Photorelease of GABA with Visible Light Using an Inorganic Caging Group

We describe the selective photorelease of γ-amino butyric acid (GABA) with a novel caged-GABA compound that uses a ruthenium complex as photosensor. This compound (“RuBi-GABA”) can be excited with visible wavelengths, providing greater tissue penetration, less photo-toxicity, and faster photorelease kinetics than currently used UV light-sensitive caged compounds. Using pyramidal neurons from neocortical brain slices, we show that RuBi-GABA uncaging induces GABA-A receptor-mediated responses, has no detectable side effects on endogenous GABAergic and glutamatergic receptors and generates responses with kinetics and spatial resolution comparable to the best caged GABA compounds presently available. Finally, we illustrate two potential applications of RuBi-GABA uncaging: GABA receptor mapping, and optical silencing of neuronal firing.

[1]  M Canepari,et al.  Photochemical and pharmacological evaluation of 7-nitroindolinyl-and 4-methoxy-7-nitroindolinyl-amino acids as novel, fast caged neurotransmitters , 2001, Journal of Neuroscience Methods.

[2]  Roberto Etchenique,et al.  A new strategy for neurochemical photodelivery: metal-ligand heterolytic cleavage. , 2003, Journal of the American Chemical Society.

[3]  E. Callaway,et al.  Photostimulation using caged glutamate reveals functional circuitry in living brain slices. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[4]  P. Schwartzkroin,et al.  Effects of GABA on CA3 pyramidal cell dendrites in rabbit hippocampal slices , 1988, Brain Research.

[5]  L. O. Svaasand,et al.  OPTICAL PROPERTIES OF HUMAN BRAIN , 1983, Photochemistry and photobiology.

[6]  K. Kaila,et al.  Posttetanic excitation mediated by GABA(A) receptors in rat CA1 pyramidal neurons. , 1997, Journal of neurophysiology.

[7]  G. Tamás,et al.  Excitatory Effect of GABAergic Axo-Axonic Cells in Cortical Microcircuits , 2006, Science.

[8]  Y. Ben-Ari,et al.  Giant synaptic potentials in immature rat CA3 hippocampal neurones. , 1989, The Journal of physiology.

[9]  S. Rothman,et al.  Optical suppression of seizure-like activity with an LED , 2007, Epilepsy Research.

[10]  L. Mullenders,et al.  Nucleotide excision repair in differentiated cells. , 2007, Mutation research.

[11]  G. Stuart,et al.  Excitatory Actions of GABA in the Cortex , 2003, Neuron.

[12]  B. Gähwiler,et al.  Activity-dependent disinhibition. I. Repetitive stimulation reduces IPSP driving force and conductance in the hippocampus in vitro. , 1989, Journal of neurophysiology.

[13]  Vincenzo Balzani,et al.  Photochemistry of coordination compounds , 1970 .

[14]  G. Augustine,et al.  Distribution of functional glutamate and GABA receptors on hippocampal pyramidal cells and interneurons. , 2000, Journal of neurophysiology.

[15]  H. Monyer,et al.  GABAergic Excitation in the Basolateral Amygdala , 2006, The Journal of Neuroscience.

[16]  Feng Zhang,et al.  Multimodal fast optical interrogation of neural circuitry , 2007, Nature.

[17]  George J Augustine,et al.  Chemical Two-Photon Uncaging: a Novel Approach to Mapping Glutamate Receptors , 1997, Neuron.

[18]  G. Fowles,et al.  Introduction to modern optics , 1968 .

[19]  E. Callaway,et al.  Excitatory cortical neurons form fine-scale functional networks , 2005, Nature.

[20]  J. Corrie,et al.  Comparative analysis of inhibitory effects of caged ligands for the NMDA receptor , 2005, Journal of Neuroscience Methods.

[21]  H. Markram,et al.  Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex. , 2000, Science.

[22]  Karel Svoboda,et al.  Circuit Analysis of Experience-Dependent Plasticity in the Developing Rat Barrel Cortex , 2003, Neuron.

[23]  H. Hönigsmann,et al.  Stress proteins in the cellular response to ultraviolet radiation. , 1996, Journal of photochemistry and photobiology. B, Biology.

[24]  J. Nadler,et al.  γ-Aminobutyrate, α-carboxy-2-nitrobenzyl ester selectively blocks inhibitory synaptic transmission in rat dentate gyrus , 2000 .

[25]  R. Etchenique,et al.  Ruthenium(II) bipyridyl complexes as photolabile caging groups for amines. , 2006, Inorganic chemistry.

[26]  M. Fagiolini,et al.  Optimization of Somatic Inhibition at Critical Period Onset in Mouse Visual Cortex , 2007, Neuron.

[27]  Roberto Etchenique,et al.  A New Inorganic Photolabile Protecting Group for Highly Efficient Visible Light GABA Uncaging , 2007, Chembiochem : a European journal of chemical biology.

[28]  S. Wang,et al.  Confocal imaging and local photolysis of caged compounds: Dual probes of synaptic function , 1995, Neuron.

[29]  B. Connors,et al.  Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor‐mediated responses in neocortex of rat and cat. , 1988, The Journal of physiology.

[30]  Karel Svoboda,et al.  Precise Development of Functional and Anatomical Columns in the Neocortex , 2004, Neuron.

[31]  R. Yuste,et al.  Two-photon uncaging of neurochemicals using inorganic metal complexes. , 2005, Chemical communications.

[32]  Juha Voipio,et al.  GABAergic Depolarization of the Axon Initial Segment in Cortical Principal Neurons Is Caused by the Na–K–2Cl Cotransporter NKCC1 , 2008, The Journal of Neuroscience.

[33]  B. Connors,et al.  Two networks of electrically coupled inhibitory neurons in neocortex , 1999, Nature.

[34]  P. Andersen,et al.  Two different responses of hippocampal pyramidal cells to application of gamma‐amino butyric acid. , 1980, The Journal of physiology.

[35]  R. Nicoll,et al.  GABA-mediated biphasic inhibitory responses in hippocampus , 1979, Nature.

[36]  Y. Ben-Ari Excitatory actions of gaba during development: the nature of the nurture , 2002, Nature Reviews Neuroscience.