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.
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.
Member, Brain Research Institute
Molecular, Cellular & Integrative Physiology GPB Home Area
Neuroengineering Training Program
Neuroscience GPB Home Area
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.
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.
Neurochemical and Anatomical Pathways in the Vertebrate Retina that Mediate Vision Dr. Brecha’s major research interest is concerned with understanding the functional organization of the mammalian retina by elucidating its morphology and neurochemistry. Specific investigations are focused on defining the microcircuitry of the inner retina, evaluating the neurochemical organization and regulation of both its fast (amino acid) and slow (peptide) transmitter systems, and the function of bipolar, amacrine and ganglion cell populations, which are major retinal cell types that play critical roles in the processing of visual information. Recent investigations concerned with peptide-containing cell populations are defining the cellular expression patterns of tachykinin, somatostatin, neuropeptide Y and opiate receptors, and their functional role in modulating bipolar cell responsiveness. Morphological studies have shown that peptide receptor subtypes are selectively expressed by different populations of bipolar, amacrine and ganglion cells. These observations have provided important clues to the organization of the retinal microcircuits mediating different aspects of vision, as well as the sites of action of several previously identified retinal transmitter substances. A new research direction, developed over the past three years has been focused on determining the function of peptides in the retina. The rationale of these studies is to define the cellular actions of peptides found in the retina, which we hypothesize modulate cellular responsiveness, to influence ion channels and other intercellular messenger systems. Initial studies have focused on somatostatin; our findings demonstrate that this peptide inhibits both K+ and Ca2+ ion channels in the axonal terminals of bipolar cells and photoreceptors at low concentrations. Interestingly, these cells prominently express the somatostatin receptor subtype, sst2A suggesting this action is mediated through this receptor. These investigations provide further support for a role of somatostatin in the presynaptic modulation of transmitter release from retinal cells.
Liu Xue, Hirano Arlene A, Sun Xiaoping, Brecha Nicholas C, Barnes Steven Calcium channels in rat horizontal cells regulate feedback inhibition of photoreceptors through an unconventional GABA- and pH-sensitive mechanism The Journal of physiology, 2013; .
Zampighi GA, Schietroma C, Zampighi LM, Woodruff M, Wright EM, Brecha NC Conical tomography of a ribbon synapse: structural evidence for vesicle fusion PLoS One, 2011; 6(3): e16944.
Zampighi Guido A, Schietroma Cataldo, Zampighi Lorenzo M, Woodruff Michael, Wright Ernest M, Brecha Nicholas C Conical tomography of a ribbon synapse: structural evidence for vesicle fusion PloS one, 2011; 6(3): e16944.
Hirano AA, Brandstätter JH, Morgans CW, Brecha NC SNAP25 expression in mammalian retinal horizontal cells J Comp Neurol, 2011; 519(5): 972-88.
Hirano Arlene A, BrandstÃ¤tter Johann Helmut, Morgans Catherine W, Brecha Nicholas C SNAP25 expression in mammalian retinal horizontal cells The Journal of comparative neurology, 2011; 519(5): 972-88.
Guo C, Hirano AA, Stella SL Jr, Bitzer M, Brecha NC Guinea pig horizontal cells express GABA, the GABA-synthesizing enzyme GAD 65, and the GABA vesicular transporter J Comp Neurol, 2010; 518(10): 1674-69.
Guo Chenying, Hirano Arlene A, Stella Salvatore L, Bitzer Michaela, Brecha Nicholas C Guinea pig horizontal cells express GABA, the GABA-synthesizing enzyme GAD 65, and the GABA vesicular transporter The Journal of comparative neurology, 2010; 518(10): 1647-69.
Lee H, Brecha NC Immunocytochemical evidence for SNARE protein-dependent transmitter release from guinea pig horizontal cells Eur J Neurosci, 2010; 31(8): 1388-401.
Lee Helen, Brecha Nicholas C Immunocytochemical evidence for SNARE protein-dependent transmitter release from guinea pig horizontal cells The European journal of neuroscience, 2010; 31(8): 1388-401.
Farrell SR, Raymond ID, Foote M, Brecha NC, Barnes S Modulation of voltage-gated ion channels in rat retinal ganglion cells mediated by somatostatin receptor subtype 4 J Neurophysiol, 2010; 104(3): 1347-54.
