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  • 1
    In: Cell Reports, Elsevier BV, Vol. 28, No. 13 ( 2019-09), p. 3450-3461.e8
    Type of Medium: Online Resource
    ISSN: 2211-1247
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 2649101-1
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  • 2
    Online Resource
    Online Resource
    American Medical Association (AMA) ; 2015
    In:  JAMA Vol. 313, No. 20 ( 2015-05-26), p. 2019-
    In: JAMA, American Medical Association (AMA), Vol. 313, No. 20 ( 2015-05-26), p. 2019-
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2015
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 3
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2010
    In:  Neurosurgery Vol. 67, No. 2 ( 2010-08), p. 557-
    In: Neurosurgery, Ovid Technologies (Wolters Kluwer Health), Vol. 67, No. 2 ( 2010-08), p. 557-
    Type of Medium: Online Resource
    ISSN: 0148-396X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2010
    detail.hit.zdb_id: 1491894-8
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  • 4
    In: Stem Cells, Oxford University Press (OUP), Vol. 29, No. 1 ( 2011-01-01), p. 78-88
    Abstract: Membrane depolarization has been shown to play an important role in the neural differentiation of stem cells and in the survival and function of mature neurons. Here, we introduce a microbial opsin into ESCs and develop optogenetic technology for stem cell engineering applications, with an automated system for noninvasive modulation of ESC differentiation employing fast optogenetic control of ion flux. Mouse ESCs were stably transduced with channelrhodopsin-2 (ChR2)-yellow fluorescent protein and purified by fluorescence activated cell sorting (FACS). Illumination of resulting ChR2-ESCs with pulses of blue light triggered inward currents. These labeled ESCs retained the capability to differentiate into functional mature neurons, assessed by the presence of voltage-gated sodium currents, action potentials, fast excitatory synaptic transmission, and expression of mature neuronal proteins and neuronal morphology. We designed and tested an apparatus for optically stimulating ChR2-ESCs during chronic neuronal differentiation, with high-speed optical switching on a custom robotic stage with environmental chamber for automated stimulation and imaging over days, with tracking for increased expression of neural and neuronal markers. These data point to potential uses of ChR2 technology for chronic and temporally precise noninvasive optical control of ESCs both in vitro and in vivo, ranging from noninvasive control of stem cell differentiation to causal assessment of the specific contribution of transplanted cells to tissue and network function.
    Type of Medium: Online Resource
    ISSN: 1066-5099 , 1549-4918
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2011
    detail.hit.zdb_id: 2030643-X
    detail.hit.zdb_id: 1143556-2
    detail.hit.zdb_id: 605570-9
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2011
    In:  Biophysical Journal Vol. 100, No. 3 ( 2011-02), p. 368a-
    In: Biophysical Journal, Elsevier BV, Vol. 100, No. 3 ( 2011-02), p. 368a-
    Type of Medium: Online Resource
    ISSN: 0006-3495
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
    detail.hit.zdb_id: 1477214-0
    SSG: 12
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  • 6
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 33, No. 17 ( 2013-04-24), p. 7393-7406
    Abstract: In Huntington's disease (HD) mouse models, spontaneous inhibitory synaptic activity is enhanced in a subpopulation of medium-sized spiny neurons (MSNs), which could dampen striatal output. We examined the potential source(s) of increased inhibition using electrophysiological and optogenetic methods to assess feedback and feedforward inhibition in two transgenic mouse models of HD. Single whole-cell patch-clamp recordings demonstrated that increased GABA synaptic activity impinges principally on indirect pathway MSNs. Dual patch recordings between MSNs demonstrated reduced connectivity between MSNs in HD mice. However, while connectivity was strictly unidirectional in controls, in HD mice bidirectional connectivity occurred. Other sources of increased GABA activity in MSNs also were identified. Dual patch recordings from fast spiking (FS) interneuron–MSN pairs demonstrated greater but variable amplitude responses in MSNs. In agreement, selective optogenetic stimulation of parvalbumin-expressing, FS interneurons induced significantly larger amplitude MSN responses in HD compared with control mice. While there were no differences in responses of MSNs evoked by activating single persistent low-threshold spiking (PLTS) interneurons in recorded pairs, these interneurons fired more action potentials in both HD models, providing another source for increased frequency of spontaneous GABA synaptic activity in MSNs. Selective optogenetic stimulation of somatostatin-expressing, PLTS interneurons did not reveal any significant differences in responses of MSNs in HD mice. These findings provide strong evidence that both feedforward and to a lesser extent feedback inhibition to MSNs in HD can potentially be sources for the increased GABA synaptic activity of indirect pathway MSNs.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2013
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 7
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 33, No. 18 ( 2013-05-01), p. 7618-7626
    Abstract: The lateral hypothalamus (LH) sends a dense glutamatergic and peptidergic projection to dopamine neurons in the ventral tegmental area (VTA), a cell group known to promote reinforcement and aspects of reward. The role of the LH to VTA projection in reward-seeking behavior can be informed by using optogenetic techniques to dissociate the actions of LH neurons from those of other descending forebrain inputs to the VTA. In the present study, we identify the effect of neurotensin (NT), one of the most abundant peptides in the LH to VTA projection, on excitatory synaptic transmission in the VTA and reward-seeking behavior. Mice displayed robust intracranial self-stimulation of LH to VTA fibers, an operant behavior mediated by NT 1 receptors (Nts1) and NMDA receptors. Whole-cell patch-clamp recordings of VTA dopamine neurons demonstrated that NT (10 n m ) potentiated NMDA-mediated EPSCs via Nts1. Results suggest that NT release from the LH into the VTA activates Nts1, thereby potentiating NMDA-mediated EPSCs and promoting reward. The striking behavioral and electrophysiological effects of NT and glutamate highlight the LH to VTA pathway as an important component of reward.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2013
