Otis, Thomas

Titles

Professor, and Chair, Neurobiology

Chair, Neurobiology

Contact Information

Email
otist@ucla.edu
Phone
Lab Number: (310) 206-5274
Office Phone Number: (310) 206-0746
Address

Work Address:

Laboratory
CHS 63-241
Los Angeles, CA 90095
UNITED STATES
Office
CHS 63-241
Los Angeles, CA 90095
UNITED STATES

Biography

Research Interest:

Cellular and molecular aspects of neural signaling

Our brains accomplish (or sometimes fail at) their jobs by generating coordinated patterns of electrical signals in groups of nerve cells (neurons). Research in my laboratory focuses on the general question of how this coordination occurs. Circuits, single connections (synapses) and electrical properties particular to individual neurons combine to allow large groups of neurons to generate the specific firing patterns that ultimately result in thoughts, feelings and behaviors. In an effort to understand how the brain works at such a nuts and bolts level, we concentrate mainly on the cerebellum, a brain region responsible for coordinating movement. The cerebellum is a principal brain area involved in learning how to make precise and sequenced movements such as are required for playing a musical instrument or excelling at a sport. Yet the cerebellum is critical for even ‘automatic’ movements such as postural adjustments to maintain balance or eye movements that allow redirection of gaze. Diseases of the cerebellum, collectively termed ataxias, degrade the ability to make coordinated movements and impair the formation of motor memories, memories that are necessary to improve coordination with practice. Our lab combines classical neurophysiological and advanced optical approaches to study how circuits of cerebellar neurons hone movements and store motor memories. Techniques include photolysis of caged compounds in intact brain circuits, optical manipulation of various photosensitive targets, patterned illumination for stimulating neuronal circuits, and diffraction-illuminated spot imaging of membrane potential from single neurons using optical voltage sensors. Recently we have developed an optogenetic approach to manipulate the activity of groups of cerebellar neurons and thereby evoke movements which can be studied with high speed video and motion tracking algorithms. By pairing specific patterns of neuronal activity with sensory stimuli one can experimentally induce the formation of new motor memories. These and related experiments allow us to test ideas about how memories are formed and stored, and also to interrogate cerebellar circuits in mouse models of ataxia in order to probe the circuit basis for these pathologies. Finally, in collaboration with Ben Novitch’s lab at UCLA and Clive Svendsen’s lab at Cedars Sinai we have been recording from stem cell derived motor neurons in order to understand fundamental mechanisms of motor neuron diseases and facilitate drug discovery to treat these disorders.

