Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8: 1263-1268

Department of Bioengineering, Stanford University, 318 Campus Drive West, Stanford, California 94305, USA.
Nature Neuroscience (Impact Factor: 16.1). 10/2005; 8(9):1263-8. DOI: 10.1038/nn1525
Source: PubMed

ABSTRACT Temporally precise, noninvasive control of activity in well-defined neuronal populations is a long-sought goal of systems neuroscience. We adapted for this purpose the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons. We demonstrate reliable, millisecond-timescale control of neuronal spiking, as well as control of excitatory and inhibitory synaptic transmission. This technology allows the use of light to alter neural processing at the level of single spikes and synaptic events, yielding a widely applicable tool for neuroscientists and biomedical engineers.

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    • "Bursting synchronisation appears between neurons in the auditory region when an external perturbation is applied in another cognitive area. We consider perturbations that activate neurons in accordance with experimental results in that pulses of blue light are capable to induce neuronal spikes [26] [27]. This paper is organised as follows: in Section II we introduce the network of Rulkov neurons and the cat brain matrix. "
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    ABSTRACT: The brain of mammals are divided into different cortical areas that are anatomically connected forming larger networks which perform cognitive tasks. The cat cerebral cortex is composed of 65 areas organised into the visual, auditory, somatosensory-motor and frontolimbic cognitive regions. We have built a network of networks, in which networks are connected among themselves according to the connections observed in the cat cortical areas aiming to study how inputs drive the synchronous behaviour in this cat brain-like network. We show that without external perturbations it is possible to observe high level of bursting synchronisation between neurons within almost all areas, except for the auditory area. Bursting synchronisation appears between neurons in the auditory region when an external perturbation is applied in another cognitive area. This is a clear evidence that pattern formation and collective behaviour in the brain might be a process mediated by other brain areas under stimulation.
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    • "Functional neural networks can be identified with techniques involving genetically encoded effectors for activating and inhibiting specific neuronal populations [28]. Emerging tools for defining cellspecific anatomical connections and functional networks include light-activated channels ('optogenetics'; [29]) or receptors activated by inert ligands ('pharmacogenetics' [30]). These techniques have helped determine the neural circuits that regulate behaviors such as appetite [31]. "
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    ABSTRACT: The autonomic nervous system affects glucose metabolism partly through its connection to the pancreatic islet. Since its discovery by Paul Langerhans, the precise innervation patterns of the islet has remained elusive, mainly because of technical limitations. Using 3-dimensional reconstructions of axonal terminal fields, recent studies have determined the innervation patterns of mouse and human islets. In contrast to the mouse islet, endocrine cells within the human islet are sparsely contacted by autonomic axons. Instead, the invading sympathetic axons preferentially innervate smooth muscle cells of blood vessels. This innervation pattern suggests that, rather than acting directly on endocrine cells, sympathetic nerves may control hormone secretion by modulating blood flow in human islets. In addition to autonomic efferent axons, islets also receive sensory innervation. These axons transmit sensory information to the brain but also have the ability to locally release neuroactive substances that have been suggested to promote diabetes pathogenesis. We discuss recent findings on islet innervation, the connections of the islet with the brain, and the role islet innervation plays during the progression of diabetes.
    Best Practice & Research: Clinical Endocrinology & Metabolism 10/2014; 28(5). DOI:10.1016/j.beem.2014.05.002 · 4.60 Impact Factor
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    • "Optogenetics is now a decade old genetic manipulation technique which can render nerve cells light sensitive [4]. The great advantages of the technique has been to provide genetically targeted excitatory [5] and inhibitory [6] control of neural circuitry with millisecond precision. The key issue for the neuroprosthesis community has been an intense light requirement of typically 1015–1019 photons/cm2 at 480 nm (instantaneous pulsed irradiance) [7], [8] which is close to the photochemical damage threshold of nerve cells [9], but also makes it challenging to create stimulation optoelectronics. "
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    ABSTRACT: In the modern view of synaptic transmission, astrocytes are no longer confined to the role of merely supportive cells. Although they do not generate action potentials, they nonetheless exhibit electrical activity and can influence surrounding neurons through gliotransmitter release. In this work, we explored whether optogenetic activation of glial cells could act as an amplification mechanism to optical neural stimulation via gliotransmission to the neural network. We studied the modulation of gliotransmission by selective photo-activation of channelrhodopsin-2 (ChR2) and by means of a matrix of individually addressable super-bright microLEDs (mu LEDs) with an excitation peak at 470 nm. We combined Ca2+ imaging techniques and concurrent patch-clamp electrophysiology to obtain subsequent glia/neural activity. First, we tested the mu LEDs efficacy in stimulating ChR2-transfected astrocyte. ChR2-induced astrocytic current did not desensitize overtime, and was linearly increased and prolonged by increasing mu LED irradiance in terms of intensity and surface illumination. Subsequently, ChR2 astrocytic stimulation by broad-field LED illumination with the same spectral profile, increased both glial cells and neuronal calcium transient frequency and sEPSCs suggesting that few ChR2-transfected astrocytes were able to excite surrounding not-ChR2-transfected astrocytes and neurons. Finally, by using the mu LEDs array to selectively light stimulate ChR2 positive astrocytes we were able to increase the synaptic activity of single neurons surrounding it. In conclusion, ChR2-transfected astrocytes and mu LEDs system were shown to be an amplifier of synaptic activity in mixed corticalneuronal and glial cells culture.
    PLoS ONE 09/2014; 9(9). DOI:10.1371/journal.pone.0108689 · 3.23 Impact Factor
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