Anatomy and Neurobiology
Program In Neuroscience
Chair, Department Of Anatomy & Neurobiology; Director, Program In Neuroscience
Education and Training
- University of Missouri-Kansas City, BA, Philosophy, Mathematics and Psychology, 1967
- Massachusetts Institute of Technology, PhD, 1972
- Post-Doctorate, University of Oslo, Neurophysiology, 1973
- Post-Doctorate, University of Aarhus, Denmark, Neuroanatomy, 1974
A distinguished neuroscientist, Dr. Shipley is one of the world’s leading experts on the neural organization of the olfactory bulb—the part of the brain that processes information about odors. His research centers on understanding the organization, function, and development of neural networks using the mammalian olfactory bulb as a model cortical network.
Dr. Shipley has been continuously funded by the National Institutes of Health since 1982 and ranks above the 95th percentile in total funding over the past 30 years. Using advanced cell physiological and imaging methods, he and his research team at the University of Maryland School of Medicine have identified and defined the neuron types and their functional circuitry that comprise the glomerulus. The glomeruli are the neural circuits that encode raw odor sensory information into signals that engage higher brain networks to generate perception, motivation and behavior.
In 2010, Dr. Shipley and his team collaborated with scientists from Hungary and Japan using these state-of-the-art approaches to create 3D reconstructions of intra- and interglomerular connections. His current research focuses on the cellular and network bases of olfactory coding. Dr. Shipley has published over 185 peer-reviewed papers, invited reviews, and book chapters.
Neural Networks, Neurobiology of Olfactory Bulb Glomeruli, Glomerular Function, Glomerular Circuits
Liu S, Plachez C, Shao Z, Puche A, Shipley MT Olfactory bulb short axon cell release of GABA and dopamine produces a temporally biphasic inhibition-excitation response in external tufted cells. Journal of Neuroscience (2013) 33(7):2916-26.
Rothermel, M R Carey, A Puche, MT Shipley, and M Wachowiak Cholinergic inputs from basal forebrain add an excitatory bias to odor coding in the olfactory bulb. Journal of Neuroscience (2014) 34(14) 4654-64
Carey, RM, WE Sherwood, MT Shipley, A Borisyuk, M Wachowiak Role of intraglomerular circuits in shaping temporally structured responses to naturalistic inhalation-driven sensory input to the olfactory bulb. Journal of Neurophysiology 25 February 2015.
Liu, S, Z Shao, A Puche, M Wachowiak, M Rothermel, and MT Shipley Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt glomerular output Journal of Neuroscience 2015 Apr 8;35(14):
Brill, J, Z Shao, A Puche, M Wachowiak, MT Shipley Serotonin increases synaptic activity in olfactory bulb glomeruli Journal of Neurophysiology 2016 115:1208-1219
Brunert, D, Y Tsuno, M Rothermel, MT Shipley, M Wachowiak Cell type-specific modulation of sensory responses in olfactory bulb circuits by serotonergic projections from the raphe nuclei Journal of Neuroscience 2016 36:6820-6835.
Cockerham, R, S Liu, R Cachope, E Kiyokage, JF Cheer, MT Shipley, AC Puche Sub-second regulation of synaptically released dopamine by COMT in the olfactory bulb. Journal of Neuroscience 2016 36(29) 7779-7785.
Carlson, G., M.T. Shipley and A. Keller Long lasting depolarizations (LLDs) in olfactory bulb mitral cells. J. Neuroscience (2000)20 2011-2021.
Ennis, M. Zhou, F.M., L.A. Zimmer, Ciombor, K., Margolis, F., Aroniadou-Anderjaska, V., Shipley, M.T. Dopamine D2 Receptor-Mediated Presynaptic Inhibition of Olfactory Nerve Terminals. J. Neurophysiology (2001)86: 2986-2997.
Aungst, J.L., P.M. Heyward, A.C. Puche, S.V. Karnup, A. Hayar, G. Szabo, M.T. Shipley, Center-Surround Inhibition Among Olfactory Bulb Glomeruli. Nature (2003) 426:623-629.
Hayar, A., S. Karnup, M. T. Shipley, and M Ennis Olfactory Bulb Glomeruli: External Tufted Cells Intrinsically Burst at Theta Frequency and Are Entrained by Patterned Olfactory Input. Journal of Neuroscience (2004) 24 1190-1199.
Hayar, A., S. Karnup, M Ennis and M. T. Shipley, External Tufted Cells: A Major Excitatory Element that Coordinates Glomerular Activity. Journal of Neuroscience (2004) 24: 6676-6685.
