Leland Stanford Junior University

Circuit Therapeutics, Inc.

Humboldt-Universität Zu Berlin

Circuit Therapeutic, Inc.

Karl A Deisseroth

Feng Zhang

Viviana Gradinaru

Edward Stuart Boyden

M Bret Schneider

Peter Hegemann

Ofer Yizhar

Scott Delp

Lief Fenno

Andre Berndt

Jin Hyung Lee

Dan E Andersen

Raag D Airan

Charu Ramakrishnan

Lisa Gunaydin

Samuel J Yang

William E Allen

Isaac V Kauvar

Matthias Prigge

David Jacob Mishelevich

David Charles Lundmark

Alexander K Arrow

Michael E Llewellyn

Fred Moll

Li Ye

Christine A McLeavey Payne

Soo Yeun Lee

Jaimie M Henderson

Polina Olegovna Anikeeva

Brian Hsueh

Logan Grosenick

Noy Cohen

Marc Stewart Levoy

Alexander Jueshyan Yeh

Ada Shuk Yan Poon

Gordon Wetzstein

Yuji Tanabe

Kwanghun Chung

Robert C Malenka

David Moore

Jennifer McNab

Greg Stahler

Joyce Huang

Kay Tye

Leslie A Meltzer

Shrivats Mohan Iyer

Emily L Sylwestrak

Priya Rajasethupathy

Emily Anne Ferenczi

Matthew Wright

Christina K Kim

Raju Tomer

Alexander Aravanis

John S Y Ho

Aaron S Andalman

Susumu Yoshizawa

Michael J Broxton

Sung-Yon Kim

Masatoshi Inoue

Qiyuan Tian

James Marshel

Yoon Kim

Hideaki Kato

Tim Machado

Xiao Wang

Elizabeth R Aden

Kate L Montgomery

Sean Quirin

Vivien Tsao

Kelly Zalocusky

Kathryn L Montgomery

Avishek Adhikari

Christopher Towne

Inbal Goshen

Albrecht Stroh

Ilana Witten

Ethan B Richman

Vikaas Sohal

Scott L Delp

Frederic Moll

Bret Schneider

Provided herein are devices, methods, and systems for in situ gene sequencing of a target nucleic acid in a cell in an intact tissue. Methods of screening a candidate agent to determine whether the candidate agent modulates gene expression of a nucleic acid in a cell in an intact tissue are also provided herein.

Method of in situ gene sequencing

The present disclosure provides light-responsive polypeptides, and nucleic acids comprising nucleotide sequences encoding the light-responsive polypeptides. The present disclosure provides methods, devices, and systems for controlling the activity of a cell expressing a light-responsive polypeptide of the present disclosure.

Light-responsive polypeptides and methods of use thereof

Methods, kits, and systems for fixation of RNA permitting its detection in intact tissue, such as, large volume of mammalian tissue are disclosed. The methods, kits, and systems util-ize carbodiimide-based chemistry to stably retain RNAs in tissue clarified using CLARITY. Also provided herein are methods, kits, and systems for detection of RNAs ire clarified tissue.

RNA fixation and detection in CLARITY-based hydrogel tissue

Provided herein is a macroscope comprising an objective apparatus comprising a multifocal widefield optics comprising a plurality of optical components configured to focus on a plurality of planes. Also provided herein are methods for analyzing a three-dimensional specimen, the method comprising obtaining, via a macroscope, synchronous multifocal optical images of a plurality of planes of the three-dimensional specimen, wherein the macroscope comprises an objective apparatus comprising a multifocal widefield optics comprising a plurality of optical components configured to focus on a plurality of planes. The three-dimensional specimen can be a biological specimen, such as brain.

Multifocal macroscope for large field of view imaging of dynamic specimens

The present disclosure provides variant light-responsive polypeptides, and nucleic acids comprising nucleotide sequences encoding the light-responsive polypeptides. The present disclosure provides methods, devices, and systems for controlling the activity of a cell expressing a variant light-responsive polypeptide of the present disclosure.

