Berkeley Researchers Map Brain Connectivity With New Optogenetic Platform
“It’s the first time we’ve been able to activate specific ensembles in one cortical area and map the functional impacts across three, five or even six other cortical areas,” says Hillel Adesnik, professor of neuroscience at the University of California, Berkeley.
Holographic Stimulation Triggers Visual Information Flow
The research team used the platform to stimulate neurons in four distinct areas of the mouse visual cortex while recording activity from thousands of neurons in six other surrounding areas. To test if the system could transmit meaningful data, the team trained a machine-learning classifier to recognize activity patterns created when mice viewed four different orientations of black and white parallel lines.
After identifying the specific neurons in visual area V1 tuned to those orientations, the researchers stimulated those cell groups. The classifier successfully categorized the downstream activity as the correct orientation significantly above chance, which indicates the platform can write activation patterns that transmit visually relevant information between brain regions.
Mirrors Expand the Field of View
Mapping functional connectivity requires the ability to stimulate neurons in different regions rapidly while simultaneously recording from surrounding areas. The team solved this by adding an arrangement of mirrors that quickly repositions stimulation anywhere within the mesoscope’s field of view (FOV).
Lamiae Abdeladim, a postdoctoral researcher in Adesnik’s lab, states this tactic increased the accessible stimulation area by an order of magnitude. This setup allowed the team to stimulate two different visual cortex areas while recording across the entire FOV to derive connectivity maps. While local activity remained primarily inhibitory—consistent with previous studies—the team discovered that the effect on activity in different regions was more excitatory, a new finding in the field.
New Tools Enable Causal Experiments and Brain-Machine Interfaces
Abdeladim notes that perturbing functionally defined ensembles of neurons across multiple cortical areas was not possible with any other optical or non-optical technique, opening a new class of causal experiments for neuroscience. Sean Quirin, an assistant professor of psychiatry and behavioral sciences at Stanford University who was not involved in the study, says these tools are necessary to begin teasing out the “language of the brain.”
Quirin suggests the findings could eventually inform the development of brain-machine interfaces by identifying what is essential for neural communication. He notes that neuromodulation is becoming increasingly clinically relevant for helping patients live better lives.
Scaling Optogenetics to Larger Brains
The researchers intend for the use of a commercially available mesoscope to encourage other research groups to adopt the platform. Future improvements may include increasing the pixel density of the spatial light modulator (SLM) to expand the FOV of optogenetic holographic stimulation.
Adesnik says that larger FOVs may eventually allow the scaling of two-photon optogenetics to animals with larger brains, including nonhuman primates.
Neural Mapping Questions
Can this platform be used on humans?
The current research was conducted on mice, but Adesnik indicates that increasing the field of view could eventually scale the technology to larger brains, such as nonhuman primates.
What is a mesoscope in this context?
A mesoscope is an imaging tool that allows researchers to record activity from thousands of neurons across a wide field of view while simultaneously stimulating specific ensembles of cells.
How does the machine-learning classifier help the study?
The classifier was used to verify that the stimulated patterns in the brain actually represented visual information (such as line orientation) and that this information was successfully transmitted to other brain regions.
“I’m excited about figuring out how do we design these excitation patterns to maximally communicate this information?”
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