Leland Stanford Junior University

Max-planck-gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

Humboldt-universität Zu Berlin

Peter Hegemann

Karl A Deisseroth

Ofer Yizhar

Andre Berndt

Lisa Gunaydin

Lief Fenno

Matthias Prigge

Ernst Bamberg

Georg Nagel

Emily Anne Ferenczi

Aspects of the disclosure include devices, systems and methods for optogenetic modulation of action potentials in target cells. The subject devices include light-generating devices, control devices, and delivery devices for delivering vectors to target cells. The subject systems include light-activated proteins, response proteins, nucleic acids comprising nucleotide sequences encoding these proteins, as well as expression systems that facilitate expression of these proteins in target cells. Also provided are methods of using the subject devices and systems to optogenetically inhibit and intercept action potentials in target cells, e.g., to treat a neurological or psychiatric condition in a human or non-human animal subject.

Devices, systems and methods for optogenetic modulation of action potentials in target cells

Provided herein are compositions comprising light-activated chimeric proteins expressed on plasma membranes and methods of using the same to selectively depolarize excitatory or inhibitory neurons.

Light-activated chimeric opsins and methods of using the same

Stimulation of target cells using light, e.g., in vivo or in vitro, is implemented using a variety of methods and devices. One example involves a vector for delivering a light-activated molecule comprising a nucleic acid sequence that codes for light-activated molecule. The light-activated molecule includes a modification to a location near the all-trans retinal Schiff base, e.g., to extends the duration time of the open state. Other aspects and embodiments are directed to systems, methods, kits, compositions of matter and molecules for ion channels or pumps or for controlling currents in a cell (e.g., in in vivo and in vitro environments).

Optically-based stimulation of target cells and modifications thereto

Stimulation of target cells using light, e.g., in vivo or in vitro, is implemented using a variety of methods and devices. One example involves a vector for delivering a light-activated molecule comprising a nucleic acid sequence that codes for light-activated molecule. The light-activated molecule includes a modification to a location near the all-trans retinal Schiff base, e.g., to extends the duration time of the open state. Other aspects and embodiments are directed to systems, methods, kits, compositions of matter and molecules for ion channels or pumps or for controlling currents in a cell (e.g., in vivo or in vitro environments).

A biological photoreceptor, which is a directly light-controlled ion channel, including (i) an apoprotein and (ii) a light-sensitive polyene covalently bound to the apoprotein, the polyene interacting with the apoprotein and functioning as a direct light-sensitive gate.

Use of biological photoreceptors as directly light-activated ion channels

Use of a biological photoreceptor as light-controlled ion channel for the alteration of the ion conductivity of a membrane by means of light. The photoreceptor used comprises an apoprotein and a light-sensitive polyene covalently bound to the apoprotein, said polyene interacting with the apoprotein and functioning as a light-sensitive gate.

The invention is directed to a method for altering the ion conductivity of a membrane. The method comprises inserting a biological photoreceptor into the membrane. The biological photoreceptor is configured to act as a light-controlled ion channel. The photoreceptor used comprises an apoprotein and a light-sensitive polyene covalently bound to the apoprotein, wherein the polyene interacts with the apoprotein and functions as a light-sensitive gate.

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Falkensee, Germany

Peter Hegemann