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Optogenetics and behavior

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https://www.readbyqxmd.com/read/29027111/excessive-d1-dopamine-receptor-activation-in-the-dorsal-striatum-promotes-autistic-like-behaviors
#1
Yunjin Lee, Hannah Kim, Ji-Eun Kim, Jin-Young Park, Juli Choi, Jung-Eun Lee, Eun-Hwa Lee, Pyung-Lim Han
The dopamine system has been characterized in motor function, goal-directed behaviors, and rewards. Recent studies recognize various dopamine system genes as being associated with autism spectrum disorder (ASD). However, how dopamine system dysfunction induces ASD pathophysiology remains unknown. In the present study, we demonstrated that mice with increased dopamine functions in the dorsal striatum via the suppression of dopamine transporter expression in substantia nigra neurons or the optogenetic stimulation of the nigro-striatal circuitry exhibited sociability deficits and repetitive behaviors relevant to ASD pathology in animal models, while these behavioral changes were blocked by a D1 receptor antagonist...
October 12, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29024604/the-avian-embryo-as-a-model-for-fetal-alcohol-spectrum-disorders
#2
Susan M Smith, George R Flentke
Prenatal alcohol exposure (PAE) remains a leading preventable cause of structural birth defects and permanent neurodevelopmental disability. The chick (Gallus gallus domesticus) is a powerful embryological research model and was possibly the first (Fere, 1895) in which alcohol's teratogenicity was demonstrated. Pharmacologically relevant alcohol exposures in the range of 20-70 mM (20-80 mg/egg) disrupt chick embryo growth, morphogenesis, and behavior, and the resulting phenotypes strongly parallel those of mammalian models...
October 12, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29021994/stereotaxic-adeno-associated-virus-injection-and-cannula-implantation-in-the-dorsal-raphe-nucleus-of-mice
#3
Patrícia A Correia, Sara Matias, Zachary F Mainen
Optogenetic methods are now widespread in neuroscience research. Here we present a detailed surgical procedure to inject adeno-associated viruses and implant optic fiber cannulas in the dorsal raphe nucleus (DRN) of living mice. Combined with transgenic mouse lines, this protocol allows specific targeting of serotonin-producing neurons in the brain. It includes fixing a mouse in a stereotaxic frame, performing a craniotomy, virus injection and fiber implantation. Animals can be later used in behavioral experiments, combined with optogenetic manipulations (Dugué et al...
September 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28994798/large-volume-behaviorally-relevant-illumination-for-optogenetics-in-non-human-primates
#4
Leah C Acker, Erica N Pino, Edward S Boyden, Robert Desimone
This protocol describes a large-volume illuminator, which was developed for optogenetic manipulations in the non-human primate brain. The illuminator is a modified plastic optical fiber with etched tip, such that the light emitting surface area is > 100x that of a conventional fiber. In addition to describing the construction of the large-volume illuminator, this protocol details the quality-control calibration used to ensure even light distribution. Further, this protocol describes techniques for inserting and removing the large volume illuminator...
October 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28986567/enhancing-excitatory-activity-of-somatosensory-cortex-alleviates-neuropathic-pain-through-regulating-homeostatic-plasticity
#5
Wenhui Xiong, Xingjie Ping, Matthew S Ripsch, Grace Santa Cruz Chavez, Heidi Elise Hannon, Kewen Jiang, Chunhui Bao, Vaishnavi Jadhav, Lifang Chen, Zhi Chai, Cungen Ma, Huangan Wu, Jianqiao Feng, Armin Blesch, Fletcher A White, Xiaoming Jin
Central sensitization and network hyperexcitability of the nociceptive system is a basic mechanism of neuropathic pain. We hypothesize that development of cortical hyperexcitability underlying neuropathic pain may involve homeostatic plasticity in response to lesion-induced somatosensory deprivation and activity loss, and can be controlled by enhancing cortical activity. In a mouse model of neuropathic pain, in vivo two-photon imaging and patch clamp recording showed initial loss and subsequent recovery and enhancement of spontaneous firings of somatosensory cortical pyramidal neurons...
October 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28980939/pedunculopontine-glutamatergic-neurons-control-spike-patterning-in-substantia-nigra-dopaminergic-neurons
#6
Daniel J Galtieri, Chad M Estep, David L Wokosin, Stephen Traynelis, D James Surmeier
Burst spiking in substantia nigra pars compacta (SNc) dopaminergic neurons is a key signaling event in the circuitry controlling goal-directed behavior. It is widely believed that this spiking mode depends upon an interaction between synaptic activation of N-methyl-D-aspartate receptors (NMDARs) and intrinsic oscillatory mechanisms. However, the role of specific neural networks in burst generation has not been defined. To begin filling this gap, SNc glutamatergic synapses arising from pedunculopotine nucleus (PPN) neurons were characterized using optical and electrophysiological approaches...
