Thomas Otis

Thomas                         Otis                          Email: OTIST@UCLA.EDU
Phone: 310-206-0746
Address: 73-235 CHS
Research Interests: Cellular and molecular aspects of neural signaling

Research Interests:

Our brains accomplish (or sometimes fail at) their jobs by generating coordinated patterns of electrical signals in groups of nerve cells. Research in my laboratory focuses on the general question of how this coordination occurs. Circuits, single connections (synapses) and electrical properties particular to individual nerve cells combine to allow neurons to generate the specific firing patterns that ultimately result in thoughts, feelings and behaviors. My work concentrates on the cerebellar cortex, a region of the brain involved in coordinating movements and in refining them through practice. While a great deal is known about the firing patterns of particular types of cells in this part of the brain, we have a rudimentary understanding of how its circuitry generates these signals and modifies them during learning. The simple structure of the cerebellar cortex offers a remarkable context for studying these issues. It is made up of 6 types of neurons whose connectivity and ultrastructure are known in detail. There is one output and there are only two major inputs to the cerebellum. Surprisingly, most of this connectivity can be preserved in a 0.4 mm thick slice preparation of the cerebellum. In the reduced preparation, the output can be easily monitored, and each input can be reliably stimulated. Finally, well-defined patterns of stimulation can be used to recapitulate some of the circuit changes that occur during learning in an intact cerebellum. One set of projects in the lab explores a curious feature of the main output neurons of the cerebellum, the Purkinje neurons (PNs). PNs fire at high rates (~ 50 impulses / s) in the absence of any synaptic input - it is as if the output of the cerebellar cortex is "halfway on". We are interested in how synaptic inputs to such intrinsically active neurons influence their firing output. We are also examining how learning induced changes in synaptic inputs alter output. A second set of projects examines the process of neurotransmitter uptake at excitatory synaptic connections that use the neurotransmitter glutamate. Neurotransmitters transmit chemical signals between nerve cells. Such chemical signals cease only when neurotransmitter is actively taken back up into cells (hence the term "neurotransmitter uptake"). The process of neurotransmitter uptake is interesting to us because this mechanism is the target of action of very important classes of drugs including selective serotonin reuptake inhibitors (e.g. Prozac), amphetamines, and cocaine. Even so, we know very little about it. Unanswered questions include: How does neurotransmitter uptake influence the strength of synaptic signals' Does uptake help to determine which targets (i.e. types of neurotransmitter receptors) are signaled? Does the process of transmitter uptake change and are such changes involved in learning or disease? These and related questions are being addressed with a multidisciplinary approach combining electrophysiology, optical imaging of single neurons, and virus-mediated delivery of fluorescently-labeled signaling proteins.


Smith SL, Judy JW, Otis TS (2004). An ultra small array of electrodes for stimulating multiple inputs into a single neuron Journal of Neuroscience Methods 133: 109-14

Smith SL, Otis TS (2003). Persistent Changes in Spontaneous Firing of Purkinje Neurons Triggered by the Nitric Oxide Signaling Cascade The Journal of Neuroscience 23: 367-372

Otis TS, Brasnjo G, Dzubay JA, Pratap M (2003). Interactions between glutamate transporters and metabotropic glutamate receptors at excitatory synapses in the cerebellar cortex Neurochemistry International in press: -

Brasnjo G, Otis TS (2003). Glycine transporters not only take out the garbage, they recycle Neuron 40: 667-669

Smith SL, Otis TS (2002). No/cGMP pathway causes persistent changes in Purkinje neuron spontaneous activity Soc Neurosci Abstr 28: -

Brasnjo G, Otis TS (2002). Intracellular Tris+ substitution for physiological cations inhibits glutamate transporter currents recorded in Purkinje neurons Soc Neurosci Abstr 28: -

Otis TS (2002). Helping Thy Neighbors: Spillover at the Mossy Fiber Glomerulus Neuron 35: 412-414

Dzubay J, Otis TS (2002). Climbing Fiber Activation of Metabotropic Glutamate Receptors on Cerebellar Purkinje Neurons Neuron 36: 1159-1167

Dzubay JA, Otis TS (2002). An mGluR1 EPSC at climbing fiber synapses Soc Neurosci Abstr 28: -

Brasnjo G, Otis TS (2001). Control of mGluR signaling by postsynaptic glutamate transporters regulates LTD at parallel fiber synapses Soc Neurosci Abstr 27: -

Brasnjo G, Otis TS (2001). Neuronal glutamate transporters control activation of postsynaptic metabotropic glutamate receptors and influence long-term depression at cerebellar parallel fiber synapses Neuron 31: 607-616

Otis TS (2001). Vesicular glutamate transporters in cognito Neuron 29: 11-14

Otis TS, Kavanaugh MP (2000). Isolation of current components and partial reaction cycles in the glial glutamate transporter EAAT2 Journal of Neuroscience 20: 2749-2757