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Society for Neuroscience ; 2015
    In:  The Journal of Neuroscience Vol. 35, No. 41 ( 2015-10-14), p. 13917-13926
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 35, No. 41 ( 2015-10-14), p. 13917-13926
    Abstract: There have been two recent revolutionary advances in neuroscience: First, genetically encoded activity sensors have brought the goal of optical detection of single action potentials in vivo within reach. Second, optogenetic actuators now allow the activity of neurons to be controlled with millisecond precision. These revolutions have now been combined, together with advanced microscopies, to allow “all-optical” readout and manipulation of activity in neural circuits with single-spike and single-neuron precision. This is a transformational advance that will open new frontiers in neuroscience research. Harnessing the power of light in the all-optical approach requires coexpression of genetically encoded activity sensors and optogenetic probes in the same neurons, as well as the ability to simultaneously target and record the light from the selected neurons. It has recently become possible to combine sensors and optical strategies that are sufficiently sensitive and cross talk free to enable single-action-potential sensitivity and precision for both readout and manipulation in the intact brain. The combination of simultaneous readout and manipulation from the same genetically defined cells will enable a wide range of new experiments as well as inspire new technologies for interacting with the brain. The advances described in this review herald a future where the traditional tools used for generations by physiologists to study and interact with the brain—stimulation and recording electrodes—can largely be replaced by light. We outline potential future developments in this field and discuss how the all-optical strategy can be applied to solve fundamental problems in neuroscience. SIGNIFICANCE STATEMENT This review describes the nexus of dramatic recent developments in optogenetic probes, genetically encoded activity sensors, and novel microscopies, which together allow the activity of neural circuits to be recorded and manipulated entirely using light. The optical and protein engineering strategies that form the basis of this “all-optical” approach are now sufficiently advanced to enable single-neuron and single-action potential precision for simultaneous readout and manipulation from the same functionally defined neurons in the intact brain. These advances promise to illuminate many fundamental challenges in neuroscience, including transforming our search for the neural code and the links between neural circuit activity and behavior.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2015
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 9
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 20, No. 1 ( 2000-01-01), p. 266-273
    Abstract: Activity-dependent gene expression in neurons shows a remarkable ability to differentiate between different types of stimulation: orthodromic inputs that engage synaptic transmission are much more effective than antidromic stimuli that do not. We have studied the basis of such selectivity in cultured hippocampal neurons in which nuclear cAMP response element-binding protein (CREB) phosphorylation is induced by synaptic activity but not by action potential (AP) stimulation in the absence of EPSPs, although spikes by themselves generate large elevations in intracellular Ca 2+ . Previous work has shown that Ca 2+ entry through L-type Ca 2+ channels plays a dominant role in triggering calmodulin mobilization and activation of calmodulin-dependent kinases that phosphorylate CREB, raising the possibility that L-type channels contribute to the selective response to EPSPs rather than APs. Accordingly, we performed voltage-clamp experiments to compare the currents carried by L-type channels during depolarizing waveforms that approximated APs or dendritic EPSPs. The integrated current generated by L-type channels was significantly less after mock APs than with EPSP-like depolarizations. The difference was traced to two distinct factors. Compared with other channels, L-type channels activated at relatively negative potentials, favoring their opening with EPSP stimulation; they also exhibited relatively slow activation kinetics, weighing against their contribution during an AP. The relative ineffectiveness of APs as a stimulus for CREB phosphorylation could be overcome by exposure to the agonist Bay K8644, which potentiated the AP-induced influx through L-type channels by ∼10-fold. Under normal conditions, the unique biophysical properties of L-type channels allow them to act as a kinetic filter to support spike–EPSP discrimination.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2000
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2007
    In:  Science Vol. 317, No. 5839 ( 2007-08-10), p. 819-823
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 317, No. 5839 ( 2007-08-10), p. 819-823
    Abstract: The hippocampus is one of several brain areas thought to play a central role in affective behaviors, but the underlying local network dynamics are not understood. We used quantitative voltage-sensitive dye imaging to probe hippocampal dynamics with millisecond resolution in brain slices after bidirectional modulation of affective state in rat models of depression. We found that a simple measure of real-time activity—stimulus-evoked percolation of activity through the dentate gyrus relative to the hippocampal output subfield—accounted for induced changes in animal behavior independent of the underlying mechanism of action of the treatments. Our results define a circuit-level neurophysiological endophenotype for affective behavior and suggest an approach to understanding circuit-level substrates underlying psychiatric disease symptoms.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2007
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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