The work in our lab focuses on understanding the physiological and circuit mechanisms underlying the functional and computational properties of brain neuronal networks, focusing on the olfactory system. In particular, we are interested in describing the detailed anatomical and physiological properties of cells and synapses, and then constructing models that provide insight into how these physiological properties give rise to the functional circuits that encode, transform and store information in the brain. Our goal is to use these models to understand the underlying computations that these physiological systems can be seen as implementing and to understand what happens when these mechanisms fail. I also see a goal of the lab as providing an environment in which students and postdocs can develop the technical and intellectual skills needed to become successful scientists.
Neuronal Diversity: Types and TeamsRecently, much interest has focused on questions about the number of different types of neurons in the brain, or in specific brain regions. Much of this work has focused on questions of molecular type. We are interested in questions about the functional differences between cell types at the level of intrinsic, synaptic, circuit and tuning properties. Using statistical models and techniques such as stimulus reconstruction we seek to determine how specific functions, such as stimulus encoding, are implemented by the different types of neurons in the networks performing these tasks. One element of this work has been focused on developing a public database of neuronal properties from the literature that we call NeuroElectro.org. Beyond differences across cell types, we have explored the functional consequences of cell-to-cell diversity. Within the population of cells of a given type we have shown that the cells display a range of properties and that this diversity can contribute to the ability of populations of cells to represent complex stimuli. We also have shown that in olfactory bulb mitral cells a significant fraction of this diversity is eliminated by blocking a single type of voltage-gated potassium channel. We are interested in the mechanisms that underlie this diversity and also in how differences in intrinsic properties relates to differences in synaptic connections.
Olfactory Navigation: Smelling your way
Animals have a remarkable ability to navigate using odor cues. Whether its scent dogs tracking a lost child or pocket rats finding landmines, the olfactory navigation many abilities of animals far outstrip any technological solutions developed by humans. As part of an multi-PI NSF-funded project we are trying to determine the algorithms and mechanisms used by animals to solve olfactory navigation problems. By coupling newly developed methods for analyzing the behavior of mice, flies and other species, with clever approaches to monitoring turbulent flow of odors, we will identify the cues used by animals performing these tasks and also understand how these cues are integrated by brain networks.
Neuronal Models: Stats + Math
Neuronal activity can be modeled in (at least) two ways - using statistical models and mechanistic models. Statistical models simply predict the spiking of a neuron given the input and the recent history of spiking. Mechanistic models incorporate what we know about channels and membranes to create models that not only capture the behavior, but also connect in clear ways to the biological features of neurons such as channel properties and densities. These two types of models offer important advantages: statistical models offer insight about what activity encodes or represents, whereas biophysical models allow predictions to be made about perturbations to biological features. We seek to connect statistical to biophysical models in order to answer questions like "What do Kv1.2 channels contribute to a neuron's ability to encode stimuli?"
Neuronal Reliability: What is Noise?
Neurons are unreliable. That is, neurons or populations of neurons that receive identical inputs many times over, do not respond identically time after time. Are biological devices just intrinsically unreliable? or are there advantages to this variability? What are the mechanisms of this variability and why is it enhanced in the brains of people with autism and also in mice with genetic mutations that mirror those seen in some patients with autism?
Olfactory Plasticity: Are you Experienced?
The relatively simple and highly stereotyped circuitry of early stages of the olfactory system make it an ideal system in which to analyze experience-dependent plasticity. We are analyzing how the connectivity and function of olfactory bulb circuits are influenced by changes to an animal's odor environment and determining whether these effects of experience are restricted to specific periods of development.
Urban Lab Publications
Urban Lab Publications on Pubmed
Chinestra P, Diabira D, Urban NN, Barrionuevo G, Ben-Ari Y. 1994. Major differences between long-term potentiation and ACPD-induced slow onset potentiation in hippocampus. Neurosci Lett 182:177-180.
Urban NN, Barrionuevo G. 1996. Induction of hebbian and non-hebbian mossy fiber long-term potentiation by distinct patterns of high-frequency stimulation. J Neurosci 16:4293-4299.
Urban NN, Henze DA, Lewis DA, Barrionuevo G. 1996. Properties of LTP induction in the CA3 region of the primate hippocampus. Learn Mem 3:86-95.
Urban NN, Barrionuevo G. 1998. Active summation of excitatory postsynaptic potentials in hippocampal CA3 pyramidal neurons. Proc Natl Acad Sci U S A 95: 11450-11455.
Berzhanskaya J, Urban NN, Barrionuevo G. 1998. Electrophysiological and pharmacological characterization of the direct perforant path input to hippocampal area CA3. J Neurophysiol 79: 2111-2118.