Publications

Peng, Z.; Zhang, N.; Wei, W.; Huang, C. S.; Cetina, Y.; Otis, T. S.; Houser, C. R.   A reorganized GABAergic circuit in a model of epilepsy: evidence from optogenetic labeling and stimulation of somatostatin interneurons J Neurosci, 2013; 33(36): 14392-405.
Santhakumar, V.; Meera, P.; Karakossian, M. H.; Otis, T. S.   A Reinforcing Circuit Action of Extrasynaptic GABAA Receptor Modulators on Cerebellar Granule Cell Inhibition Plos One, 2013; 8(8): e72976.
Hansen, S. T.; Meera, P.; Otis, T. S.; Pulst, S. M.   Changes in Purkinje cell firing and gene expression precede behavioral pathology in a mouse model of SCA2, Human Molecular Genetics, 2013; 22(2): 271-283.
Mathews, P. J.; Lee, K. H.; Peng, Z. C.; Houser, C. R.; Otis, T. S.   Effects of Climbing Fiber Driven Inhibition on Purkinje Neuron Spiking, Journal of Neuroscience, 2012; 32(50): 17988-17997.
Dellal, S. S.; Luo, R.; Otis, T. S.   GABA(A) receptors increase excitability and conduction velocity of cerebellar parallel fiber axons, Journal of Neurophysiology, 2012; 107(11): 2958-2970.
Otis, T. S.; Mathews, P. J.; Lee, K. H.; Maiz, J.   How do climbing fibers teach?, Frontiers in Neural Circuits, 2012; 6: .
Maiz, J.; Karakossian, M. H.; Pakaprot, N.; Robleto, K.; Thompson, R. F.; Otis, T. S.   Prolonging the postcomplex spike pause speeds eyeblink conditioning, Proceedings of the National Academy of Sciences of the United States of America, 2012; 109(41): 16726-16730.
Pulst, S. M.; Otis, T. S.   Repolarization Matters: Mutations in the Kv4.3 Potassium Channel Cause SCA19/22, Annals of Neurology, 2012; 72(6): 829-831.
Yue, L.; Pawlowski, M.; Dellal, S. S.; Xie, A.; Feng, F.; Otis, T. S.; Bruzik, K. S.; Qian, H. H.; Pepperberg, D. R.   Robust photoregulation of GABA(A) receptors by allosteric modulation with a propofol analogue, Nature Communications, 2012; 3: .
Gehman, L. T.; Meera, P.; Stoilov, P.; Shiue, L.; O'Brien, J. E.; Meisler, M. H.; Ares, M.; Otis, T. S.; Black, D. L.   The splicing regulator Rbfox2 is required for both cerebellar development and mature motor function, Genes & Development, 2012; 26(5): 445-460.
Fink, A. E.; Bender, K. J.; Trussell, L. O.; Otis, T. S.; DiGregorio, D. A.   Two-Photon Compatibility and Single-Voxel, Single-Trial Detection of Subthreshold Neuronal Activity by a Two-Component Optical Voltage Sensor, Plos One, 2012; 7(8): .
Hansen, S. T.; Meera, P.; Otis, T. S.; Pulst, S. M.   Changes in Purkinje Cell Firing Accompany Biochemical and Behavioral Changes in a Mouse Model of SCA 2, Neurology, 2011; 76(9): A346-A347.
Kruger, L.; Otis, T. S.; Shtrahman, M.   Golgi in retrospect: A historiographic examination of contextual influence in tracing the constructs of neuronal organization, Brain Research Reviews, 2011; 66(1-2): 68-74.
Meera, P.; Wallner, M.; Otis, T. S.   Molecular basis for the high THIP/gaboxadol sensitivity of extrasynaptic GABA(A) receptors, Journal of Neurophysiology, 2011; 106(4): 2057-2064.
Meera, P.; Olsen, R. W.; Otis, T. S.; Wallner, M.   Alcohol- and Alcohol Antagonist-Sensitive Human GABA(A) Receptors: Tracking delta Subunit Incorporation into Functional Receptors, Molecular Pharmacology, 2010; 78(5): 918-924.
Meera, P.; Olsen, R. W.; Otis, T. S.; Wallner, M.   GABA(A) RECEPTOR Delta SUBUNITS NOT ONLY CONFER HIGH SENSITIVITY TO ALCOHOL, BUT ALSO DRAMATICALLY INCREASE THIP/GABOXADOL SENSITIVITY, Alcoholism-Clinical and Experimental Research, 2010; 34(6): 194A-194A.
