Rafael Yuste

Howard Hughes Medical Institute
Columbia University
Biological Sciences
1002 Fairchild Center, M.C. 2435
New York, N.Y. 10027
rmy5@columbia.edu

Petilla Meeting

Philosophy-Neuroscience (Templeton) Seminars

Kavli Institute for Brain Science

Department of Neuroscience

Columbia Neuroscience

Biophysics and Biophysical Chemistry Program

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The goal of our laboratory is to understand the function of the cortical microcircuit. The cortex constitutes the larger part of the brain in mammals. In humans it is the primary site of mental functions like perception, memory, control of voluntary movements, imagination, language and music. No unitary theory of cortical function exists yet; nevertheless, the basic cortical microcircuitry develops in stereotyped fashion, is similar in different parts of the cortex and in different mammals, and has not changed much in evolution since its appearance. At the same time, the cortex participates in apparently widely different computational tasks, resembling a "Turing machine". Because of this, it is conceivable that a "canonical" cortical microcircuit may implement a relatively simple computation.

We use brain slices to study the cortical circuitry at the cellular and multicellular level. The techniques used are electrophysiology and a variety of optical methods, including infrared-DIC, voltage- and ion-sensitive dye imaging with cooled CCD cameras and two-photon microscopy. We also use biolistics transfection, electron microscopy and numerical simulations and modeling. We are focusing on two questions:

(1) What is the function of dendritic spines? Spines are an essential element in cortical circuits and are still poorly understood. Two-photon microscopy has enabled functional studies of dendritic spines and has shown that they compartmentalize calcium because of their morphological features and local calcium influx and efflux mechanisms. Spines have recently been shown to exhibit rapid morphological plasticity. This has raised the possibility that the function of the spine, or the synapse, is equally dynamic.

(2) What are the multicellular patterns of activity under spontaneous or evoked activation of the circuit? It is still unknown if adult cortical neurons respond individually, or if there are multicellular units of activation which may represent a functional state of the circuit, such as an attractor. Optical imaging of populations of cells may make it possible to visualize the circuit dynamics and explore if canonical microcircuits exist.

Representative Publications:


Yuste, R., Peinado, A. and Katz L. C. (1992). Neuronal domains in developing neocortex. Science 257: 665-669.Abstract

Yuste, R. and Denk, W. (1995). Dendritic spines as basic functional units of neuronal integration. Nature 375: 682-684.

Yuste, R. and Tank, D. W. (1996). Dendritic integration in mammalian neurons, a century after Cajal. Neuron 16: 701-716. Abstract

Cash, S. and Yuste, R. (1999). Linear summation of excitatory inputs by CA1 pyramidal neurons. Neuron 22, 383-394.

Yuste, R., Lanni, F. and Konnerth, A. (1999)."Imaging Neurons: a Laboratory Manual", Cold Spring Harbor Press

Kozloski J, Hamzei-Sichani F, Yuste R. (2001) Stereotyped position of local synaptic targets in neocortex.
Science. Aug 3;293(5531):868-72.  Abstract  |  Full text  |

Bonhoeffer, T. and Yuste, R. (2002). Spine motility: Phenomenology, Mechanisms and Function. Neuron 35, 1019­1027. Abstract  |  Full text  |

Cossart R, Aronov D, Yuste R. (2003). Attractor dynamics of network UP states in the neocortex. Nature. 423:283-8 Abstract  |  Full text  |

Ikegaya Y., Aaron G., Cossart R., Aronov D., Lampl I., Ferster D., Yuste R. (2004) Synfire Chains and Cortical Songs: Temporal Modules of Cortical Activity. Science. 304 (5670): 559-564. Abstract  |  Full text  |

MacLean J., Watson B., Aaron G., and Yuste R. (2005), Internal Dynamics Determine the Cortical Response to Thalamic Stimulation. Neuron 48: 811–823. Full text  | Press release.

Araya R., Jiang J., Eisenthal K. B., and Yuste R. (2006), The spine neck filters membrane potentials. PNAS 103: 17961-17966
Full text  | Press Release.

Araya R., Eisenthal K. B., and Yuste R. (2006), Dendritic spines linearize the summation of excitatory potentials. PNAS 10. 1073
Full text  |

Nuriya M., Jiang J., Nemet B., Eisenthal K. B., and Yuste R. (2006), Imaging membrane potential in dendritic spines. PNAS 103: 786-790
Full text  | Press release

 

Databases & Protocols

Neurolucida reconstructions

Library of Mouse Cortical Neurons

Circuit diagram of neocortical inhibitory interneurons (requires Flash)

Circuit diagram of neocortical excitory neurons (requires Flash)

Interneuron connection diagram based on published data (requires MS Power Point)

Lab Reprint Library (Password protected)

Gray Library (lab members only)

Building a two-photon microscope:

"A custom-made two-photon microscope and deconvolution system"

External PMt amplifier info

A custom two-photon and second-harmonic microscope

Genegun transfection in mice slice cultures:

"Regulation of Dendritic Spine Morphology by the Rho Family of GTPases: Antagonistic Roles of Rac and Rho"

Imaging action potentials in neuronal populations:

"Detecting Action Potentials in Neuronal Populations with Calcium Imaging"

Optical probing of circuits:

"Optical probing of neuronal circuits with calcium indicators"

 

"Reverse optical probing (ROPING) of neocortical circuits "

 

 

Courses Taught:

Course Number

Title

W4011

Neural Systems: Circuits in the Brain

W4070

Readings in Biophysics: from Single Molecules to Networks

V3654

Philosophy of Psychology (no course webpage)

W3004

Neurobiology I

W3005

Neurobiology II

G4008y

Advanced Seminar in Neurobiology: Dendritic Integration

G9010

Neural Bases of Behavior: Neuroethological Approaches

 

Lab Members

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