Development and function of the cortical microcircuitry.
Cortical Circuits and Dendritic Spines
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 accepted unitary theory of cortical function exists yet; nevertheless, the basic cortical microcircuitry develops in stereotyped fashion, is similar in different cortical areas and in different species, and has apparently 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 exist and implement a relatively simple, and flexible, computation.
We attempt to reverse-engineer the cortical microcircuit using brain slices from mouse neocortex as our experimental preparation. The techniques applied are electrophysiology, anatomy, and a variety of optical methods, including infrared-DIC, voltage- and ion-sensitive dye imaging with confocal, two-photon and second harmonic microscopy. We also use laser uncaging, biolistics, electroporation, electron microscopy and numerical simulations, and make extensive use of genetically modified mouse strains.
We focus on two major 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. Recent data indicates that spines can serve as electrical compartments and that can linearize input summation, indicating that cortical circuits could be essentially linear networks. Also, spines exhibit rapid morphological plasticity, raising 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 that may represent a functional state of the circuit, such as an attractor. Optical imaging of populations of cells make it possible to visualize circuit dynamics, deduce its potential circuit architecture and explore if canonical microcircuits exist. We are also interested in understanding how epileptic seizures can recruit apparently normal cortical circuits.
- Fino, E. and Yuste, R. (2011) Dense inhibitory connectivity in neocortex. Neuron 69: 1188-1203. Article
- Peterka, D., Takahashi, H., and Yuste, R. (2011) Imaging Voltage in Neurons. Neuron 69: 9-21. Article
- Yuste, R. (2010) Dendritic Spines. MIT Press Article
- Yuste, R., Ed. (2010) Imaging: A Laboratory Manual. Cold Spring Harbor Press Article
- Yuste, R. (2008) Circuit neuroscience: the road ahead. Frontiers in Neuroscience 2,1: 6-9.. Article
- Ascoli, G., et al (2008) Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nature Reviews Neuroscience 9: 557-568. Article
- Nikolenko, V., Poskanzer, K. and Yuste R. (2007) Two-photon photostimulation and imaging of neural circuits. Nature Methods 4: 943 - 950.
- Nikolenko, V., Eisenthal, K.B. and Yuste, R. (2007) Sodium channels amplify spine potentials. Proc. Natl. Acad. Sci. USA 104: 12347-52.
- Nuriya, M., Jian,g J., Nemet, B., Eisenthal, K. B. and Yuste, R. (2006) Imaging membrane potential in dendritic spines. PNAS 103: 786-790. Article
- Araya, R., Jiang, J., Eisenthal, K. B. and Yuste, R. (2006) The spine neck filters membrane potentials. PNAS 17961-17966. Article
- Araya, R., Eisenthal, K. B. and Yuste, R. (2006) Dendritic spines linearize the summation of excitatory potentials PNAS 10: 1073. Article
- McLean, J. A, Fenstermaker, V., Watson, B. O. and Yuste R. (2006) A visual thalamocortical slice. Nature Methods 3: 129-134.
- MacLean, J., Watson, B., Aaron, G. and Yuste, R. (2005) Internal Dynamics Determine the Cortical Response to Thalamic Stimulation. Neuron 48: 811-823. Article
- Yuste, R. (2005) Fluorescence microscopy today Nature Meth 2: 902-4.
- Yuste, R. (2005) Origin and classification of neocortical interneurons. Neuron 48: 524-7.
- Yuste, R. and Konnerth, A. (2005) Imaging in Neuroscience and Development: a Laboratory Manua Cold Spring Harbor Press Article
- Yuste, R., MacLean, J.N., Smith, J., Lansner, A. (2005) The cortex as a central pattern generator. Nature Rev. Neurosci. 6: 477-483.
- MacLean J., Watson B., Aaron G., and Yuste R. (2005) Internal Dynamics Determine the Cortical Response to Thalamic Stimulation. Neuron 48: 811–823. Article
- 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. Article
- Yuste, R. and Bonhoeffer, T. (2004) Genesis of dendritic spines: insights from ultrastructural and imaging studies. Nature Neurosci. Rev. 5: 24-34.