Urban NN, Henze DA, Barrionuevo G. 1998. Amplification of perforant-path EPSPs in CA3 pyramidal cells by LVA calcium and sodium channels. J. Neurophysiol. Volume: 80 Issue: 3 Pages: 1558-1561
Henze DA, Gonzalez-Burgos GR, Urban NN, Lewis DA, Barrionuevo G. Dopamine increases excitability of pyramidal neurons in primate prefrontal cortex. J Neurophysiol 2000 Dec; 84 (6 ):2799 -809 84: 2799-2809.
Henze DA, Urban NN, Barrionuevo G. 2000. The multifarious hippocampal mossy fiber pathway: a review. Neuroscience 2000 Jun 1; 98 (3):407 -427 98: 407-427.
Kanterewicz BI, Urban NN, McMahon DB, Norman ED, Giffen LJ, Favata MF, Scherle PA, Trzskos JM, Barrionuevo G, Klann E. 2000. The extracellular signal-regulated kinase cascade is required for NMDA receptor-independent LTP in area CA1 but not area CA3 of the hippocampus. J. Neuroscience 20 (9 ):3057-3066.
Thiels E, Urban NN, Gonzalez-Burgos GR, Kanterewicz BI, Barrionuevo G, Chu CT, Oury TD, Klann E. 2000. Impairment of long-term potentiation and associative memory in mice that overexpress extracellular superoxide dismutase. J. Neuroscience 20: 7631-7639.
Urban NN, Henze DA, Barrionuevo G. 2001. Revisiting the role of the hippocampal mossy fiber synapse. Hippocampus 11: 408-417.
Margrie TW, Sakmann B, Urban NN. 2001. Action potential propagation in mitral cell lateral dendrites is decremental and controls recurrent and lateral inhibition in the mammalian olfactory bulb. Proc Natl Acad Sci U S A 98: 319-324.
Urban NN, Sakmann B. 2002. Reciprocal intraglomerular excitation and intra- and interglomerular lateral inhibition between mouse olfactory bulb mitral cells. J Physiol 542: 355-367.
Urban NN, Gonzalez-Burgos G, Henze DA, Lewis DA, Barrionuevo G. 2002. Selective reduction by dopamine of excitatory synaptic inputs to pyramidal neurons in primate prefrontal cortex. J Physiol 539: 707-712.
Gonzalez-Burgos G, Kroner S, Krimer LS, Seamans JK, Urban NN, Henze DA, Lewis DA, Barrionuevo G. 2002. Dopamine modulation of neuronal function in the monkey prefrontal cortex. Physiol Behav 77: 537-543.
Urban NN. 2002. Lateral inhibition in the olfactory bulb and in olfaction. Physiol Behav 77: 607-612.
Schoppa NE, Urban NN. 2003. Dendritic processing within olfactory bulb circuits. Trends Neurosci 26: 501-506.
Gonzalez-Burgos G, Krimer LS, Urban NN, Barrionuevo G, Lewis DA. 2004. Synaptic efficacy during repetitive activation of excitatory inputs in primate dorsolateral prefrontal cortex. Cereb Cortex 14: 530-542.
Urban NN, Castro JB. 2005. Tuft calcium spikes in accessory olfactory bulb mitral cells. J. Neuroscience 25: 5024-5028.
Galan RF, Ermentrout GB, Urban NN. 2005. Efficient estimation of phase-resetting curves in real neurons and its significance for neural-network modeling. Phys Rev Lett 94: 158101.
Galán RF, Fourcaud-Trocme N, Ermentrout GB, Urban NN. 2006. Correlation-induced synchronization of oscillations in olfactory bulb neurons. J. Neuroscience, 26(14):3646-55.
Egger V, Urban NN. 2006. Dynamic lateral inhibition in the mitral cell-granule cell microcircuit. Seminars in Cell and Developmental Biology, 17: 424-432.
Galán RF, Ermentrout GB, Urban NN. 2006. Reliability, discriminability and noise-induced synchronization of olfactory neurons. Sensors and Actuators B: Chemical, 116, p. 168-173.
Galán RF, Ermentrout GB, Urban NN. 2007. Reliability and stochastic synchronization in type I vs. type II neural oscillators. Neurocomputing, 70:2102-2106.
Kapoor V and Urban NN. 2006. Glomerulus-specific, long latency activity in the olfactory bulb granule-cell network. J. Neuroscience. 2006 Nov 8;26(45):11709-19.
Castro JB, Hovis KR, Urban NN. 2007. Recurrent dendrodendritic inhibition of accessory olfactory bulb mitral cells requires activation of group I metabotropic glutamate receptors. J. Neuroscience 27(21):5664-71.
Bagley J, LaRocca G, Jimenez DA, Urban NN. 2007. Adult neurogenesis and specific replacement of interneuron subtypes in the mouse main olfactory bulb. BMC Neuroscience. 8(1):92.