Wallner, M.; Meera, P.; Olsen, R. W.; Otis, T. S.   HIGH SENSITIVITY TO GABOXADOL AND ETHANOL OF delta SUBUNIT-CONTAINING GABA(A) RECEPTORS, Alcoholism-Clinical and Experimental Research, 2010; 34(8): 56A-56A.
Meera, P.; Olsen, R. W.; Otis, T. S.; Wallner, M.   THE GABA(A) RECEPTOR DELTA SUBUNIT NOT ONLY CONFERS HIGH SENSITIVITY TO ETOH, BUT ALSO DRAMATICALLY INCREASES THIP/GABOXADOL SENSITIVITY, Alcoholism-Clinical and Experimental Research, 2010; 34(8): 157A-157A.
Meera, P.; Olsen, R. W.; Otis, T. S.; Wallner, M.   Etomidate, propofol and the neurosteroid THDOC increase the GABA efficacy of recombinant alpha 4 beta 3 delta and alpha 4 beta 3 GABA(A) receptors expressed in HEK cells, Neuropharmacology, 2009; 56(1): 155-160.
Bradley, J.; Luo, R.; Otis, T. S.; DiGregorio, D. A.   Submillisecond Optical Reporting of Membrane Potential In Situ Using a Neuronal Tracer Dye, Journal of Neuroscience, 2009; 29(29): 9197-9209.
Otis, T. S.   Comments on "Ethanol sensitivity of GABAergic currents in cerebellar granule neurons is not increased by a single amino acid change (R100Q) in the alpha(6) GABA(A) receptor subunit", Journal of Pharmacology and Experimental Therapeutics, 2008; 324(1): 399-400.
Otis, T. S.; Sofroniew, M. V.   Glia get excited, Nature Neuroscience, 2008; 11(4): 379-380.
Lutz, C.; Otis, T. S.; DeSars, V.; Charpak, S.; DiGregorio, D. A.; Emiliani, V.   Holographic photolysis of caged neurotransmitters, Nature Methods, 2008; 5(9): 821-827.
Fortin, D. L.; Banghart, M. R.; Dunn, T. W.; Borges, K.; Wagenaar, D. A.; Gaudry, Q.; Karakossian, M. H.; Otis, T. S.; Kristan, W. B.; Trauner, D.; Kramer, R. H.   Photochemical control of endogenous ion channels and cellular excitability, Nature Methods, 2008; 5(4): 331-338.
Santhakumar, V.; Wallner, M.; Otis, T. S.   Ethanol acts directly on extrasynaptic subtypes of GABA(A) receptors to increase tonic inhibition, Alcohol, 2007; 41(3): 211-221.
Santhakumar, V.; Wallner, M.; Otis, T. S.   Ethanol acts directly on extrasynaptic subtypes of GABA(A) receptors to increase tonic inhibition (vol 41, pg 211, 2007), Alcohol, 2007; 41(6): 461-461.
Santhakumar, V.; Karakossian, M. H.; Otis, T. S.   Ethanol enhancement of GABA(A) receptor function in cerebellum, Alcoholism-Clinical and Experimental Research, 2007; 31(6): 290A-290A.
Kruger, L.; Otis, T. S.   Whither withered Golgi? A retrospective evaluation of reticularist and synaptic constructs, Brain Research Bulletin, 2007; 72(4-6): 201-207.
Breese, G. R.; Criswell, H. E.; Carta, M.; Dodson, P. D.; Hanchar, H. J.; Khisti, R. T.; Mameli, M.; Ming, Z.; Morrow, A. L.; Olsen, R. W.; Otis, T. S.; Parsons, L. H.; Penland, S. N.; Roberto, M.; Siggins, G. R.; Valenzuela, C. F.; Wallner, M.   Basis of the gabamimetic profile of ethanol, Alcoholism-Clinical and Experimental Research, 2006; 30(4): 731-744.
Otis, T. S.; Jen, J. C.   Blessed are the pacemakers, Nature Neuroscience, 2006; 9(3): 297-298.
Santhakumar, V.; Hanchar, H. J.; Wallner, M.; Olsen, R. W.; Otis, T. S.   Contributions of the GABA(A) receptor alpha 6 subunit to phasic and tonic inhibition revealed by a naturally occurring polymorphism in the alpha 6 gene, Journal of Neuroscience, 2006; 26(12): 3357-3364.
Hanchar, H. J.; Dodson, P. D.; Olsen, R. W.; Otis, T. S.; Wallner, M.   Alcohol-induced motor impairment caused by increased extrasynaptic GABA(A) receptor activity, Nature Neuroscience, 2005; 8(3): 339-345.
