How do Brain Functions Arise? Using Lasers for Brain Control

In our lab research, we are interested in understanding how the coordinated activity of groups of neurons, known as neuronal assemblies, allows us to interpret sensory stimuli, generate perceptions, create memories, and make movements. The question of how brain functions arise has been the subject of countless philosophical and scientific debates for hundreds of years. But recently, thanks to the development of various technologies that allow us to see and modify the activity of hundreds of neurons, it has been possible to begin to understand the role of neuronal assemblies in different brain functions.

For example, a person who practices martial arts, after years of training, generates in their brain a model of the outside world and based on this model controls movements to be able to attack and defend efficiently. Similarly, a person who plays the cello represents different musical notes in their brain to be able to execute precise movements during a concert following an internally generated rhythm.

In this way, the execution of movements learned through hundreds of repetitions is given by the sequential activation of neural assemblies found in brain nuclei related to motor control.

To explain how neural assemblies are formed, Donald Hebb proposed that repeated activation of the same neurons would increase connectivity between them, generating highly efficient patterns of activity, such as the stereotyped movements of a martial artist or a cellist. Hebb’s postulates represented a change in the paradigm of neuroscience: brain functioning began to be understood in terms of groups of neurons with coordinated activity that are responsible for various brain functions.

To study in the lab the relationship between the activity of neuronal assemblies and various brain functions we use techniques that allow us to visualize and manipulate neuronal activity with light, such as double-photon microscopy, optogenetics, and photopharmacology. These frontier techniques are redefining neurosciences as they allow brain activity to be read and write to control different behaviors.

To understand the operation principle of these techniques, we can think of a neuron as a sphere whose surface is the neuronal outer membrane. This surface has proteins inserted to form channels that allow the flow of different ions, such as sodium, potassium, and calcium, among others. The flow of ions across the cell membrane generates the electrical activity of neurons. Using genetically encoded fluorescent indicators, it is possible to see, through flashes of light, when neurons have electrical activity. It is also possible to insert artificial channels into neurons that allow them to be activated using lasers; this technique is known as optogenetics. Finally, photopharmacology consists of the release of neuromodulators or neurotransmitters with light in very high spatial and temporal resolution.

Five years ago, in collaboration with Columbia University, New York, United States, we published a paper (Carrillo-Reid et al., 2019) on our use of double-photon microscopy and artificial intelligence techniques to control the perception of mice by punctually activating neurons in the primary visual cortex. With these experiments we showed that activating a neural assembly by lasers could evoke images in the brain.

We have recently used photopharmacology to study the effect of controlled release of dopamine through light in different brain nuclei (Velázquez-Delgado et al., 2024; Zamora-Ursulo et al., 2023). This is important because in Parkinson’s disease neurons that normally produce dopamine cease to exist. Because of this, patients take medications that increase dopamine levels in a sustained manner throughout the brain, which causes the appearance of involuntary movements known as dyskinesias. Our experiments showed that in an animal model of the Parkinson’s disease, the release of dopamine through light in a single brain nucleus related to movement control had the same effects as the drugs normally used, but without causing dyskinesias, which suggests that in the long-term, photopharmacology could be an option for treating the disease, reducing the unwanted effects intrinsic to traditional pharmacology.

The importance of our research projects lies in the fact that it is known that the activity of certain neuronal assemblies is altered in diseases such as Parkinson’s and Alzheimer’s, schizophrenia, and even depression, in such a way that, if we are able to reprogram the activity of these groups of neurons with lasers, we would have the ability to restore normal behavior in patients.

These experiments open doors to understanding the rules of reprogramming neural circuits, which could allow the creation, maintenance, and remodeling of neural assemblies in pathological conditions. Future applications of these projects could be extended to the treatment of different neurological disorders with an unprecedented precision level. However, it is important to note that all these techniques are still in research stages and many years of studies remain before they can be applied in the clinic.

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