Rafael Yuste, MD, PhD

• Co-Director, Kavli Institute for Brain Science

Neural Circuits and Ensembles

Neural Circuits and Ensembles

The goal of our laboratory is to decipher the neural code, i.e., the relation between the activity of neurons and behavior or mental states, by understanding the function of the neural circuits.

Why focus on neural circuits? For over a century, the neuron doctrine — which states that the neuron is the structural and functional unit of the nervous system — has provided a conceptual foundation for neuroscience. This viewpoint reflects its origins in a time when the use of single-neuron anatomical and physiological techniques was prominent. However, recent multineuronal recording methods have revealed that groups of neurons, rather than individual cells, can form physiological units and may generate emergent properties and functional states. The focus on the emergent properties of neural networks is a new paradigm for neuroscience, and can incorporate knowledge acquired with single-neuron approaches and go beyond them, helping us understand how emergent functional states generate behavior, cognition and mental disease.

We are testing the hypothesis that neuronal circuits generate emergent functional properties using electrophysiology and a variety of optical methods, some of which we have helped develop, like calcium imaging, two-photon imaging, two-photon uncaging, two-photon optogenetics and holographic microscopy. In particular, we are studying the role of coactive groups of neurons, known as neuronal ensembles (“attractors”) in mouse visual cortex. The cortex is the larger part of the brain in mammals and is the primary site of mental functions like perception, memory, control of voluntary movements, imagination, language, art and music. Cortical ensembles, which can be activated spontaneously, could be functional building blocks of cortical circuits and, as such, may represent the physical implementation of mental processes such as perceptions, memories or thoughts. Because of this, we are also interested in the possible role of altered neuronal ensembles in the pathophysiology of mental and neurological diseases.

In addition, we are studying neuronal ensembles in the nerve net of the small cnidarian Hydra vulgaris. Hydra has a simple nervous system in which one can measure the activity of all of its neurons during behavior, so it could be an ideal preparation to decipher neural codes. Similarly to the genetic code, it is conceivable that the neural code and basic principles of neural circuit function could be conserved throughout evolution.