Biomedical subjects

Gero Miesenböck

Publications and source records attributed to Gero Miesenböck.

8 recordsLinked to original sources

PubMed2006

Next-generation optical technologies for illuminating genetically targeted brain circuits.

Emerging technologies from optics, genetics, and bioengineering are being combined for studies of intact neural circuits. The rapid progression of such interdisciplinary "optogenetic" approaches has expanded capabilities for optical imaging and genetic targeting of specific cell types. Here we explore key recent advances that unite optical and genetic approaches, focusing on promising techniques that either allow novel studies of neural dynamics and behavior or provide fresh perspectives on classic model systems.

Animals↗

PubMed2005

Remote control of behavior through genetically targeted photostimulation of neurons.

Optically gated ion channels were expressed in circumscribed groups of neurons in the Drosophila CNS so that broad illumination of flies evoked action potentials only in genetically designated target cells. Flies harboring the "phototriggers" in different sets of neurons responded to laser light with behaviors specific to the sites of phototrigger expression. Photostimulation of neurons in the giant fiber system elicited the characteristic escape behaviors of jumping, wing beating, and flight; photostimulation of dopaminergic neurons caused changes in locomotor activity and locomotor patterns. These responses reflected the direct optical activation of central neuronal targets rather than confounding visual input, as they persisted unabated in carriers of a mutation that eliminates phototransduction. Encodable phototriggers provide noninvasive control interfaces for studying the connectivity and dynamics of neural circuits, for assigning behavioral content to neurons and their activity patterns, and, potentially, for restoring information corrupted by injury or disease.

Action Potentials↗

PubMed2005

New technologies.

Explore the source record for details and available documents.

Biomedical Technology↗

PubMed2005

Optical imaging and control of genetically designated neurons in functioning circuits.

Proteins with engineered sensitivities to light are infiltrating the biological mechanisms by which neurons generate and detect electrochemical signals. Encoded in DNA and active only in genetically specified target cells, these proteins provide selective optical interfaces for observing and controlling signaling by defined groups of neurons in functioning circuits, in vitro and in vivo. Light-emitting sensors of neuronal activity (reporting calcium increase, neurotransmitter release, or membrane depolarization) have begun to reveal how information is represented by neuronal assemblies, and how these representations are transformed during the computations that inform behavior. Light-driven actuators control the electrical activities of central neurons in freely moving animals and establish causal connections between the activation of specific neurons and the expression of particular behaviors. Anchored within mathematical systems and control theory, the combination of finely resolved optical field sensing and finely resolved optical field actuation will open new dimensions for the analysis of the connectivity, dynamics, and plasticity of neuronal circuits, and perhaps even for replacing lost--or designing novel--functionalities.

Animals↗

PubMed2004

Video-rate nonlinear microscopy of neuronal membrane dynamics with genetically encoded probes.

Biological membranes decorated with suitable contrast agents give rise to nonlinear optical signals such as two-photon fluorescence and harmonic up-conversion when illuminated with ultra-short, high-intensity pulses of infrared laser light. Microscopic images based on these nonlinear contrasts were acquired at video or higher frame rates by scanning a focused illuminating spot rapidly across neural tissues. The scan engine relied on an acousto-optic deflector (AOD) to produce a fast horizontal raster and on corrective prisms to offset the AOD-induced dispersion of the ultra-short excitation light pulses in space and time. Two membrane-bound derivatives of the green fluorescent protein (GFP) were tested as nonlinear contrast agents. Synapto-pHluorin, a pH-sensitive GFP variant fused to a synaptic vesicle membrane protein, provided a time-resolved fluorescent read-out of neurotransmitter release at genetically specified synaptic terminals in the intact brain. Arrays of dually lipidated GFP molecules at the plasma membrane generated intense two-photon fluorescence but no detectable second-harmonic power. Comparison with second-harmonic generation by membranes stained with a synthetic styryl dye suggested that the genetically encoded chromophore arrangement lacked the orientational anisotropy and/or dipole density required for efficient coherent scattering of the incident optical field.

Animals↗

PubMed2004

Genetic methods for illuminating the function of neural circuits.

Guided by the notion that biology itself offers some of the most incisive tools for studying biological systems, neurophysiologists rely increasingly on cell biological mechanisms and materials encoded in DNA to visualize and control the activity of neurons in functional circuits. Optical reporter proteins can broadcast the operational states of genetically designated cells and synapses; remote-controlled effectors can suppress or induce electrical activity. Many challenges, however, remain. These include the development of novel gene expression systems that target reporters and effectors to functionally relevant neuronal ensembles, the capacity to monitor and manipulate multiple populations of neurons in parallel, the ability to observe and elicit precisely timed action potentials, and the power to communicate with genetically designated target neurons through electromagnetic signals other than light.

Action Potentials↗

PubMed2002

Transmission of olfactory information between three populations of neurons in the antennal lobe of the fly.

Three classes of neurons form synapses in the antennal lobe of Drosophila, the insect counterpart of the vertebrate olfactory bulb: olfactory receptor neurons, projection neurons, and inhibitory local interneurons. We have targeted a genetically encoded optical reporter of synaptic transmission to each of these classes of neurons and visualized population responses to natural odors. The activation of an odor-specific ensemble of olfactory receptor neurons leads to the activation of a symmetric ensemble of projection neurons across the glomerular synaptic relay. Virtually all excited glomeruli receive inhibitory input from local interneurons. The extent, odor specificity, and partly interglomerular origin of this input suggest that inhibitory circuits assemble combinatorially during odor presentations. These circuits may serve as dynamic templates that extract higher order features from afferent activity patterns.

Animals↗

PubMed2002

Selective photostimulation of genetically chARGed neurons.

To permit direct functional analyses of neural circuits, we have developed a method for stimulating groups of genetically designated neurons optically. Coexpression of the Drosophila photoreceptor genes encoding arrestin-2, rhodopsin (formed by liganding opsin with retinal), and the alpha subunit of the cognate heterotrimeric G protein--an explosive combination we term "chARGe"--sensitizes generalist vertebrate neurons to light. Illumination of a mixed population of neurons elicits action potentials selectively and cell-autonomously in its genetically chARGed members. In contrast to bath-applied photostimulants or caged neurotransmitters, which act indiscriminately throughout the illuminated volume, chARGe localizes the responsiveness to light. Distributed activity may thus be fed directly into a circumscribed population of neurons in intact tissue, irrespective of the spatial arrangement of its elements.

Action Potentials↗