Methods for selectively stimulating a plurality of light-responsive neurons in a sample are provided. Methods according to certain embodiments include irradiating a sample comprising a plurality of light-responsive neurons with a plurality of holographic images that are each configured to stimulate one or more light-responsive neurons in the sample, wherein the holographic images are created by light projection system that includes a plurality of light sources; a plurality of optical adjustment components; a plurality of spatial light modulators; a controller; a processor; and a computer-readable medium comprising instructions that, when executed by the processor, cause the controller to operate the light sources, optical adjustment components and spatial light modulators to generate and display a plurality of holographic images; direct each of the holographic images to a projection location; and project the holographic images onto the sample at a rate greater than 1 kHz. Light projection systems for irradiating a sample having light-responsive neurons with holographic images are also described.

Methods for temporal and spatial multiplexing of spatial light modulators and systems for same

The present disclosure provides methods of preparing a biological specimen for imaging analysis, comprising fixing and clearing the biological specimen and subsequently analyzing the cleared biological specimen using microscopy. Also included are methods of quantifying cells, for example, active populations of cells in response to a stimulant. The present disclosure also provides devices for practicing the described methods. A flow-assisted clearing device provides rapid clearing of hydrogel-embedded biological specimens without the need of specialized equipment such as electrophoresis or perfusion devices.

Method and system for imaging and analysis of a biological specimen

The present disclosure provides a genetically encoded calcium indicator (GECI), nucleic acids encoding the GECI, and host cells comprising the GECI. The present disclosure also provides methods of detecting a change in the intracellular concentration of a cell expressing a GECI of the present disclosure.

Calcium indicator polypeptides and methods of use thereof

The present disclosure provides optical image acquisition methods and devices for microscopy systems that enhance the field-of-view during image acquisition. According to aspects of the present disclosure, the methods and devices for enhancing the field-of-view of a sample during image acquisition in an optical imaging system include directing an incident electromagnetic field through a plurality of polarization-selective gratings, where each of the polarization-selective gratings is configured to apply a discrete amount of angular displacement to the incident electromagnetic field in a direction transverse or axial to the optical system's electromagnetic axis, resulting in an enhanced field-of-view during image acquisition.

Modular, electro-optical device for increasing the imaging field of view using time-sequential capture

Methods, kits, and systems for fixation of RNA permitting its detection in intact tissue, such as, large volume of mammalian tissue are disclosed. The methods, kits, and systems utilize carbodiimide-based chemistry to stably retain RNAs in tissue clarified using CLARITY. Also provided herein are methods, kits, and systems for detection of RNAs in clarified tissue.

RNA fixation and detection in clarity-based hydrogel tissue

Provided herein is a method of optically recording neural activity in one or more regions of a target tissue. Also provided is a method of optically modulating the activity of a neural tissue. Further provided is a system that finds use in performing the present methods.

Method and systems for measuring neural activity

Provided herein are methods for the treatment of bladder dysfunction, including detrusor hyperreflexia and detrusor external sphincter dyssynergia, fecal incontinence, and/or sexual dysfunction in an individual via the use of stably expressed light-responsive opsin proteins capable of selective hyperpolarization or depolarization of the neural cells that innervate the muscles responsible for physiologic functioning of urinary bladder, external urinary sphincter, external anal sphincter, and the male and female genitalia.

Methods for treating neurogenic disorders of the pelvic floor

Various systems and methods are implemented for controlling stimulus of a cell. One such method is implemented for optical stimulation of a cell expressing an NpHR ion pump. The method includes the step of providing a sequence of stimuli to the cell. Each stimulus increases the probability of depolarization events occurring in the cell. Light is provided to the cell to activate the expressed NpHR ion pump, thereby decreasing the probability of depolarization events occurring in the cell.

System for optical stimulation of target cells

The present disclosure provides methods of modulating a feature of a behavioral state. The methods involve inhibiting or activating the activity of a bed nucleus of stria terminalis (BNST) neuron, a BNST subnucleus, or a neuronal output to or from a BNST neuron. Animals encounter environmental conditions that require rapid switching among different behavioral states to increase the likelihood of survival and reproduction.

Optogenetic control of behavioral state

Growing community of inventors

Stanford, CA, United States of America

Karl A Deisseroth