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Somatosensory microcircuits for real-world hand function

Background

A central goal of systems neuroscience is to understand how real world behaviour, such as hand movements and use, is generated by coordinated populations of single neurons. Currently, the main approach for tackling this problem is single-cell electrophysiology, where the electrical activity of one to a few hundred neurons is measured while a subject is performing some experimental task.

The Problem

Electrophysiology is incredibly informative but it has several important limitations. First, neurons are sampled very sparsely and we cannot differentiate neuronal cell-types or layers. This means the measurements can only provide limited insight into the organization of these populations of neurons. Second, long-term observation of the same neurons is difficult because there is no definitive way to confirm whether the same neurons are being recorded from session to session.

Electrical activity in neurons is always accompanied by an influx of calcium ions. By measuring those calcium ions, we can determine when neurons are active. Calcium imaging is a microscopy technique that can do this. When using a two-photon microscope, it can provide dense and long-term recordings from neuronal populations with sufficient resolution to differentiate between cell-types and between neuronal layers.

The Project

Two-photon calcium imaging is already well-established in flies, fish and rodents, and is providing truly revolutionary insight into the neural basis of animal behaviour. Our critical foundational milestone is applying two-photon microscopy to NHP subjects while performing hand function tasks, given their higher brain complexity and translation potential to the human brain.

We will publish and share our design algorithms and approaches in an open-access manner, so that others around the world can rapidly implement them in their labs. Achieving our foundational milestone will open up research avenues for many researchers, who will be able to immediately leverage our technical work for their scientific aims and brain areas of interest. Our success here will also enable us to explore an important new scientific direction: determining the microscale organization of the somatosensory cortex, the region of the brain that receives and processes sensory information from the entire body, and how it changes after nerve damage. Using two-photon imaging we will be able to precisely monitor and understand changes in the brain that follow nerve injury and repair, along with rehabilitation interventions, in the hopes of identifying those changes that lead to positive outcomes.

Western Researchers Andrew Pruszynski Julio Martinez-Trujillio Stefan Everling Brian Corneil Vaishnavi Sukumar Rhonda Kersten

HHMI Researchers Adam Hantman

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