meaning traditional calcium sensors miss rapid sub-threshold responses that occur before a neuron fires.
To capture direct electrical changes, researchers previously turned to genetically encoded voltage indicators (GEVIs). Yet GEVI signals are faint, roughly 100 times faster than calcium dynamics, and extremely difficult to record deep inside scattering brain tissue. While two-photon microscopy helps peers inside tissue, standard setups suffer from severe light-delivery inefficiencies. Excessive laser power can heat tissue and degrade sensors, while insufficient power yields unusable data.
Engineering Optical Efficiency with FlatMux
To solve these hardware constraints, Vaziri and his research team built FlatMux to optimize optical excitation efficiency. By maximizing the output of fluorescent photons relative to the input laser power, the platform successfully records from nearly 200 neurons within one or multiple planes concurrently. According to findings detailed in News-Medical, the system scans laser pulses at 2,000 frames per second at depths reaching 500 micrometers.
This speed and depth capability lets researchers map functionally connected neurons and observe causal interactions directly. Unlike electrode arrays, direct optical voltage imaging preserves spatial context. This enables scientists to simultaneously infer the precise anatomical location and cell type of each recorded neuron.
Listening to Distributed Neural Networks
“For a long time the field has been focused to understand the brain in terms of response properties of individual neuron,” Vaziri stated, as reported by News-Medical. “Our imaging platform makes it possible to instead investigate how various brain functions could be the result of information processing by a highly interconnected system where computation is distributed across large network of neurons.”
Mapping the Physical Basis of Cognition
The introduction of FlatMux marks a shift from studying isolated cells to observing distributed computations across large neural populations. By capturing fast voltage transients deep inside cortical tissue, the platform provides a clearer picture of how sensory inputs transform into behavioral outputs. Future applications of the technology will focus on mapping large-scale circuit dynamics to better understand the physiological basis of cognitive functions in healthy and diseased states.
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