High-resolution extracellular electrophysiology is typically used to record from neurons in order to understand brain function. Combining electrophysiology with optogenetics allows researchers to test the causal role of specific neurons by activating or inactivating those populations while recording the effects of neural activity.
Now, a new technology, co-developed by UCL scientists, simultaneously records and manipulates neuronal activity deep within the brain. The device, known as Neuropixels Opto and researched in mice, integrates electrophysiology and optogenetics in a single probe, enabling unprecedented insight into how individual neurons in the brain function and interact. By packing around 1,000 closely spaced recording sites onto an ultra-thin probe, it is possible to capture high-resolution signals from individual brain cells while monitoring large neural networks at the same time. The device could transform our understanding of neural circuits and neurological conditions, such as Alzheimer’s disease and schizophrenia.
“This makes it possible, for the first time, to directly test how specific neurons influence the activity of surrounding circuits—revealing causal relationships between neuronal activity and brain function,” notes Matteo Carandini, PhD, a professor at the UCL Institute of Ophthalmology. “The ability to both record and control neuronal activity in the same experiment represents a significant advance for neuroscience.”
This work is published in Nature Methods in the paper, “Neuropixels Opto: combining high-resolution electrophysiology and optogenetics.” The device, which packs 960 electrical recording sites and two sets of 14 light emitters onto a 70-μm-wide, 1-cm-long shank, allows spatially addressable optogenetic stimulation with blue and red light. The device allows researchers to monitor the electrical activity of hundreds of neurons while also selectively activating or silencing specific cells using light.
“The brain processes information through complex patterns of electrical activity, with billions of neurons communicating via rapid electrical signals,” explains Carandini. “Understanding how these signals give rise to behavior, thought and disease requires tools that can both observe and influence neuronal activity.”
“Until now, scientists have typically relied on separate approaches: electrophysiological probes to record neural activity, and optogenetics to control it,” Carandini adds. “Combining the two has proved challenging, particularly in deeper brain regions, where delivering light without disrupting sensitive recordings is technically difficult. Neuropixels Opto overcomes these limitations by integrating both capabilities into a single device, enabling simultaneous measurement and manipulation of neural circuits.”
Karolina Socha, PhD, research fellow at UCL Institute of Ophthalmology, has used the probes to investigate the function of the cerebral cortex. “We were surprised to discover that the activity of neurons in the cortex can be remarkably localized. Up to now, we thought that neurons are so interconnected that there would be no way to activate some of them without activating many others,” she said. “The new Neuropixels Opto probes revealed that these neurons can operate not only in concert but also rather independently.”
The technology may also have important implications for understanding neurological and psychiatric conditions. Many disorders, including schizophrenia, Alzheimer’s Disease and Parkinson’s Disease, are associated with disruptions in how neurons communicate. By providing a clearer picture of how neural circuits function in both healthy and diseased states, Neuropixels Opto could support the development of more targeted treatments.