Brasnjo G, Otis TS (2000). Postsynaptic glutamate transporters limit signaling to mGluRs at parallel fiber synapses Soc Neurosci Abstr 26: -

Otis TS, Kavanaugh MP (1999). Kinetic analysis of EATT2 glutamate transporters Soc Neurosci Abstr 25: -

Otis TS, Kavanaugh MP (1999). Glutamate transporters and their contributions to excitatory synaptic transmission Handbook of Experimental Pharmacology 141: 419-40

Otis TS and Jahr CE (1998). Anion currents and predicted glutamate flux through a neuronal glutamate transporter Journal of Neuroscience 18: 7099- 7110

Trussell LO, Brenowitz S, Otis TS (1998). Postsynaptic mechanisms underlying synaptic depression Central Synapses: Quantal Mechanisms and Plasticity, Strasbourg, HFSP 149-58

Otis TS ,Kavanaugh MP and Jahr CE (1997). Postsynaptic glutamate transport at the climbing fiber-Purkinje neuron synapse Science 277: 1515-1518

Otis TS, Wu Y-C and Trussell LO (1996). Delayed clearance of transmitter and the role of glutamate transporters at a synapse with multiple release sites Journal of Neuroscience 16: 1634-1644

Trussell LO, Otis TS (1996). Physiology of AMPA receptors: biophysical characteristics that subserve integrative roles of synapses Excitatory Amino-acids and the Cerebral Cortex, Cambridge: MIT Press/Bradford Books 63-72

Otis TS, Zhang S, Trussell LO (1996). Direct measurement of AMPA receptor desensitization induced by glutamatergic synaptic transmission The Journal of Neuroscience 16: 7496-504

Otis TS, Trussell LO (1996). Inhibition of transmitter release shortens the duration of the excitatory synaptic current at a calyceal synapse Journal of Neurophysiology 76: 3584-8

Buhl EH, Otis TS, Mody I (1996). Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy model Science 271: 369-73

Otis TS, Raman IM, Trussell LO (1995). AMPA receptors with high CA(++) permeability mediate synaptic transmission in the auditory pathway of the chick Journal of Physiology 482.2: 309-15

Mody I, Otis TS, Bragin A, Hsu M, Buzsaki G (1995). GABAergic inhibitiion of granule cells and hilar neuronal synchrony following ischemia-induced hilar neuronal loss Neuroscience 69: 139-50

Otis TS, De Koninck Y, Mody I (1994). Lasting potentiation of inhibition is associated with an increased number of GABA(A) receptors activated during miniature IPSCs Proceedings of the National Academy of Sciences 91: 7698-702

Mody I, De Koninck Y, Otis TS, Soltesz I (1994). Bridging the cleft at GABA synapses in the brain Trends in Neurosciences V.17, N.12: 517-525

Otis TS, De Koninck Y, Mody I (1993). Characterization of synaptically elicited GABA(B) responses using patch-clamp recordings in rat hippocampal slices Journal of Physiology 463: 391-407

Otis TS, Mody I (1992). Modulation of decay kinetics and frequency of GABA(A) receptor-mediated spontaneous inhibitory postsynaptic currents in hippocampal neurons Neuroscience 49: 13-32

Otis TS, Mody I (1992). Differential activation of GABA(A) and GABA(B) receptors by spontaneous transmitter release Journal of Neurophysiology 67: 227-35

Otis TS, De Koninck Y, Mody I (1992). Whole-cell recordings of evoked and spontaneous GABA(B) responses in hippocampal slices Pharmacology Communications 2: 75-83

Staley KJ, Otis TS, Mody I (1992). Membrane properties of dentate gyrus granule cells: comparison of sharp microelectrode and whole-cell recordings Journal of Neurophysiology 67: 1346-58

Mody I, Otis TS, Staley KJ (1992). Action-potential independent spontaneous inhibitory activity in the mammalian brain Epilepsy and Inhibition, Urban & Schwarzenberg 1-14

Mody I, Otis TS, Staley KJ, Kohr GK (1992). The balance between excitation and inhibition in dentate granule cells and its role in epilepsy Molecular Neurobiology of Epilepsy, Elsevier 331-9

Mody I, Kohr GK, Otis TS, Staley KJ (1992). The electrophysiology of dentate gyrus granule cells in whole-cell recordings The Dentate Gyrus and Its Role in Seizures, Elsevier 159-68

Otis TS, Staley KJ, ModyI (1991). Perpetual inhibitory activity in mammalian brain slices generated by spontaneous GABA release Brain Research 545: 142-50

Otis TS, Gilly W (1990). Jet propelled escape in the squid Loligo opalescens: Concerted control by giant and non-giant motor axons Proceedings of the National Academy of Sciences 87: 2911-15