- Cossart R, Aronov D, Yuste R. (2003) Attractor dynamics of network UP states in the neocortex Nature 423: 283-8. Article
- Goldberg, J., Tamas, G., Aronov, D. and Yuste, R (2003) Calcium microdomains in aspiny dendrites. Neuron 40: 807-821.
- Tashiro, A., Dunaevsky, A., Blazeski, R., Mason, C.A. and Yuste, R. (2003) Bidirectional regulation of hippocampal mossy fiber filopodial motility by kainate receptors: a two-step model of synaptogenesis. Neuron 38: 773-784.
- Bonhoeffer, T. and Yuste, R. (2002) Spine motility: Phenomenology, Mechanisms and Function Neuron 35: 1019-1027.
- Holthoff, K., Tsay, D. and Yuste, R. (2002) Calcium dynamics in spines depend on their dendritic position Neuron 33: 425-437.
- Yuste, R. and Bonhoeffer, T. (2001) Morphological changes in dendritic spines associated with long-term synaptic plasticity Ann. Rev. Neurosci. 24: 1071-89.
- Kozloski J, Hamzei-Sichani F, Yuste R. (2001) Stereotyped position of local synaptic targets in neocortex Science 293(5531): 868-72. Article
- Mao BQ, Hamzei-Sichani F, Aronov D, Froemke RC, and Yuste, R. (2001) Dynamics of spontaneous activity in neocortical slices Neuron 32: 883-898.
- Yuste, R., Majewska, A. and Holthoff, K. (2000) From form to function: calcium compartmentalization in dendritic spines Nature Neurosci 3(7): 653-659.
- Peterlin Z.A., Kozloski J., Mao B.Q., Tsiola A., Yuste R. (2000) Optical probing of neuronal circuits with calcium indicators Proc Natl Acad Sci USA 97(7): 3619-24.
- Yuste, R., Lanni, F. and Konnerth, A. (1999) Imaging Neurons: a Laboratory Manual Cold Spring Harbor Press Article
- Cash, S. and Yuste, R. (1999) Linear summation of excitatory inputs by CA1 pyramidal neurons. Neuron 22: 383-394. Article
- Dunaevsky, A., Tashiro, A. Majewska, A., Mason, C. A. and Yuste, R. (1999) Developmental regulation of spine motility in mammalian CNS. Proc. Natl. Acad. Sci. USA 96 (23): 13438-13443.
- Schwartz, T., Rabinowitz, D., Unni, V. K., Kumar, V. S., Smetters, D. K., Tsiola, A. and Yuste, R. (1998) Networks of coactive neurons in developing layer 1. Neuron 20: 1271-1283.
- Yuste, R and Simon, D. (1997) Barrels in the desert: Cortical circuits in Sde Boker Neuron 19: 231-237.
- Yuste, R. (1997) Potassium channels: dendritic shock absorbers. Nature 387: 851-53.
- Yuste, R. and Tank, D. W. (1996) Dendritic integration in mammalian neurons, a century after Cajal Neuron 16: 701-716. Article
- Yuste, R. and Denk, W. (1995) Dendritic spines as basic functional units of neuronal integration Nature 375: 682-684.
- Yuste, R., Nelson, D. A., Rubin, W. A. and Katz, L. C. (1995) Neuronal domains: Mechanisms of coactivation. Neuron 14: 1-11.
- Yuste, R., Gutnick, M. J., Saar, D., Delaney, K. and Tank, D. W. (1994) Calcium accumulations in neocortical cell dendrites: An apical band and evidence for functional compartments. Neuron 13: 23-43.
- Yuste, R., Peinado, A. and Katz L. C. (1992) Neuronal domains in developing neocortex Science 257: 665-669. Article
- Yuste, R. and Katz, L. C. (1991) Control of postsynaptic calcium influx in developing neocortex by excitatory and inhibitory neurotransmitters Neuron 6: 333-344.