Samantha J. Butler, Ph.D.

Academic Titles/Accomplishments/Affiliations: Member, Neuroscience GPB Home Area Associate Professor, Neurobiology Research interest: The extraordinarily diverse functions of the nervous system, from cognition to movement, are possible because neurons are assembled into precisely ordered networks that permit them to rapidly and accurately communicate with their synaptic targets. The Butler laboratory seeks to understand the mechanisms that establish these neuronal networks during development with the long-term goal of determining how this process may be co-opted to regenerate diseased or damaged circuits. Working the developing spinal cord, we have shown that molecules previously identified as morphogens, such as the Bone Morphogenetic Proteins (BMPs) family of growth factors, can also act as axon guidance signals. We are now determining the key intrinsic factors that translate the ability of the BMPs to direct cell fate and axon guidance decisions, two strikingly different processes in the generation of neural circuits. During the course of these studies, we have identified a critical mechanism by which the rate of axon outgrowth is controlled during embryogenesis, thereby permitting neural circuits to develop in synchrony with the rest of the embryo. The Butler laboratory is currently assessing how this mechanism can be harnessed to accelerate the regeneration of injured peripheral nerves. The successful implementation of this technology could result in significantly improved recovery times for patients with damaged nervous systems. Samantha received her B.A from Cambridge University, working in Michael Akam’s laboratory, where she was instilled with a love of developing systems. She joined Yash Hiromi’s lab, then at Princeton University, for her Ph.D. studying the genetic mechanisms that establish cell fate in the Drosophila eye.  Since neurons had become increasingly important to her as she lost them during her years as a graduate student, she joined Jane Dodd’s laboratory at Columbia University to examine axon guidance mechanisms in the developing vertebrate spinal cord. In her own laboratory as an Associate Professor at UCLA, Samantha explores how the developmental mechanisms that first establish neural circuits can be reused to ameliorate damaged or diseased nervous systems.  She is funded by the NIH, CIRM, Department of Defense, March of Dimes and the Craig H. Neilsen and Jean Perkins foundations Publications Gaber Zachary B, Butler Samantha J, Novitch Bennett G   PLZF Regulates Fibroblast Growth Factor Responsiveness and Maintenance of Neural Progenitors PLoS biology, 2013; 11(10): e1001676.

Kong J. H., Butler S. J., Novitch B. G.   My brain told me to do it Developmental cell, 2013; 25(5): 436-8.
Yamauchi K., Varadarajan S. G., Li J. E., Butler S. J.   Type Ib BMP receptors mediate the rate of commissural axon extension through inhibition of cofilin activity Development, 2013; 140(2): 333-42.
Hazen V. M., Andrews M. G., Umans L., Crenshaw E. B., Zwijsen A., Butler S. J.   BMP receptor-activated Smads confer diverse functions during the development of the dorsal spinal cordDevelopmental biology, 2012; 367(2): 216-27.
Hazen V. M., Phan K. D., Hudiburgh S., Butler S. J.   Inhibitory Smads differentially regulate cell fate specification and axon dynamics in the dorsal spinal cord Developmental biology, 2011; 356(2): 566-75.
Phan K. D., Croteau L.-P., Kam J. W. K., Kania A., Cloutier J.-F., Butler S. J.   Neogenin may functionally substitute for Dcc in chicken PloS one, 2011; 6(7): e22072.
Phan K. D., Hazen V. M., Frendo M.E., Jia Z.-P., Butler S.J.   The bone morphogenetic protein roof plate chemorepellent regulates the rate of commissural axonal growth Journal of Neuroscience, 2010; 30(46): 15430-40.
Hazen V. M., Phan K.D., Yamauchi K., Butler S. J.   Assaying the ability of diffusible signaling molecules to reorient embryonic spinal commissural axons JoVE, 2010; 31(37): .
Novitch B. G., Butler S. J.   Reducing the mystery of neuronal differentiation Cell, 2009; 138(6): 1062-4.
Yamauchi K., Phan K. D., Butler S. J.   BMP type I receptor complexes have distinct activities mediating cell fate and axon guidance decisions Development, 2008; 135(6): 1119-28.
Butler S. J., Tear G.   Getting axons onto the right path: the role of transcription factors in axon guidance Development, 2007; 134(3): 439-48.
Butler S. J., Dodd J.   A role for BMP heterodimers in roof plate-mediated repulsion of commissural axons Neuron, 2003; 38(3): 389-401.
Augsburger A., Schuchardt A., Hoskins S., Dodd J., Butler S.   BMPs as mediators of roof plate repulsion of commissural neurons Neuron, 1999; 24(1): 127-41.