Galán RF, Ermentrout GB, Urban NN. 2007. Stochastic dynamics of uncoupled neural oscillators: Fokker Planck studies with the finite element method. Physical Review E. 76(5 Pt 2):056110.
Ermentrout GB, Galán RF, Urban NN. 2007. Relating neural dynamics to neural coding. Physical Review Letters. 99. 248103. Faculty of 1000 Must Read.
Galán RF, Ermentrout GB, Urban NN. 2008. Optimal time scale for spike-time reliability: Theory, simulations and experiments. J Neurophysiol. 99(1):277-83.
Arevian AC, Kapoor V, Urban NN. 2008. Activity-dependent gating of lateral inhibition in the mouse olfactory bulb. Nature Neuroscience. 11(1):80-7.
Ermentrout GB, Galán RF, Urban NN. 2008. Reliability, synchrony and noise. Trends Neurosci. Aug;31(8):428-34.
Castro JB, Urban NN. 2009. Subthreshold glutamate release from mitral cell dendrites. J. Neuroscience. May 27; 29(21):7023-30.
Castro JB, Urban NN. 2010. Functional polarity in neurons: what can we learn from studying an exception? Current Opinion in Neurobiology. Oct; 20(5):538-42.
Hovis KR, Padmanabhan K, Urban NN. 2010. A Simple Method of In Vitro Electroporation Allows Visualization, Recording, and Calcium Imaging of Local Neuronal Circuits. J. Neuroscience Methods. Aug 15; 191(1):1-10.
Padmanabhan K and Urban NN. 2010. Intrinsic biophysical diversity decorrelates neuronal firing while increasing information content. Nature Neuroscience. 2010 Oct; 13(10):1276-82.
Giridhar S, Doiron B, Urban NN. 2011. Timescale-dependent shaping of correlation by olfactory bulb lateral inhibition. Proc Natl Acad Sci U S A. 2011 Apr 5; 108(14):5843-8. Epub 2011 Mar 21.
Dahlen JE, Jimenez DA, Gerkin RC, Urban NN. 2011. Morphological analysis of activity-reduced adult-born neurons in the mouse olfactory bulb. Front Neurosci. 2011; 5:66.
Litwin-Kumar A, Oswald, AM, Urban NN and Doiron B. 2011. Balanced synaptic input shapes the correlation between neural spike trains. PloS Computational Biology. 2011 Dec;7(12):e1002305.
Oswald AM, Urban NN. 2012. Interactions between behaviorally relevant rhythms and synaptic plasticity alter coding in the piriform cortex. J Neurosci. May 2; 32(18):6092-104.
Hovis KR, Ramnath R, Dahlen JE, Romanova AL, LaRocca G, Bier ME, Urban NN. 2012. Activity Regulates Functional Connectivity from the Vomeronasal Organ to the Accessory Olfactory Bulb. J. Neurosci. Jun 6;32(23):7907-16.
Giridhar S, Urban NN. 2012. Mechanisms and benefits of granule cell latency coding in the mouse olfactory bulb. Frontiers in Neural Circuits 2012; 6:40.
Burton SD, Ermentrout GB, Urban NN. 2012. Intrinsic heterogeneity in oscillatory dynamics limits correlation-induced neural synchronization. In revision. J. Neurophysiol. 2012 Jul 18. [Epub ahead of print] PMID: 22815400.
Urban NN, Tripathy, S. 2012. Circuits Drive Cell Diversity. Nature. 2012 Aug 16; 488(7411):289-90. doi: 10.1038/488289a
Tripathy SJ, Padmanabhan K, Gerkin RC, Urban NN. 2013. Intermediate intrinsic diversity enhances neural population coding. Proc Natl Acad Sci USA 110:8248-8253.
Gerkin RC, Tripathy SJ, Urban NN. 2013. Origins of correlated spiking in the mammalian olfactory bulb. Proc Natl Acad Sci USA. 2013 Oct 15;110(42):17083-8. doi: 10.1073/pnas.1303830110. Epub 2013 Sep 30.
De Waard A, Burton SD, Gerkin RC, Harviston M, Marques D, Tripathy SJ, Urban NN. 2013. A System for Electrophysiology Data Management and Exploration. AAAI 2013 Fall Symposium on Discovery Informatics.
Zhou P, Burton SD, Urban NN, Ermentrout GB. 2013. Impact of neuronal heterogeneity on correlated colored noise-induced synchronization. Aug 21;7:113. doi: 10.3389/Front Comput Neurosci. ncom.2013.00113.
