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Research Description
Guided by the notion that biology itself offers some of the most incisive tools for studying biological systems, we rely on basic cellular mechanisms and materials encoded in DNA to record and remote-control the activity of nerve cells in the living brain. Our interests lie at the interface between cellular and systems neuroscience: we aim to understand how excitable cells are arranged into functional circuits, and how the operation of these circuits informs behavior.
To illuminate circuit mechanisms, we study explants of mouse brains in which specific classes of neurons have been programmed genetically to be light-addressable. This allows us to feed artificial ‘test patterns’ into the circuitry and trace the transformations of these patterns in optical or electrophysiological recordings, with the intent of revealing the underlying information-processing architectures and computational principles.
To relate circuit states to behavior, we work with another genetically tractable model organism, the fruit fly. We observe or induce changes in the physiological states of genetically defined groups of neurons in the intact fly brain and correlate them with behavioral states to decipher the neural signals used to represent ‘content’.
Selected recent publications:
Miesenböck, G., D.A. De Angelis and J.E. Rothman (1998) Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature 394: 192-195.
Zemelman, B.V., G.A. Lee, M. Ng and G. Miesenböck (2002) Selective photostimulation of genetically chARGed neurons. Neuron 33: 15-22.
Ng, M., R.D. Roorda, S.Q. Lima, B.V. Zemelman, P. Morcillo and G. Miesenböck (2002) Transmission of olfactory information between three populations of neurons in the antennal lobe of the fly. Neuron 36: 463-474.
Zemelman, B.V., N. Nesnas, G.A. Lee and G. Miesenböck (2003) Photochemical gating of heterologous ion channels: Remote control over genetically designated populations of neurons. Proc. Natl. Acad. Sci. USA 100: 1352-1357.
Roorda, R.D., T.M. Hohl, R. Toledo-Crow and G. Miesenböck (2004) Video-rate nonlinear microscopy of neuronal membrane dynamics with genetically encoded probes. J. Neurophysiol. 92: 609-621.
Miesenböck, G. (2004) Genetic methods for illuminating the function of neural circuits. Curr. Opin. Neurobiol. 14: 395-402.
Lima, S.Q. and G. Miesenböck (2005) Remote control of behavior through genetically targeted photostimulation of neurons. Cell 121: 141-152.
Miesenböck, G. and I.G. Kevrekidis (2005) Optical imaging and control of genetically designated neurons in functioning circuits. Annu. Rev. Neurosci 28: 533-563.
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