Butler S. J., Ray S., Hiromi Y.   klingon, a novel member of the Drosophila immunoglobulin superfamily, is required for the development of the R7 photoreceptor neuron Development, 1997; 124(4): 781-92.

Dean Buonomano, Ph.D.

Academic Titles/Accomplishments/Affiliations:

Neurobiology
Member, Brain Research Institute
Molecular, Cellular & Integrative Physiology GPB Home Area
Neuroengineering Training Program
Neuroscience GPB Home Area

BIOGRAPHY

NEURAL DYNAMICS: THE NEURAL BASIS OF LEARNING AND MEMORY AND TEMPORAL PROCESSING Behavior and cognition are not the product of isolated neurons, but rather emerge from the dynamics of interconnected neurons embedded in complex recurrent networks. Significant progress has been made towards understanding cellular and synaptic properties in isolation, as well as in establishing which areas of the brain are active during specific tasks. However, elucidating how the activity of hundreds of thousands of neurons within local cortical circuits underlie computations remains an elusive and fundamental goal in neuroscience. The primary goal of my laboratory is to understand how functional computations emerge from networks of neurons. One computation we are particularly interested in is how the brain tells time. Temporal processing refers to your ability to distinguish the interval and duration of sensory stimuli, and is a fundamental component of speech and music perception. To answer these questions the main approaches in my laboratory involve: (1) In Vitro Electrophysiology: Using acute and chronic brain slices we study the spatio-temporal dynamics of cortical circuits, as well as the learning rules that allow networks to develop, organize and perform computations ??? that is, to learn. (2) Computer Simulations: Computer models are used to simulate how networks perform computations, as well as test and generate predictions in parallel with our experimental research. (3) Human Psychophysics: We also use human pyschophysical experiments to characterize learning and generalization of temporal tasks, such as interval discrimination.

