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Project List


Full Shepherd bibliography with chapters, reviews and books available here.

Brain Microcircuits

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We carry out research on nerve cells as complex integrative systems. The current experimental approaches with our colleagues include in vitro and in vivo electrophysiology, optogenetics, and high-resolution functional brain imaging. This and other work on microcircuits throughout the brain is collected in Handbook of Brain Microcircuits, edited by GM Shepherd and S Grillner.

Handbook of Brain Microcircuits.

Computational Modeling

Our lab has pioneered applying realistic computational modeling methods to experimental data, to reveal mechanisms of information processing in dendritic spines, dendritic trees, and cortical microcircuits.  Our methods include 3D models and the first 3D printer neurons.
Video: Computational Modeling

Video: Computational Modeling

Computational Modeling Video

Cortical evolution

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The earliest mammalian brains were dominated by olfactory cortex.  We are developing evidence that the basic functional principles are embedded in neocortex.

Rowe TB, Shepherd GM: Role of ortho-retronasal olfaction in mammalian cortical evolution. J Comp Neurol. 2016 Feb 15; 2015 Jun 11. PMID: 25975561.

Shepherd, Gordon. (2011). "The microcircuit concept applied to cortical evolution: from three-layer to six-layer cortex"


The Olfactory System

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Main Connections of the Olfactory System

Odorant molecules bind to receptors on olfactory sensory neurons (OSNs) in the olfactory epithelium (OE), initiating an action potential. OSN populations that express a single receptor type (the segregated information represented as magenta, dark green, or orange cell somas) converge onto glomeruli (GL) in the olfactory bulb (OB). Periglomerular (PG) cells act in a mainly inhibitory manner at the glomerular level. Tufted cells (TC) and mitral cells (MC) innervate single glomeruli and project information to the pyramidal cells (PC) in the olfactory cortex. Granule cells (GC) inhibit MCs and TCs at synapses on their lateral dendrites and cell somas. PCs send centrifugal fibers to the GCs. Small arrows indicate the direction of postsynaptic potential and action potential propagation.

Neurogastronomy

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Recognition of odor images, and the importance of retronasal smell, are giving us a new understanding of how the brain creates the perception of food flavor.  This is contributing to the current intense interest in brain mechanisms underlying healthy eating and disorders such as obesity.

How the Brain Creates Flavor and Why It Matters.


Neuroenology (Neuro-oenology)

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The neurogastronomical approach is also giving rise to a new scientific understanding of how the brain creates the taste of wine.

How the Brain Creates the Flavor of Wine

Neuroenology: How the Brain Creates the Taste of Wine.



Neuroinformatics

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Through our integrative approach our lab is pioneering in the development of neuroinformatics.  The SenseLab Project contains 9 databases to facilitate the integration of multidisciplinary data, including over 14,000 olfactory receptor-like genes and 900 computational models.  We are building tools to organize and navigate functional connectomes.   CellPropDB, NeuronDB, ModelDB, MicrocircuitDB, 3DModelDB, ORDB, OdorDB, OdorMapDB, ORModelDB, BrainPharm

The SenseLab Project

Neuroscience History

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We stand on the shoulders of giants.  This perspective has been explored in studies of the founding of the neuron doctrine, the rise of modern neuroscience in the 1950s, the origins of brain imaging and cognitive neuroscience, and a biography in preparation of John Farquhar Fulton.

Creating Modern Neuroscience: The Revolutionary 1950s.

Cajal's Breakthrough, 1889

Background

I heard about the video from Juan Lermo on a visit to the Cajal Institute in the 1990s, and with his help I found it in a video store and purchased a copy. The whole series is in five video tapes.  Here I’ve extracted the episode of Cajal demonstrating to the leading German anatomists his Golgi-stained neurons at the 1889 meeting of the German Anatomical Society, which shows in dramatic fashion his personal breakthrough on the world stage and the beginnings of modern studies of the nervous system at the cellular level.

The historical context for this breakthrough is explained in Foundations of the Neuron Doctrine (Shepherd, 1991).  In the late 1880s Cajal published a flood of papers with his newly discovered Golgi method and sent them to the leading anatomists but no one responded.  He realized his only hope was to confront them with his slides, and determined to do that at the next meeting of the German Anatomical Society in October 1889 in Berlin.  Note in the video, that although Cajal did not speak German, he spoke to Kolliker in his limited French; Kolliker communicated with his colleagues in German.

The Berlin Meeting, 1889

The Spanish TV series is remarkably accurate in its representation of the Berlin meeting and of Cajal and the leading anatomists who took part; it’s as if a Spanish video team was there recording the event (!). On the first day Cajal has his slides ready but nobody shows any interest.  The second day begins in the same way.  Desperate, he heads directly for Albert Kolliker, the leading anatomist of that era, and pleads with him to come see his slides.  Kolliker, then approaching 80, agrees.  Other luminaries gather round: the bearded Waldeyer, who will formulate the Neuron Doctrine; clean-shaven Retzius of Sweden; Van Gehuchten of Belgium who with Cajal will formulate the concept of the Dynamic Polarization of the Neuron ….
 
Kolliker already had visited Golgi to see the new method for himself, and knew the potential but also that the impregnation was erratic. He looks through the microscope and quickly realizes he is seeing consistently beautiful Golgi impregnated nerve cells.  He looks at “Cayal” in astonishment; he signals for another slide, and another.  Finally, he stands and announces: “meine Herren, meine Herren … Mister Cayal has opened a new era in visualizing nerve cells”.  Congratulations flow.  … an orchestra swells the music … Cajal realizes he has achieved his dream …modern neuroscience is launched.

GM Shepherd, 10-3-2019
Cajal at the Berlin Meeting, 1889

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Cajal at the Berlin Meeting, 1889

Acknowledgment

“Ramon y Cajal”, episode 7, extracted from the final 6:32 minutes;

From a multi-episode “Life of Ramon y Cajal” shown on Spanish television in 1982.

Editado por METRO VIDEO ESPANOLA, S.L., Diseno IMASOL

distribuido por METRO VIDEO ESPANOLA, S.L.

C/ Torres Quevedo, 1 – Parque Tecnológico de Madrid

28760 TRES CANTOS (Madrid)

Video by Life of Ramon y Cajal