Gordon Shepherd, MD, DPhil
Research & Publications
The main research interest of this laboratory is in the neuron as a complex system and in the synaptic organization of neurons into microcircuits in the brain. We focus on the ways that information processing by the neuron takes place through an interplay of the geometry of dendritic branching, the mechanisms of transduction of synaptic or sensory signals, and contributions of passive and active membrane properties.
Research Interests: Olfaction; synaptic organization; brain microcircuits; cortical evolution; computer modeling; neuroinformatics; history of neuroscience
Specialized Terms: Neuronal Dendrites; Dendritic Spines; Synaptic Organization; Olfactory System; Brain Microcircuits; Computational Neuroscience; Neuroinformatics; Functional Connectomes
Extensive Research Description
We use mammalian olfaction as a model system because it has several distinct advantages: the olfactory bulb (OB) receives direct sensory input from olfactory receptors, but is only one synapse from the cortical level of perception; the OB has distinct laminae and cell types which facilitates functional analysis; the OB projects to olfactory cortex (OC), with only a three-layered cortical organization rather than the six layers found in neocortex, which simplifies analysis of activity and connectivitypatterns; and the OB is located on the dorsal surface, which allows access for in vivo imaging and manipulations.
With these advantages we have identified key steps along the way to smell perception. Odor molecules first bind differentially to the olfactory receptors. Activity markers 2-deoxyglucose and fMRI show that the receptor responses are represented by activity patterns in the olfactory glomeruli.
These patterns are processed by feedback and lateral inhibition in microcircuits between mitral and granule cells. The resulting output goes to the three layer olfactory cortex, which we have postulated has a functional organization involving feedback inhibition and excitation. We postulate that this was elaborated in evolution to form six layer neocortex.
Our laboratory contains a computational unit, carrying forward early experiments with Wilfrid Rall, the founder of computational neuroscience and the theoretical foundations of dendritic function. We apply these principles in parallel with experiments to explore mechanisms of information processing in dendritic spines, dendritic trees and cortical microcircuits.
We were among the originators of neuroinformatics, developing the SenseLab Project for the construction of databases for ion currents, receptors, and neurotransmitters in different neuron types, to facilitate the integration of these multidisciplinary data into a new generation of scaled up realistic 3-dimensional computational models of neurons and neuronal systems. Among them is ModelDB, a widely-used curated archive of membrane, neuron and microcircuit models, to enhance the interplay of experiment and modeling for better insight into the cellular basis of brain function.
Anatomy; Dendrites; Information Science; Interneurons; Nervous System; Neurons; Synapses; Pyramidal Cells; Dendritic Spines; Organisms; Phenomena and Processes
- Twenty years of ModelDB and beyond: building essential modeling tools for the future of neuroscienceMcDougal RA, Morse TM, Carnevale T, Marenco L, Wang R, Migliore M, Miller PL, Shepherd GM, Hines ML. Twenty years of ModelDB and beyond: building essential modeling tools for the future of neuroscience Journal Of Computational Neuroscience 2016, 42: 1-10. PMID: 27629590, PMCID: PMC5279891, DOI: 10.1007/s10827-016-0623-7.
- Glomerular and Mitral-Granule Cell Microcircuits Coordinate Temporal and Spatial Information Processing in the Olfactory BulbCavarretta F, Marasco A, Hines ML, Shepherd GM, Migliore M. Glomerular and Mitral-Granule Cell Microcircuits Coordinate Temporal and Spatial Information Processing in the Olfactory Bulb Frontiers In Computational Neuroscience 2016, 10: 67. PMID: 27471461, PMCID: PMC4943958, DOI: 10.3389/fncom.2016.00067.
- Comparison of glomerular activity patterns by fMRI and wide-field calcium imaging: Implications for principles underlying odor mappingSanganahalli BG, Rebello MR, Herman P, Papademetris X, Shepherd GM, Verhagen JV, Hyder F. Comparison of glomerular activity patterns by fMRI and wide-field calcium imaging: Implications for principles underlying odor mapping NeuroImage 2015, 126: 208-218. PMID: 26631819, PMCID: PMC4733588, DOI: 10.1016/j.neuroimage.2015.11.048.
