Editors' ChoiceNeuroscience

Optogenetic Inhibition

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Science Signaling  29 Apr 2014:
Vol. 7, Issue 323, pp. ec118
DOI: 10.1126/scisignal.2005425

Optogenetic techniques that exploit light-gated ion channels, such as algal channelrhodopsins, can be used to reversibly manipulate neuronal excitability. When activated by light, channelrhodopsins allow cations to flow into the cell, thus depolarizing the cell and triggering an action potential. Ectopic expression of channelrhodopsins in specific neurons allows researchers to conveniently and efficiently activate neurons at will. However, it has proven more difficult to inhibit neurons using optogenetic techniques. Existing tools for optogenetically inhibiting neurons rely on light-activated pumps that bring anions into the neurons or remove protons from the neurons, but these tools are not efficient, because only one anion or proton is pumped per photon of light. In contrast, light-gated channels are open to continuous ion flow in the presence of light. Wietek et al. and Berndt et al. have engineered channelrhodopsins that allow chloride anions to flow into cells when activated by light, thus hyperpolarizing the cells and inhibiting action potentials. These new tools should allow researchers to optogenetically inhibit neurons as easily and efficiently as they can activate them (see Hayashi).

J. Wietek, J. S. Wiegert, N. Adeishvili, F. Schneider, H. Watanabe, S. P. Tsunoda, A. Vogt, M. Elstner, T. G. Oertner, P. Hegemann, Conversion of channelrhodopsin into a light-gated chloride channel. Science 344, 409–412 (2014). [Abstract] [Full Text]

A. Berndt, S. Y. Lee, C. Ramakrishnan, K. Deisseroth, Structure-guided transformation of channelrhodopsin into a light-activated chloride channel. Science 344, 420–424 (2014). [Abstract] [Full Text]

S. Hayashi, Silencing neurons with light. Science 344, 369–370 (2014). [Abstract] [Full Text]