Meera, P.; Dodson, P. D.; Karakossian, M. H.; Otis, T. S.   Expression of GFP-tagged neuronal glutamate transporters in cerebellar Purkinje neurons, Neuropharmacology, 2005; 49(6): 883-889.
Otis, T. S.; Hanchar, H. J.; Dodson, P. D.; Olsen, R. W.; Wallner, M.   Letters to the Editor, Alcoholism-Clinical and Experimental Research, 2005; 29(7): 1358-1358.
Wallner, M.; Hanchar, H. J.; Dodson, P. D.; Otis, T. S.; Olsen, R. W.   Molecular actions of alcohol on extrasynaptic GABA(A) receptors, Journal of Neurochemistry, 2005; 94: 21-21.
Smith, S. L.; Otis, T. S.   Pattern-dependent, simultaneous plasticity differentially transforms the input-output relationship of a feedforward circuit, Proceedings of the National Academy of Sciences of the United States of America, 2005; 102(41): 14901-14906.
Wallner, M.; Hanchar, H. J.; Dodson, P.; Otis, T. S.; Olsen, R. W.   Role of 8 subunit-containing GABA(A) receptors in acute ethanol actions, Alcoholism-Clinical and Experimental Research, 2005; 29(5): 173A-173A.
Smith, S. L.; Judy, J. W.; Otis, T. S.   An ultra small array of electrodes for stimulating multiple inputs into a single neuron, Journal of Neuroscience Methods, 2004; 133(1-2): 109-114.
Karakossian, M. H.; Otis, T. S.   Excitation of cerebellar interneurons by group I metabotropic glutamate receptors, Journal of Neurophysiology, 2004; 92(3): 1558-1565.
Wallner, M.; Hanchar, H. J.; Otis, T. S.; Olsen, R. W.   Extrasynpatic GABA(A) receptors as mediators of low concentration ethanol effects, Alcoholism-Clinical and Experimental Research, 2004; 28(5): 92A-92A.
Otis, T. S.; Brasnjo, G.; Dzubay, J. A.; Pratap, M.   Interactions between glutamate transporters and metabotropic glutamate receptors at excitatory synapses in the cerebellar cortex, Neurochemistry International, 2004; 45(4): 537-544.
Brasnjo, G.; Otis, T. S.   Isolation of glutamate transport-coupled charge flux and estimation of glutamate uptake at the climbing fiber-Purkinje cell synapse, Proceedings of the National Academy of Sciences of the United States of America, 2004; 101(16): 6273-6278.
Hausser, M.; Raman, I. M.; Otis, T.; Smith, S. L.; Nelson, A.; du Lac, S.; Loewenstein, Y.; Mahon, S.; Pennartz, C.; Cohen, I.; Yarom, Y.   The beat goes on: Spontaneous firing in mammalian neuronal microcircuits, Journal of Neuroscience, 2004; 24(42): 9215-9219.
Brasnjo, G.; Otis, T. S.   Glycine transporters not only take out the garbage, they recycle, Neuron, 2003; 40(4): 667-669.
Smith, S. L.; Otis, T. S.   Persistent changes in spontaneous firing of Purkinje neurons triggered by the nitric oxide signaling cascade, Journal of Neuroscience, 2003; 23(2): 367-372.
Dzubay, J. A.; Otis, T. S.   Climbing fiber activation of metabotropic glutamate receptors on cerebellar Purkinje neurons, Neuron, 2002; 36(6): 1159-1167.
Otis, T. S.   Helping thy neighbors: Spillover at the mossy fiber glomerulus, Neuron, 2002; 35(3): 412-414.
Brasnjo, G.; Otis, T. S.   Neuronal glutamate transporters control activation of postsynaptic metabotropic glutamate receptors and influence cerebellar long-term depression, Neuron, 2001; 31(4): 607-616.
Otis, T. S.   Vesicular glutamate transporters in cognito, Neuron, 2001; 29(1): 11-14.
Otis, T. S.; Kavanaugh, M. P.   Isolation of current components and partial reaction cycles in the glial glutamate transporter EAAT2, Journal of Neuroscience, 2000; 20(8): 2749-2757.