- Synaptic clusters function as odor operators in the olfactory bulbMigliore M, Cavarretta F, Marasco A, Tulumello E, Hines ML, Shepherd GM. Synaptic clusters function as odor operators in the olfactory bulb Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 8499-8504. PMID: 26100895, PMCID: PMC4500266, DOI: 10.1073/pnas.1502513112.
- Role of ortho‐retronasal olfaction in mammalian cortical evolutionRowe TB, Shepherd GM. Role of ortho‐retronasal olfaction in mammalian cortical evolution The Journal Of Comparative Neurology 2015, 524: 471-495. PMID: 25975561, PMCID: PMC4898483, DOI: 10.1002/cne.23802.
- Perception of Odors Linked to Precise Timing in the Olfactory SystemRebello MR, McTavish TS, Willhite DC, Short SM, Shepherd GM, Verhagen JV. Perception of Odors Linked to Precise Timing in the Olfactory System PLOS Biology 2014, 12: e1002021. PMID: 25514030, PMCID: PMC4267717, DOI: 10.1371/journal.pbio.1002021.
- Sparse Coding and Lateral Inhibition Arising from Balanced and Unbalanced Dendrodendritic Excitation and InhibitionYu Y, Migliore M, Hines ML, Shepherd GM. Sparse Coding and Lateral Inhibition Arising from Balanced and Unbalanced Dendrodendritic Excitation and Inhibition Journal Of Neuroscience 2014, 34: 13701-13713. PMID: 25297097, PMCID: PMC4188968, DOI: 10.1523/jneurosci.1834-14.2014.
- Distributed organization of a brain microcircuit analyzed by three-dimensional modeling: the olfactory bulbMigliore M, Cavarretta F, Hines ML, Shepherd GM. Distributed organization of a brain microcircuit analyzed by three-dimensional modeling: the olfactory bulb Frontiers In Computational Neuroscience 2014, 8: 50. PMID: 24808855, PMCID: PMC4010739, DOI: 10.3389/fncom.2014.00050.
- Symposium Overview and Historical PerspectiveShepherd GM. Symposium Overview and Historical Perspective Annals Of The New York Academy Of Sciences 2009, 1170: 215-223. PMID: 19686140, PMCID: PMC3819211, DOI: 10.1111/j.1749-6632.2009.03937.x.
- Odor-Evoked Oxygen Consumption by Action Potential and Synaptic Transmission in the Olfactory BulbLecoq J, Tiret P, Najac M, Shepherd GM, Greer CA, Charpak S. Odor-Evoked Oxygen Consumption by Action Potential and Synaptic Transmission in the Olfactory Bulb Journal Of Neuroscience 2009, 29: 1424-1433. PMID: 19193889, PMCID: PMC2662132, DOI: 10.1523/jneurosci.4817-08.2009.
- The NIF LinkOut Broker: A Web Resource to Facilitate Federated Data Integration using NCBI IdentifiersMarenco L, Ascoli GA, Martone ME, Shepherd GM, Miller PL. The NIF LinkOut Broker: A Web Resource to Facilitate Federated Data Integration using NCBI Identifiers Neuroinformatics 2008, 6: 219-227. PMID: 18975149, PMCID: PMC2704600, DOI: 10.1007/s12021-008-9025-y.
- Learning mechanism for column formation in the olfactory bulbMigliore M, Inzirillo C, Shepherd GM. Learning mechanism for column formation in the olfactory bulb Frontiers In Integrative Neuroscience 2007, 1: 12. PMID: 18958240, PMCID: PMC2526006, DOI: 10.3389/neuro.07.012.2007.
- An Energy Budget for the Olfactory GlomerulusNawroth JC, Greer CA, Chen WR, Laughlin SB, Shepherd GM. An Energy Budget for the Olfactory Glomerulus Journal Of Neuroscience 2007, 27: 9790-9800. PMID: 17804639, PMCID: PMC6672954, DOI: 10.1523/jneurosci.1415-07.2007.
- Viral tracing identifies distributed columnar organization in the olfactory bulbWillhite DC, Nguyen KT, Masurkar AV, Greer CA, Shepherd GM, Chen WR. Viral tracing identifies distributed columnar organization in the olfactory bulb Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 12592-12597. PMID: 16895993, PMCID: PMC1567923, DOI: 10.1073/pnas.0602032103.