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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: 14.98). 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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    • "Mapping the brain-wide effects of such stimulations is crucial for understanding the link between behavioral output and activated circuits. This is of special relevance in mice, where a broad range of tools has become available for optogenetic stimulations (Boyden et al., 2005; Yizhar et al., 2011). Given the increasing number of such studies methods that can image animals at high throughput will be of particular interest. "
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    ABSTRACT: Electrical and optogenetic methods for brain stimulation are widely used in rodents for manipulating behavior and analyzing functional connectivities in neuronal circuits. High-resolution in vivo imaging of the global, brain-wide, activation patterns induced by these stimulations has remained challenging, in particular in awake behaving mice. We here mapped brain activation patterns in awake, intracranially self-stimulating mice using a novel protocol for single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (rCBF). Mice were implanted with either electrodes for electrical stimulation of the medial forebrain bundle (mfb-microstim) or with optical fibers for blue-light stimulation of channelrhodopsin-2 expressing neurons in the ventral tegmental area (vta-optostim). After training for self-stimulation by current or light application, respectively, mice were implanted with jugular vein catheters and intravenously injected with the flow tracer 99m-technetium hexamethylpropyleneamine oxime (99mTc-HMPAO) during seven to ten minutes of intracranial self-stimulation or ongoing behavior without stimulation. The 99mTc-brain distributions were mapped in anesthetized animals after stimulation using multipinhole SPECT. Upon self-stimulation rCBF strongly increased at the electrode tip in mfb-microstim mice. In vta-optostim mice peak activations were found outside the stimulation site. Partly overlapping brain-wide networks of activations and deactivations were found in both groups. When testing all self-stimulating mice against all controls highly significant activations were found in the rostromedial nucleus accumbens shell. SPECT-imaging of rCBF using intravenous tracer-injection during ongoing behavior is a new tool for imaging regional brain activation patterns in awake behaving rodents providing higher spatial and temporal resolutions than 18F-2-fluoro-2-dexoyglucose positron emission tomography.
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