Primate cortex yields to cell class-specific functional imaging

An important question in brain research is how neurons and the circuits they form process information to produce behavior. To understand what happens in a human brain, it is necessary to study a brain of similar complexity, such as that of a primate. Examining how the neurons in a brain region called the visual cortex process information about what we see is especially informative. This is because animals can be taught to perform different visual tasks, and because the visual cortex is relatively easy to access. In principle, therefore, it should be possible to use modern genetic and imaging techniques to study the primate visual system, but until now, that has not been the case.

HFSP Program Grant holder Boris Zemelman and colleagues
authored on Thu, 08 December 2016

Like much of the brain, the visual cortex consists of different classes of neurons that can excite, inhibit or modulate the activity of neighboring neurons. One way to study how these different classes of neurons interact with each other is to alter the animal’s DNA, such that only one cell type stands out during the experiment, allowing its role in the brain to be closely monitored. This technique has been used to study the interactions among neurons in the rodent brain, because rodent DNA is easy to alter. However, it is not easy to manipulate primate DNA.

Seidemann et al. have, therefore, developed a new technique that can target a specific class of neurons, allowing the activity of just these cells to be distinguished from the rest. The breakthrough method, perfected under the support of a Human Frontier Science Program grant, uses specially designed harmless viruses to produce foreign proteins in the excitatory neurons of the visual cortex in an adult macaque. The optical properties of the proteins change when the neuron they are in is active, allowing the activity of the excitatory neurons to be detected and tracked in awake animals while they perform a visual task.

Previously, the activity of neurons in the primate visual cortex could only be measured using dyes that indiscriminately reported the activity of all the neurons present. Seidemann et al. found that, in addition to being more selective than the dye-based method, the new technique also more accurately depicted neuronal action potentials, which are the primary units of information in the brain.

Seidemann et al. now plan to use a similar method to study the activity of the inhibitory neurons of the primate visual cortex. Further examination of both excitatory and inhibitory neurons at much higher magnification, using a different microscopy technique, will also reveal more subtle features of their responses during visual tasks.


Calcium imaging with genetically encoded indicators in behaving primates. Eyal Seidemann, Yuzhi Chen, Yoon Bai, Spencer C Chen, Preeti Mehta, Bridget L Kajs, Wilson S Geisler, Boris V Zemelman. DOI: Published July 21, 2016, eLife 2016;5:e16178.

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