Wachowiak M, McGann JP, Heyward PM, Shao Z, Puche AC, Shipley MT. Inhibition of olfactory receptor neuron input to olfactory bulb glomeruli mediated by suppression of presynaptic calcium influx. J. Neurophysiology (2005) 95: 2700-2712.
Hayar, A, MT Shipley and M Ennis Olfactory bulb external tufted cells are synchronized by multiple intraglomerular mechanisms Journal of Neuroscience (2005) 25: 8197-8208.
Wachowiak M, MT Shipley Coding and synaptic processing of sensory information in the glomerular layer of the olfactory bulb. Semin. Cell Dev Biol. (2006) 17:411-423.
Parrish-Aungst, S, MT Shipley, F Erdelyi, G Szabo, and AC Puche, Quantitative Analysis of Neuronal Diversity in the Mouse Olfactory Bulb. J. Comparative Neurology (2007) 501:825-836.
Liu S, MT Shipley Multiple conductances cooperatively regulate spontaneous bursting in mouse olfactory bulb external tufted cells. Journal of Neuroscience (2008) 28(7):1625-1639.
Liu, S and MT Shipley. Intrinsic Conductances Actively Shape Synaptic Responses In Mouse Olfactory Bulb External Tufted Cells. Journal of Neuroscience (2008) 28(41):10311-10322 (NIHMS72731).
Shao, Z., AC Puche, E Kiyokage, G Szabo and MT Shipley. Two GABAergic Circuits Differentially Regulate Tonic and Phasic Presynaptic inhibition of Olfactory Nerve Terminals. Journal of Neurophysiology (2009) 101(4):1988-2001.
Kiyokage E, Y Pan, Z Shao, K Kobayashi, G Szabo, Y Yanagawa, K. Obata, H. Okano, K. Toida, AC Puche and MT Shipley. Molecular Identity of Periglomerular and Short Axon Cells. Journal of Neuroscience (2010)30(3)1185-1196.
Parrish-Aungst, S., E. Kiyokag, G. Szabo, Y. Yanagawa, M. T. Shipley and A. C. Puche. Sensory experience selectively regulates transmitter synthetic enzymes in interglomerular circuits. Brain Res. (2011) 1382:70-6.
Liu, S JL Aungst, A Puche and MT. Shipley. Serotonin Modulates the Population Activity Profile of Olfactory Bulb External Tufted Cells. J. Neurophysiology (2012) 107:473-483.
All biological systems share common mechanisms at the cellular and molecular levels, yet they exhibit tremendous diversity of organization and function. This diversity arises at the level of cell-cell communication. The most complex degree of cell-cell communication is in the nervous system. In the brain, this complexity is expressed at the level of neural networks. Neural networks, thus, are the unique, defining characteristic of the nervous system. Our research centers on understanding the organization, function and development of neural networks using the mammalian olfactory bulb as a model cortical network.
From Molecules to Networks: The Neurobiology of Olfactory Bulb Glomeruli
Odorant molecules are transduced by olfactory receptor neurons (ORNs) in the nose. ORNs express a single odorant receptor (OR) from a total of ~1000 ORs. ORNs with the same OR project a few fixed glomeruli in the olfactory bulb. Glomeruli, thus, comprise a spatial map that reflects the moment-to-moment activity of ORNs. The brain ‘computes’ the identity, concentration and location of odors from these patterns of glomerular activity.
Patterns of glomerular input are transformed into output signals that are transmitted to olfactory cortex in the form of action potentials from mitral and tufted (MT) cells. Inhibitory circuits shape this transformation. We have identified four distinct glomerular inhibitory networks. Two of these are intraglomerular, operating at the level of a single glomerulus. Another, the interglomerular circuit, links hundreds of glomeruli in a network that uses lateral inhibition to normalize inputs to MT cells. A multiglomerular circuit links smaller numbers of neighboring glomeruli that are roughly the size of ‘clusters’ of glomeruli responsive to structurally similar or environmentally salient odors. Our central hypothesis is that OB inhibitory circuits are functionally organized to incorporate both spatial and temporal information to shape OB output. We are also testing the hypothesis that some of these inhibitory circuits are strongly modified by odor experience whereas others are not.
