Neurobiologists at the University of California San Diego have shown that switching on a mere twenty neurons in the mouse motor cortex can trigger the full pattern of brain activity associated with a learned movement and produce the action itself, according to a study published in Nature.
By combining optical recording with precise light-based stimulation, researchers in the Komiyama Lab demonstrated that a sparse cortical ensemble is sufficient to set a learned movement in motion, answering whether distinctive firing patterns drive behavior or merely echo commands from elsewhere in the brain.
Imaging Neural Activity With Two-Photon Technology
The research team utilized two-photon imaging to monitor the simultaneous activity of hundreds of individual neurons in real time while mice learned and performed new physical tasks.
The method revealed the precise cellular choreography preceding a specific movement rather than relying on coarse population signals.
Using Holographic Optogenetics for Precise Stimulation
The investigators turned to holographic optogenetics, a method that sculpts light into precise three-dimensional patterns, enabling researchers to switch on genetically light-sensitive neurons individually while observing the rest of the network.
The team targeted specific cells identified beforehand through their imaging records, achieving millisecond-scale control over artificial neural activity instead of stimulating a diffuse region of tissue.
This gives us the advantage of being able to observe the activity of neurons during a specific behavior. We can identify the functional properties of neurons and then follow that up by selectively stimulating the neurons of our choice.
Chen
Targeting Early-Onset Neurons in the Mouse Motor Cortex
When the team artificially stimulated just twenty carefully selected early-onset cells that exhibited elevated firing levels immediately before animals executed a newly learned action, the intervention triggered both the larger pattern of brain activity associated with the learned movement and, in many instances, the movement itself.
Takaki Komiyama noted the surprising power small ensembles hold over the wider motor network, given that small-scale stimulation of a minute fraction of cells proved capable of driving specific large-scale behavior in a mammalian brain.
Brain State Dependency and Future Directions in the Komiyama Lab
Success depended heavily on the state of the motor cortex immediately before stimulation and whether the test subject was actively engaged with the task, as the experiments revealed that artificial activation is not a universal trigger on its own.
Investigators hope that deciphering this circuit logic could eventually aid in the development of brain-computer interfaces to help stroke and paralysis patients recover daily life activities, as well as inform future methods for promoting learning and restoring memory, while research continues in the Komiyama Lab with a follow-up project aimed at mapping the connections between these key neurons to understand how they coordinate to produce learned behavior.