Raymond ID, Pool AL, Vila A, Brecha NC A Thy1-CFP DBA/2J mouse line with cyan fluorescent protein expression in retinal ganglion cells Vis Neurosci. 2009 Nov;26(5-6):453-65, 2009; 26(5-6): 453-65.
Raymond Iona D, Pool Angela L, Vila Alejandro, Brecha Nicholas C A Thy1-CFP DBA/2J mouse line with cyan fluorescent protein expression in retinal ganglion cells Visual neuroscience, 2009; 26(5-6): 453-65.
Stella SL Jr, Hu WD, Brecha NC Adenosine suppresses exocytosis from cone terminals of the salamander retina Neuroreport, 2009; 20(10): 923-9.
Stella Salvatore L, Hu Wanda D, Brecha Nicholas C Adenosine suppresses exocytosis from cone terminals of the salamander retina Neuroreport, 2009; 20(10): 923-9.
Guo Chenying, Stella Salvatore L, Hirano Arlene A, Brecha Nicholas C Plasmalemmal and vesicular gamma-aminobutyric acid transporter expression in the developing mouse retina The Journal of comparative neurology, 2009; 512(1): 6-26.
Stella Salvatore L, Li Stefanie, Sabatini Andrea, Vila Alejandro, Brecha Nicholas C Comparison of the ontogeny of the vesicular glutamate transporter 3 (VGLUT3) with VGLUT1 and VGLUT2 in the rat retina Brain research, 2008; 1215(1): 20-9.
Raymond Iona D, Vila Alejandro, Huynh Uyen-Chi N, Brecha Nicholas C Cyan fluorescent protein expression in ganglion and amacrine cells in a thy1-CFP transgenic mouse retina Molecular vision, 2008; 14(1): 1559-74.
Anselmi Nicholas C, Stella Nicholas C, Brecha Nicholas C, Sternini Nicholas C Galanin inhibition of voltage-dependent Ca(2+) influx in rat cultured myenteric neurons is mediated by galanin receptor 1 Journal of neuroscience research, 2008; 512(1): 1107-14.
Hirano Arlene A, Brandstätter Johann Helmut, Vila Alejandro, Brecha Nicholas C Robust syntaxin-4 immunoreactivity in mammalian horizontal cell processes Visual neuroscience, 2008; 24(4): 489-502.
Stella Salvatore L, Hu Wanda D, Vila Alejandro, Brecha Nicholas C Adenosine inhibits voltage-dependent Ca2+ influx in cone photoreceptor terminals of the tiger salamander retina Journal of neuroscience research, 2007; 85(5): 1126-37.
Wang Yuan, Luksch Harald, Brecha Nicholas C, Karten Harvey J Columnar projections from the cholinergic nucleus isthmi to the optic tectum in chicks (Gallus gallus): a possible substrate for synchronizing tectal channels The Journal of comparative neurology, 2006; 494(1): 7-35.
Casini Giovanni, Rickman Dennis W, Brecha Nicholas C Expression of the gamma-aminobutyric acid (GABA) plasma membrane transporter-1 in monkey and human retina Investigative ophthalmology & visual science, 2006; 47(4): 1682-90.
Chang Bo, Heckenlively John R, Bayley Philippa R, Brecha Nicholas C, Davisson Muriel T, Hawes Norm L, Hirano Arlene A, Hurd Ronald E, Ikeda Akihiro, Johnson Britt A, McCall Maureen A, Morgans Catherine W, Nusinowitz Steve, Peachey Neal S, Rice Dennis S, Vessey Kirstan A, Gregg Ronald G The nob2 mouse, a null mutation in Cacna1f: anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses Visual neuroscience, 2006; 23(1): 11-24.
Hirano Arlene A, Brandstätter Johann H, Brecha Nicholas C Cellular distribution and subcellular localization of molecular components of vesicular transmitter release in horizontal cells of rabbit retina The Journal of comparative neurology, 2005; 488(1): 70-81.
D’Angelo I, Brecha NC. Y2 receptor expression and inhibition of voltage-dependent Ca2+ influx into rod bipolar cell terminals, Neuroscience, 2004; 125(4): 1039-49.