PUBLICATIONS

Goudar Vishwa, Buonomano Dean V   A model of order-selectivity based on dynamic changes in the balance of excitation and inhibition produced by short-term synaptic plasticity Journal of neurophysiology, 2015; 113(2): 509-23.Goel Anubhuti, Buonomano Dean V   Timing as an intrinsic property of neural networks: evidence from in vivo and in vitro experiments Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2014; 369(1637): 20120460.Laje Rodrigo, Buonomano Dean V   Robust timing and motor patterns by taming chaos in recurrent neural networks Nature neuroscience, 2013; 16(7): 925-33.Lee Tyler P, Buonomano Dean V   Unsupervised formation of vocalization-sensitive neurons: a cortical model based on short-term and homeostatic plasticity Neural computation, 2012; 24(10): 2579-603.Buonomano Dean V, Laje Rodrigo   Population clocks: motor timing with neural dynamics Trends in cognitive sciences, 2010; 14(12): 520-7.Johnson Hope A, Goel Anubhuthi, Buonomano Dean V   Neural dynamics of in vitro cortical networks reflects experienced temporal patterns Nature neuroscience, 2010; 13(8): 917-9.Liu Jian K, Buonomano Dean V   Embedding multiple trajectories in simulated recurrent neural networks in a self-organizing manner The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009; 29(42): 13172-81.Buonomano Dean V   Harnessing chaos in recurrent neural networks Neuron, 2009; 63(4): 423-5.Buonomano Dean V, Bramen Jennifer, Khodadadifar Mahsa   Influence of the interstimulus interval on temporal processing and learning: testing the state-dependent network model Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2009; 364(1525): 1865-73.Carvalho Tiago P, Buonomano Dean V   Differential effects of excitatory and inhibitory plasticity on synaptically driven neuronal input-output functions Neuron, 2009; 61(5): 774-85.Buonomano Dean V, Maass Wolfgang   State-dependent computations: spatiotemporal processing in cortical networks Nature reviews. Neuroscience, 2009; 10(2): 113-25.Johnson Hope A, Buonomano Dean V   A method for chronic stimulation of cortical organotypic cultures using implanted electrodes Journal of neuroscience methods, 2009; 176(2): 136-43.van Wassenhove V, Buonomano DV, Shimojo S, Shams L.   Distortions of subjective time perception within and across senses, PLoS ONE, 2008; 3(1): e1437.Johnson, Hope A. Buonomano, Dean V.   Development and Plasticity of Spontaneous Activity and Up States in Cortical Organotypic Slices J. Neurosci, 2007; 27(22): 5915-5925.Buonomano, D. V.   The biology of time across different scales Nat Chem Biol, 2007; 3(10): 594-7.Karmarkar, U. R. Buonomano, D. V.   Timing in the absence of clocks: encoding time in neural network states Neuron, 2007; 53(3): 427-38.Karmarkar, U. R. Buonomano, D. V.   Different forms of homeostatic plasticity are engaged with distinct temporal profiles, Eur J Neurosci, 2006; 23(6): 1575-84.Eagleman, D. M. Tse, P. U. Buonomano, D. Janssen, P. Nobre, A. C. Holcombe, A. O.   Time and the brain: how subjective time relates to neural time, J Neurosci, 2005; 25(45): 10369-71.Dong, H. W. Buonomano, D. V.   A technique for repeated recordings in cortical organotypic slices, J Neurosci Methods, 2005; 146(1): 69-75.Buonomano, D. V.   A learning rule for the emergence of stable dynamics and timing in recurrent networks, J Neurophysiol, 2005; 94(4): 2275-83.Marder, C. P. Buonomano, D. V.   Timing and balance of inhibition enhance the effect of long-term potentiation on cell firing, J Neurosci, 2004; 24(40): 8873-84.Mauk, M. D. Buonomano, D. V.   The Neural Basis of Temporal Processing, Annual Rev. Neuroscience, 2004; 27: 304-340.Karmarkar, U. R. Buonomano, D. V.   Temporal specificity of perceptual learning in an auditory discrimination task, Learn Mem, 2003; 10(2): 141-7.Buonomano, D. V.   Timing of Neural Responses in Cortical Organotypic Slices, Proc. Natl. Acad. Sci. USA, 2003; 100: 4897-4902.Marder, C. P. Buonomano, D. V.   Differential effects of short- and long-term potentiation on cell firing in the CA1 region of the hippocampus, J Neurosci, 2003; 23(1): 112-21.Karmarkar, U. R. Buonomano, D. V.   A model of spike-timing dependent plasticity: one or two coincidence detectors?, J Neurophysiol, 2002; 88(1): 507-13.Buonomano, D. V. Karmarkar, U. R.   How do we tell time?, Neuroscientist, 2002; 8(1): 42-51.Karmarkar, U. R. Najarian, M. T. Buonomano, D. V.   Mechanisms and significance of spike-timing dependent plasticity, Biol Cybern, 2002; 87(5-6): 373-82.Buonomano, D. V.   Decoding temporal information: a model based on short-term synaptic plasticity, J Neurosci, 2000; 20: 1129-1141.Buonomano, D. V.   Distinct functional types of associative long-term potentiation in neocortical and hippocampal pyramidal neurons, J Neurosci, 1999; 19: 6748-6754.Buonomano, D. V. Merzenich, M.   A neural network model of temporal code generation and position-invariant pattern recognition, Neural Comput, 1999; 11(1): 103-16.Buonomano, D. V. Merzenich, M. M.   Cortical plasticity: from synapses to maps, Annual Rev. Neuroscience, 1998; 21: 149-186.Buonomano, D. V. Merzenich, M. M.   Temporal information transformed into a spatial code by a neural network with realistic properties, Science, 1995; 267: 1028-30.

Buonomano, D. V. Byrne, J. H.   Long-term synaptic changes produced by a cellular analog of classical conditioning in Aplysia, Science, 1990; 249(4967): 420-3.