The olfactory system is a model system for the study of many aspects of neuronal circuits and function. A central question that arises in many sensory systems, including the olfactory system is the extent to which patterns of spiking (as opposed to just the rate of spiking) are involved in the coding of sensory information. In recent years, considerable attention has been paid to this issue in the olfactory system. The work we describe in this proposal investigates cellular and circuit-level mechanisms that may make such temporal coding possible, focusing on the role of granule cell-mediated inhibition in regulating mitral cell firing. Despite years of work on mechanisms and function of spike time reliability and precision in many brain areas, little or no work has focused on the role of inhibition in generating accurate and reliable spike times. Clearly, temporal coding of spiking in excitatory neurons will require cooperation of interneurons and the nature of this cooperation is the focus of the experiments that we propose here. By imaging large populations of olfactory bulb granule cells in vitro we have shown that glomerular stimulation results in long latency, prolonged firing of granule cells, indicating that granule cell activity evolves over periods of seconds following a single stimulus. This long-lasting inhibition will be critical for the evolution of neuronal activity in the olfactory bulb. Understanding the mechanisms by which it is generated and regulated will be essential to understanding the transformations of odor-evoked activity in the bulb. Thus, we propose experiments to evaluate the hypothesis that long latency, granule cell mediated inhibition regulates the timing of mitral cell activity for hundreds of milliseconds following mitral cell activation.

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Despite years of work, scientists still do not understand the nature of the signals sent from one neuron to another and what aspects of neural activity are part of the signal, vs. part of the noise. Experiments in this proposal investigate some features of the temporal patterns of neuronal activity in the olfactory bulb and seek to determine the cellular and circuit level mechanisms that generate these firing patterns. Such studies are critical for understanding which aspects of neuronal activity are involved in signaling from one neuron to the next.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
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Somatosensory and Chemosensory Systems Study Section (SCS)
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Sullivan, Susan L
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Carnegie-Mellon University
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United States
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Burton, Shawn D; Urban, Nathaniel N (2014) Greater excitability and firing irregularity of tufted cells underlies distinct afferent-evoked activity of olfactory bulb mitral and tufted cells. J Physiol 592:2097-118
Tripathy, Shreejoy J; Savitskaya, Judith; Burton, Shawn D et al. (2014) NeuroElectro: a window to the world's neuron electrophysiology data. Front Neuroinform 8:40
Padmanabhan, Krishnan; Urban, Nathaniel N (2014) Disrupting information coding via block of 4-AP-sensitive potassium channels. J Neurophysiol 112:1054-66
Tripathy, Shreejoy J; Padmanabhan, Krishnan; Gerkin, Richard C et al. (2013) Intermediate intrinsic diversity enhances neural population coding. Proc Natl Acad Sci U S A 110:8248-53
Gerkin, Richard C; Tripathy, Shreejoy J; Urban, Nathaniel N (2013) Origins of correlated spiking in the mammalian olfactory bulb. Proc Natl Acad Sci U S A 110:17083-8
Padmanabhan, Krishnan; Urban, Nathaniel N (2010) Intrinsic biophysical diversity decorrelates neuronal firing while increasing information content. Nat Neurosci 13:1276-82
Hovis, Kenneth R; Padmanabhan, Krishnan; Urban, Nathaniel N (2010) A simple method of in vitro electroporation allows visualization, recording, and calcium imaging of local neuronal circuits. J Neurosci Methods 191:1-10
Urban, Nathaniel N; Castro, Jason B (2010) Functional polarity in neurons: what can we learn from studying an exception? Curr Opin Neurobiol 20:538-42
Castro, Jason B; Urban, Nathaniel N (2009) Subthreshold glutamate release from mitral cell dendrites. J Neurosci 29:7023-30
Ermentrout, G Bard; Galan, Roberto F; Urban, Nathaniel N (2008) Reliability, synchrony and noise. Trends Neurosci 31:428-34

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