Fine-tuning optogenetics



ChR2 targeted to the axon initial segment

targeted ChR2

How can we know the functional roles of particular populations of neurons in the brain? Optogenetics is the 2010 “Method of the Year” selection at Nature Methods. One use of optogenetics is to stimulate the production of action potentials in a specified population of neurons by using a light source. One optogenetic tool used in this way is channelrhodopsin-2 (ChR2). When light activates the ChR2 protein its ion channel opens, neurons depolarize and action potentials can be initiated. As shown in the image to the right, the expression of ChR2 can be targeted to axon initial segments by using part of the Nav1.2 amino acid sequence (1).

Often optogenetic tools like ChR2 are expressed indiscriminately in neurons (lower panel in the image to right). Since neurons can communicate in several ways, including via gap junctions and signaling molecules such as nitric oxide, it would be nice to be able to precisely control action potential production in neurons, for example, specifically producing them only in axons.

Unfortunately, Grubb and Burrone were not able to demonstrate light-stimulated action potentials in their cultured neurons. I wonder if they would have better luck in living mouse brain where the neuron’s might express higher levels of their axon-targeted ChR2 protein.

2012 update. “Optogenetic stimulation of a hippocampal engram activates fear memory recall” – commentary about this research (similar study with another method)

Related reading.

Researchers Rouse Brain Cells that Control Eating Behavior in Mice

Toward the Second Generation of Optogenetic Tools

Drug-Driven AMPA Receptor Redistribution Mimicked by Selective Dopamine Neuron Stimulation

Image credits. copyright Grubb & Burrone, from Figure 1 in “Channelrhodopsin-2 Localised to the Axon Initial Segment“, an open-access article distributed under the terms of the Creative Commons Attribution License


About johnwschmidt

Exploring medical physiology.
This entry was posted in electrophysiology, Nav1.2 and tagged , , . Bookmark the permalink.

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