A scientific paper by Dr. Balázs Rózsa (BrainVisionCenter, Institute of Experimental Medicine), Dr. Attila Losonczy (UT Southwestern Medical Center), and their co-authors was published in the March issue of Neuron, one of the world’s leading journals in neuroscience. The study, titled “Movement-stabilized three-dimensional optical recordings of membrane potential changes and calcium dynamics in hippocampal CA1 dendrites,” presents a three-dimensional real-time motion-correction method developed through the collaboration of BrainVisionCenter (BVC)—founded by Botond Roska and Balázs Rózsa—and Femtonics Ltd.
This technology has, for the first time, made it possible to measure the brain’s elementary functional units—neurons and their processes, the so-called dendrites—in a continuously pulsating, moving brain, at the extremely fast timescales characteristic of brain activity, reaching speeds of several kilohertz. Under the leadership of Attila Losonczy and Balázs Rózsa, the researchers implemented rapid image stabilization together with simultaneous high-resolution, AI-assisted measurements in three dimensions.
The instrument—protected by more than 50 international patents—is manufactured and distributed by Femtonics Ltd. Its users include leading universities and research institutes such as Stanford University, Yale University, Columbia University, Harvard University, Boston University, the University of Oxford, McGill University, the University of Helsinki, MIT, and Caltech.
The publication in Neuron marks the 25th high-impact paper published in a Nature Index journal generated by the Institute of Experimental Medicine and BrainVisionCenter using a Femtonics instrument. This is considered a record achievement in the Hungarian high-tech sector. Globally, several hundred high-ranking scientific publications have been published using Femtonics laser microscopes. Revenue generated from the sale of this instrument platform has exceeded HUF 10 billion, which the company has reinvested in full into medical research and innovation.
The technology presented in the Neuron paper could enable intraoperative measurement of activity in the pulsating human brain, opening new avenues in medical diagnostics and therapy. It is capable of tracking motion of up to 1 mm while measuring the moving brain with 100-nanometer precision—approximately one-thousandth of the thickness of a human hair. Researchers at BVC and Femtonics are now working on the development of suitable sensors for human brain measurements, paving the way toward clinical application.
The key scientific breakthrough enabled by this invention is that dendritic integration and back-propagating action potentials—previously studied mainly in vitro—can now also be observed in awake, behaving animals, and tracked along the complex, tree-like branching processes of neurons, while filtering out motion-related artifacts arising from brain tissue movement, respiration, and heartbeat. The system can reposition the measurement coordinate system in less than 100 microseconds (i.e. 0.0001 seconds), thereby compensating for tissue displacement. In essence, it functions as a high-speed 3D image stabilizer used during laser scanning, resulting in stable images and signals free from motion noise.
One of the method’s major innovations is that, instead of using previously introduced artificial fluorescent beads in the brain, the neuronal soma itself can serve as the reference point for motion tracking. Because this approach does not trigger an immune response, it avoids damage to the brain and enables more accurate measurements. In addition, the method reduces motion-induced measurement artifacts by more than two orders of magnitude.
Imaging based on the widely used calcium sensors provides only indirect information about electrical activity, and therefore offers a more temporally blurred view of brain function. By contrast, in the present study conducted by UT Southwestern Medical Center, BrainVisionCenter, and the Institute of Experimental Medicine, newly developed genetically encoded voltage sensors, used alongside calcium sensors, directly report electrical changes in the brain with a temporal precision of up to one ten-thousandth of a second. Until now, such measurements had not been feasible in vivo, at subcellular resolution and in 3D, because no sufficiently fast measurement technology existed.
The required technological breakthrough was provided by Femtonics’ acousto-optic technology, which enabled 3D measurements that are 6–7 orders of magnitude faster. This dual functional labeling approach allowed researchers to visualize electrical signals and the calcium responses they evoke at the same time. For labeling, Attila Losonczy’s group developed a novel rapid genetic delivery method based on in vivo electroporation, which yielded stronger contrast and better functional signals than any previous method, while leaving the brain unharmed.
The results show that responses measured in individual dendritic spines become progressively weaker as signals back-propagate along neuronal processes, the so-called dendrites. In contrast, trains of action potentials generate more sustained depolarization, allowing information to reach distal dendrites more reliably. Signals evoked by targeted photostimulation showed the same distance-dependent attenuation, suggesting that dendritic filtering arises primarily from the neurons’ own intrinsic properties. In addition, the researchers detected local dendritic voltage events that were independent of activity in the neuronal soma. This indicates that individual dendritic branches may function as partially autonomous computational subunits, almost like independent processors.
Another important finding is that—contrary to the currently prevailing view—the relationship between voltage signals and calcium signals weakens progressively as the number of neuronal branch points increases. In distal dendritic compartments, voltage signals remain measurable, but the corresponding calcium responses decline more rapidly, especially beyond branch points. This suggests that the structure and electrical properties of dendrites influence not only the propagation of voltage, but also calcium influx, thereby enabling branch-specific plasticity and molecular function.
These findings bridge the gap between in vitro dendritic measurements and in vivo neuronal dynamics. They establish a technological foundation for the direct study of dendritic computation during learning and memory formation in awake, behaving animals.
The article is available at:
https://www.cell.com/neuron/abstract/S0896-6273(26)00004-8
