GABA: A Novel Light-activated Probe
as a Neuroscience Research Tool
Princeton Docket #
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 GABAA 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 GABAA 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
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.
neuroscience research tool to study synaptic function at individual neurons and
screening with physiological realism.
Minimized GABAA antagonist
Improved spatial resolution over
conventional caged GABA.
Better Shelf Stability.
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
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
Intellectual Property & Development
protection is pending.
Princeton is currently seeking commercial partners
for the further development and commercialization of this opportunity.
TzodikovPrinceton University Office of Technology Licensing
University Office of Technology Licensing