Otis, T. S.; Jahr, C. E.   Anion currents and predicted glutamate flux through a neuronal glutamate transporter, Journal of Neuroscience, 1998; 18(18): 7099-7110.
Otis, T. S.; Kavanaugh, M. P.; Jahr, C. E.   Postsynaptic glutamate transport at the climbing fiber Purkinje cell synapse, Science, 1997; 277(5331): 1515-1518.
Otis, T. S.; Wu, Y. C.; Trussell, L. O.   Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites, Journal of Neuroscience, 1996; 16(5): 1634-1644.
Otis, T.; Zhang, S.; Trussell, L. O.   Direct measurement of AMPA receptor desensitization induced by glutamatergic synaptic transmission, Journal of Neuroscience, 1996; 16(23): 7496-7504.
Otis, T. S.; Trussell, L. O.   Inhibition of transmitter release shortens the duration of the excitatory synaptic current at a calyceal synapse, Journal of Neurophysiology, 1996; 76(5): 3584-3588.
Buhl, E. H.; Otis, T. S.; Mody, I.   Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy model, Science, 1996; 271(5247): 369-373.
Otis, T. S.; Raman, I. M.; Trussell, L. O.   AMPA RECEPTORS WITH HIGH CA2+ PERMEABILITY MEDIATE SYNAPTIC TRANSMISSION IN THE AVIAN AUDITORY PATHWAY, Journal of Physiology-London, 1995; 482(2): 309-315.
Mody, I.; Otis, T. S.; Bragin, A.; Hsu, M.; Buzsaki, G.   GABAERGIC INHIBITION OF GRANULE CELLS AND HILAR NEURONAL SYNCHRONY FOLLOWING ISCHEMIA-INDUCED HILAR NEURONAL LOSS, Neuroscience, 1995; 69(1): 139-150.
Mody, I.; De Koninck, Y.; Otis, T. S.; Soltesz, I.   BRIDGING THE CLEFT AT GABA SYNAPSES IN THE BRAIN, Trends in Neurosciences, 1994; 17(12): 517-525.
Otis, T. S.; De Koninck, Y.; Mody, I.   LASTING POTENTIATION OF INHIBITION IS ASSOCIATED WITH AN INCREASED NUMBER OF GAMMA-AMINOBUTYRIC-ACID TYPE-A RECEPTORS ACTIVATED DURING MINIATURE INHIBITORY POSTSYNAPTIC CURRENTS, Proceedings of the National Academy of Sciences of the United States of America, 1994; 91(16): 7698-7702.
Otis, T. S.; De Koninck, Y.; Mody, I.   CHARACTERIZATION OF SYNAPTICALLY ELICITED GABA-B RESPONSES USING PATCH-CLAMP RECORDINGS IN RAT HIPPOCAMPAL SLICES, Journal of Physiology-London, 1993; 463: 391-407.
Otis, T. S.; Mody, I.   DIFFERENTIAL ACTIVATION OF GABA-A AND GABA-B RECEPTORS BY SPONTANEOUSLY RELEASED TRANSMITTER, Journal of Neurophysiology, 1992; 67(1): 227-235.
Staley, K. J.; Otis, T. S.; Mody, I.   MEMBRANE-PROPERTIES OF DENTATE GYRUS GRANULE CELLS - COMPARISON OF SHARP MICROELECTRODE AND WHOLE-CELL RECORDINGS, Journal of Neurophysiology, 1992; 67(5): 1346-1358.
Otis, T. S.; Mody, I.   MODULATION OF DECAY KINETICS AND FREQUENCY OF GABA-A RECEPTOR-MEDIATED SPONTANEOUS INHIBITORY POSTSYNAPTIC CURRENTS IN HIPPOCAMPAL-NEURONS, Neuroscience, 1992; 49(1): 13-32.
Mody, I.; Otis, T. S.; Staley, K. J.; Kohr, G.; Macdonald, R. L.; Wasterlain, C. G.; Ticku, M. K.   THE BALANCE BETWEEN EXCITATION AND INHIBITION IN DENTATE GRANULE CELLS AND ITS ROLE IN EPILEPSY, Epilepsy Research, 1992; 331-339.
Mody, I.; Kohr, G.; Otis, T. S.; Staley, K. J.   THE ELECTROPHYSIOLOGY OF DENTATE GYRUS GRANULE CELLS IN WHOLE-CELL RECORDINGS, Epilepsy Research, 1992; 159-168.
Otis, T. S.; Staley, K. J.; Mody, I.   PERPETUAL INHIBITORY ACTIVITY IN MAMMALIAN BRAIN-SLICES GENERATED BY SPONTANEOUS GABA RELEASE, Brain Research, 1991; 545(1-2): 142-150.
Otis, T. S.; Gilly, W. F.   JET-PROPELLED ESCAPE IN THE SQUID LOLIGO-OPALESCENS - CONCERTED CONTROL BY GIANT AND NON-GIANT MOTOR AXON PATHWAYS, Proceedings of the National Academy of Sciences of the United States of America, 1990; 87(8): 2911-2915.