Minnis JG, Patierno S, Kohlmeier SE, Brecha NC, Tonini M, Sternini C. Ligand-induced mu opioid receptor and endocytosis and recycling in enteric neurons, Neuroscience, 2003; 119(1): 33-42.
Oh Su-Ja, D’Angelo Iona, Lee Eun-Jin, Chun Myung-Hoon, Brecha Nicholas C Distribution and synaptic connectivity of neuropeptide Y-immunoreactive amacrine cells in the rat retina The Journal of comparative neurology, 2002; 446(3): 219-34.
Casini, G Sabatini, A Catalani, E Willems, D Bosco, L Brecha, NC Expression of the neurokinin 1 receptor in the rabbit retina Neuroscience. , 2002; 115(4): 1309-21.
D’Angelo Iona, Oh Su-Ja, Chun Myung-Hoon, Brecha Nicholas C Localization of neuropeptide Y1 receptor immunoreactivity in the rat retina and the synaptic connectivity of Y1 immunoreactive cells The Journal of comparative neurology, 2002; 454(4): 373-82.
Cueva Juan G, Haverkamp Silke, Reimer Richard J, Edwards Robert, Wässle Heinz, Brecha Nicholas C Vesicular gamma-aminobutyric acid transporter expression in amacrine and horizontal cells The Journal of comparative neurology, 2002; 445(3): 227-37.
Kang, WS Lim, MY Lee, EJ Kim, IB Oh, SJ Brecha, NC Park, CB Chun, MH Light- and electron-microscopic analysis of neuropeptide Y-immunoreactive amacrine cells in the guinea pig retina Cell and tissue research. , 2001; 306(3): 363-71.
Casini, G Brecha, NC Bosco, L Rickman, DW Developmental expression of neurokinin-1 and neurokinin-3 receptors in the rat retina The Journal of comparative neurology. , 2000; 421(2): 275-87.
Melone, M Brecha, NC Sternini, C Evans, C Conti, F Etorphine increases the number of mu-opioid receptor-positive cells in the cerebral cortex Neuroscience. , 2000; 100(3): 439-43.
Sternini, C Brecha, NC Minnis, J D’Agostino, G Balestra, B Fiori, E Tonini, M Role of agonist-dependent receptor internalization in the regulation of mu opioid receptors Neuroscience. , 2000; 98(2): 233-41.
Akopian, A., Johnson, J., Gabriel, R., Brecha, N.C. and P. Witkovsky Somatostatin modulates voltage-gated K+ and Ca2+ currents in rod and cone photoreceptors of the salamander retina, Journal of Neuroscience 20:929-936, 2000; 20: 929-936.
Johnson, J Wu, V Wong, H Walsh, JH Brecha, NC Somatostatin receptor subtype 2A expression in the rat retina Neuroscience. , 1999; 94(3): 675-83.
Johnson, J Wong, H Walsh, JH Brecha, NC Expression of the somatostatin subtype 2A receptor in the rabbit retina The Journal of comparative neurology. , 1998; 393(1): 93-101.
Casini, G Rickman, DW Sternini, C Brecha, NC Neurokinin 1 receptor expression in the rat retina The Journal of comparative neurology. , 1997; 389(3): 496-507.
Johnson, J., Chen, T.K., Rickman, D.W., Evans, C., and Brecha, N.C Multiple g-aminobutyric acid plasma membrane transporters (GAT-1, GAT-2 and GAT-3) in the rat retina, Journal of Comparative Neurology, 1996; 375: 212-224.
Rickman, DW Blanks, JC Brecha, NC Somatostatin-immunoreactive neurons in the adult rabbit retina The Journal of comparative neurology. , 1996; 365(3): 491-503.
Brecha, N., Johnson, J., Kui, R., Anton, B., Keith Jr., D., Evans, C., and Sternini, C. Mu opioid receptor immunoreactivity is expressed in the retina and retinal-recipient nuclei, Analgesia, 1995; 1: 331-334.
Corey, JL Davidson, N Lester, HA Brecha, N Quick, MW Protein kinase C modulates the activity of a cloned gamma-aminobutyric acid transporter expressed in Xenopus oocytes via regulated subcellular redistribution of the transporter The Journal of biological chemistry. , 1994; 269(20): 14759-67.