Olfaction is temporally dynamic. Odors are sampled by sniffing. This imposes a strong temporal structure on the patterns of input to olfactory glomeruli. Thus, in addition to spatial organization, the temporal structure of ON input to glomeruli contains information about odorant identity and concentration. Therefore, temporal sensory input patterns are likely to shape the postsynaptic processing of olfactory information. We have discovered that one type of glomerular neuron – the external tufted (ET) cell – links ON input to all these inhibitory circuits. ET cells intrinsically burst in the range of sniffing frequencies and are entrained by repetitive ON input. Thus, they are exquisitely well suited to endow glomerular inhibitory circuits with dynamic characteristics that can utilize information inherent in the temporal structure of olfactory input.
Our research aims to elucidate the neural machinery of olfactory bulb glomeruli. We use electrophysiological, optical imaging, optogenetics, computational, neuroanatomical, genetic, and molecular approaches to investigate the intrinsic characteristics of glomerular neurons, to elucidate the organization and dynamic properties of glomerular circuits, and to explore their contributions to the OB input-output function.
Central Modulation of Glomerular Function
Olfactory bulb output via mitral/tufted (MT) cells shows remarkable modulation of sensory responses in the awake animal. Glomerular circuits are targeted by centrifugal inputs from cortical and neuromodulatory centers in higher regions of the brain. As glomeruli are the first sites of synaptic integration in the sense of smell, modulation of these initial stages of odor coding impacts information processing at all subsequent levels of the brain. We are investigating how serotonin (5HT) and acetylcholine (ACh) from central neuromodulatory centers affects sensory processing in glomerular circuits. The research builds on recent advances in our understanding of these circuits and their importance in shaping OB output.
This research integrates information from bulb slices, anesthetized animals, and awake, head-fixed and freely moving mice. Our multidimensional research aims to link modulation of glomerular circuits to the activation of specific neuromodulatory systems – cholinergic inputs from the diagonal band and serotonergic inputs from the raphe nuclei. Our working hypothesis is that ACh and 5HT differentially modulate glomerular processing to shape both pre- and postsynaptic inhibition as well as MT cell excitability. We further hypothesize that ACh modulation reduces the impact of sensory input while at the same time increasing the excitability MT cells. This could reduce odor detection but increase discrimination. The research investigates modulation of early olfactory processing at levels ranging from cells and circuits in brain slices to single neurons and networks in anesthetized and head-fixed unanesthetized animals.
- Danish Medical Council Research Award, Oslo University, Institute of Physiology, 1973
- NIH Graduate Traineeship, Massachusetts Institute of Technology, Department of Psychology and Brain Sciences, 1968-1972
- Woodrow Wilson Fellowship, The Woodrow Wilson Foundation, Massachusetts Institute of Technology, 1967-1968
- Editorial Board, Chemical Senses, 1998-2005
- Editorial Board, Journal of Comparative Neurology, Associate Editor, Frontiers in Cellular Neuroscience, 2009-present
Brain slices: patch clamping recording, voltage sensitive dyes, Ca2+ imaging, gene-targeted GFP mice to record identified neurons, optogenetic activation of identified inputs, computational modeling of intrinsic cellular activity
Whole animal recording: anesthetized and awake freely-moving or head-fixed preparations, unit activity, optical imaging, optogenetics
Reconstructions of dye-filled, physiologically-characterized neurons; tract tracing, immunohistochemistry, image analysis
In situ hybridization, PCR, gene chips, proteomics, transgenic mice, optogenetics
- Dr. Adam Puche, Associate Professor: Neuroanatomy, electrophysiology, molecular biology
- Dr. Shaolin Liu, Assistant Professor: Slice and whole animal patch clamp recording
- Dr. Zouyi Shao, Assistant Professor: Slice patch clamp recording
- Dr. Ambarish Ghatpande, Research Associate: Slice electrophysiology
- Director, Center for Image Analysis, University of Cincinnati College of Medicine, 1985-1993
- Professor and Vice Chairman, Department of Anatomy & Cell Biology, University of Cincinnati College of Medicine, 1986-1993
Positions available for postdoctoral fellows (July 2010): We are seeking talented postdoctoral fellows to participate in a new project to investigate cholinergic and serotonergic modulation of olfactory bulb circuits and odor processing. The experiments involve interdisciplinary approaches ranging from single cell patch clamping/imaging in slices to unit recording recordings from anesthetized and awake, head-fixed mice. The project takes advantage of transgenic mice with GFP-labeling of specific neurons to target recordings to specific microcircuits, coupled with the use of optogenetic approaches to selectively activate cholinergic and serotonergic inputs in slices and whole animals. This is an opportunity to become involved in exciting research that is tightly coordinated between in vitro and in vivo experimental approaches. Contact Michael T. Shipley for more information.