Oswald AM, Urban NN. 2012. There and back again: the corticobulbar loop. Neuron. 2012 Dec 20;76(6):1045-7. doi: 10.1016/j.neuron.2012.12.006. PMID:23259940
Burton, S.D., Urban, N.N. 2014. Greater excitability and firing irregularity of tufted cells underlies distinct afferent-evoked activity of olfactory bulb mitral and tufted cells. J Physiol. 2014 Mar 10.
Padmanabhan K, Urban NN. 2014. Disrupting information coding via block of 4-AP-sensitive potassium channels. J Neurophysiol. Sep 1;112(5):1054-66.
Tripathy SJ, Savitskaya J, Burton SD, Urban NN, Gerkin RC. 2014. NeuroElectro: a window to the world's neuron electrophysiology data. Front Neuroinform. 2014 Apr 29;8:40. doi: 10.3389/fninf.2014.00040.
Tripathy SJ, Burton SD, Geramita M, Gerkin RC, Urban NN. 2015. Brain-wide analysis of electrophysiological diversity yields novel categorization of mammalian neuron types. J Neurophysiol. 2015 Mar 25:jn.00237.2015. doi: 10.1152/jn.00237.2015.
Wang W, Tripathy SJ, Padmanabhan K, Urban NN, Kass RE. 2015. An Empirical Model for Reliable Spiking Activity. Neural Comput. 2015 Aug;27(8):1609-23. doi: 10.1162/NECO_a_00754. Epub 2015 Jun 16.
Yu Y, Burton, SD, Tripathy SJ, Urban NN, 2015. Postnatal development attunes olfactory bulb mitral cells to high frequency signaling. J Neurophysiology.2015 Nov;114(5):2830-42. doi: 10.1152/jn.00315.2015. Epub 2015 Sep 9. PMID: 26354312
Zhou PC, Burton SD, Snyder AC, Smith MA, Urban NN and Kass RE. 2015. Establishing a Statistical Link Between Network Oscillations and Neural Synchrony. PLoS Computational Biology. 2015 Oct 14;11(10):e1004549. doi: 10.1371/journal.pcbi.1004549. eCollection 2015 Oct. PMID: 26465621
Burton SD, Urban NN. 2015. Rapid Feedforward Inhibition and Asynchronous Excitation Regulate Granule Cell Activity in the Mammalian Main Olfactory Bulb. J Neurosci. 2015 Oct 21;35(42):14103-22. doi: 10.1523/JNEUROSCI.0746-15.2015. PMID: 26490853
Geramita MA, Burton SD, Urban NN. 2016. Distinct lateral inhibitory circuits drive parallel processing of sensory information in the mammalian olfactory bulb. Elife. 2016 Jun 28;5. pii: e16039. doi: 10.7554/eLife.16039. PMID: 27351103.
Liu, A Savya S and Urban N. 2016. Early Odorant Exposure Increases the Number of Mitral and Tufted Cells Associated with a Single Glomerulus.J Neurosci. 2016 Nov 16;36(46):11646-11653. PMID:27852773
Geramita M, Urban NN. 2016. Differences in glomerular layer- mediated feed-forward inhibition onto mitral and tufted cells lead to distinct modes of intensity coding. J Neurosci. 2016 Dec 27. pii: 2245-16. doi: 10.1523/JNEUROSCI.2245-16.2016. PMID: 28028200
Geramita M, Urban NN. 2016. Postnatal Odor Exposure Increases the Strength of Interglomerular Lateral Inhibition onto Olfactory Bulb Tufted Cells. J Neurosci. 2016 Dec 7;36(49):12321-12327.PMID: 27927952
Burton SD, LaRocca G, Liu A, Cheetham CE, Urban NN. 2016. Olfactory bulb deep short-axon cells mediate widespread inhibition of tufted cell apical dendrites. J Neurosci. 2016 Dec 21. pii: 2880-16. doi: 10.1523/JNEUROSCI.2880-16.2016. PMID:28003347.
Geramita M, Urban NN. Differences in Glomerular-Layer-Mediated Feedforward Inhibition onto Mitral and Tufted Cells Lead to Distinct Modes of Intensity Coding. J Neurosci. 2017 Feb 8;37(6):1428-1438. doi: 10.1523/JNEUROSCI.2245-16.2016. Epub 2016 Dec 27. PMID:28028200
Case DT, Burton SD, Gedeon JY, Williams SG, Urban NN, Seal RP. Layer- and cell type-selective co-transmission by a basal forebrain cholinergic projection to the olfactory bulb. Nat Commun. 2017 Sep 21;8(1):652. doi: 10.1038/s41467-017-00765-4. PMID: 28935940.
Liu, A and Urban NN. Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb. eNeuro 25 September 2017, ENEURO.0129-17.2017; DOI: https://doi.org/10.1523/ENEURO.0129-17.2017.