Double-Caged GABA: A Novel Light-Activated Probe as a Neuroscience Research Tool

Double-caged GABA:  A Novel Light-activated Probe as a Neuroscience Research Tool

Princeton Docket # 13-2896-1

Researchers at Princeton University, Departments of Molecular Biology and Chemistry, have developed a light-activated probe that can be used as a neuroscience research tool.

                Current methods of probing neural activity such as microelectrode stimulation are limited by the invasiveness of inserting probes, but optical methods offer a powerful noninvasive alternative. Of optical methods, ¿caged compounds¿ have emerged as an improved technique for achieving rapid, high-resolution neural stimulation. Caged compounds are neurotransmitters synthetically modified to contain a photoactive protecting group (cage), which undergoes autocleavage upon light exposure. Though caged versions of neurotransmitters such as glutamate have been successfully used in brain slices, previously developed forms of caged GABA have largely been shown to be antagonists for GABA_A receptors, which have greatly limited their application. In order to minimize this antagonistic effect, researchers at Princeton University have synthesized double-caged GABA to address this problem.

               Double-caged GABA is photoprotected at two functional groups. There are two advantages of the double-caged GABA. First, the bis-caged GABA exhibits significantly less antagonism for GABA_A receptors, while still uncaging with rapid kinetics. Second, double-caging results in a square relationship between light exposure and GABA release, conferring the added benefit of improved spatial resolution similar to that of two-photon excitation. Therefore, double-caged GABA is a novel caged compound that significantly improves upon previous forms of caged GABA while also maintaining high spatial resolution.

It is anticipated that this novel probe can be applied to study synaptic connectivity and function at the level of the individual neuron. A future application of this probe is high-throughput screening of GABA receptor function. Another future application is focal stimulation in vivo with therapeutic and research potential.

Applications

Advantages

·         Minimized GABA_A antagonist effect.

·         Improved spatial resolution over conventional caged GABA.

·         Better Shelf Stability.

The Faculty Inventor

Samuel S.-H. Wang is an Associate Professor of Molecular Biology. The Wang laboratory does basic research in several areas: (1) information processing in the cerebellum, including its contributions to motor learning; (2) cerebellar roles in cognitive and affective function and autism spectrum disorder; (3) the improvement of tools for awake, in vivo optical imaging; and (4) synaptic learning rules throughout the brain. The Wang Lab applies advanced methods to the optical control and imaging of brain activity. Dr. Wang¿s outstanding achievements have been recognized by several prestigious organizations. Dr. Wang received the McKnight Foundation Technological Innovations Award in 2012; he joined Rita Allen Foundation Board in 2010; and his first book, Welcome to Your Brain, is a recipient of the American Association for the Advancement of Science/Subaru SB&F Prize for Excellence in Science Books in 2009.

Martin F. Semmelhack  is a Professor of Chemistry. Martin F Semmelhack Laboratory is focused on the application of organic chemistry to solve problems in biology. Areas of interest include: the chemistry of bacterial signaling, isolation and structure determination of new signaling molecules, synthesis of the signals and analog structures, and evaluation of their biological activity. Dr. Semmelhack has served on the editorial board of the Journal of Organic Chemistry, Organometallics, Organic Reactions, and Organic Synthesis (editor of vol 62), and edited volume IV of Comprehensive Organic Synthesis.

Intellectual Property & Development status

Patent protection is pending.

Princeton is currently seeking commercial partners for the further development and commercialization of this opportunity.

Contact:

Laurie Tzodikov
Princeton University Office of Technology Licensing

(609) 258-7256  tzodikov@princeton.edu

Wenting Luo

Princeton University Office of Technology Licensing

(609) 258-5579  wluo@princeton.edu