October 5, 2017: ELife
https://www.readbyqxmd.com/read/28973921/long-term-restoration-of-visual-function-in-end-stage-retinal-degeneration-using-subretinal-human-melanopsin-gene-therapy
#7
Samantha R De Silva, Alun R Barnard, Steven Hughes, Shu K E Tam, Chris Martin, Mandeep S Singh, Alona O Barnea-Cramer, Michelle E McClements, Matthew J During, Stuart N Peirson, Mark W Hankins, Robert E MacLaren
Optogenetic strategies to restore vision in patients who are blind from end-stage retinal degenerations aim to render remaining retinal cells light sensitive once photoreceptors are lost. Here, we assessed long-term functional outcomes following subretinal delivery of the human melanopsin gene (OPN4) in the rd1 mouse model of retinal degeneration using an adeno-associated viral vector. Ectopic expression of OPN4 using a ubiquitous promoter resulted in cellular depolarization and ganglion cell action potential firing...
October 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28972128/distinct-laterality-in-forelimb-movement-representations-of-rat-primary-and-secondary-motor-cortical-neurons-with-intratelencephalic-and-pyramidal-tract-projections
#8
Shogo Soma, Akiko Saiki, Junichi Yoshida, Alain Ríos, Masanori Kawabata, Yutaka Sakai, Yoshikazu Isomura
Two distinct motor areas, the primary and secondary motor cortices (M1 and M2), play crucial roles in voluntary movement in rodents. The aim of this study was to characterize the laterality in motor cortical representations of right and left forelimb movements. To achieve this goal, we developed a novel behavioral task, the Right-Left Pedal task, in which a head-restrained male rat manipulates a right or left pedal with the corresponding forelimb. This task enabled us to monitor independent movements of both forelimbs with high spatiotemporal resolution...
October 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28972125/sub-millisecond-optogenetic-control-of-neuronal-firing-with-two-photon-holographic-photoactivation-of-chronos
#9
E Ronzitti, R Conti, V Zampini, D Tanese, A J Foust, N Klapoetke, E S Boyden, E Papagiakoumou, V Emiliani
Optogenetic neuronal network manipulation promises to unravel a long-standing mystery in neuroscience: how does microcircuit activity causally relate to behavioral and pathological states? The challenge to evoke spikes with high spatial and temporal complexity necessitates further joint development of light-delivery approaches and custom opsins. Two-photon light-targeting strategies demonstrated, in-depth generation of action potentials in photosensitive neurons both in-vitro and in-vivo, but thus far lack the temporal precision necessary to induce precisely timed spiking events...
October 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28966085/distinct-roles-of-ventromedial-versus-ventrolateral-striatal-medium-spiny-neurons-in-reward-oriented-behavior
#10
Iku Tsutsui-Kimura, Akiyo Natsubori, Marina Mori, Kenta Kobayashi, Michael R Drew, Alban de Kerchove d'Exaerde, Masaru Mimura, Kenji F Tanaka
The ventral striatum (VS) is a key brain center regulating reward-oriented behavior [1-4]. The VS can be anatomically divided into medial (VMS) and lateral (VLS) portions based on cortical input patterns. The VMS receives inputs from medial pallium-originated limbic structures (e.g., the medial prefrontal cortex [mPFC]), and the VLS receives inputs from the lateral pallium-originated areas (e.g., the insula) [5, 6]. This anatomical feature led us to hypothesize a functional segregation within the VS in terms of the regulation of reward-oriented behavior...
October 9, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28965837/systematic-examination-of-the-impact-of-depolarization-duration-on-thalamic-reticular-nucleus-firing-in-vivo
#11
Bryan Higashikubo, Christopher I Moore
The thalamic reticular nucleus (TRN) is optimally positioned to regulate information processing and state dynamics in dorsal thalamus. Distinct inputs depolarize TRN on multiple time scales, including thalamocortical afferents, corticothalamic 'feedback', and neuromodulation. Here, we systematically tested the concurrent and after-effects of depolarization duration on TRN firing in vivo using selective optogenetic drive. In VGAT-ChR2 mice, we isolated TRN single units (SU: N = 100 neurons) that responded at brief latency (≤5 ms) to stimulation...
September 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/28948190/restoring-vision-in-mice-with-retinal-degeneration-using-multicharacteristic-opsin
#12
Weldon Wright, Sivakumar Gajjeraman, Subrata Batabyal, Sanjay Pradhan, Sulagna Bhattacharya, Vasu Mahapatra, Ashutosh Tripathy, Samarendra Mohanty
Retinal degenerative diseases, such as retinitis pigmentosa (RP) and dry age-related macular degeneration, have led to loss of vision in millions of individuals. Currently, no surgical or medical treatment is available, although optogenetic therapies are in clinical development. We demonstrate vision restoration using multicharacteristics opsin (MCO1) in animal models with degenerated retina. MCO1 is reliably delivered to specific retinal cells via intravitreal injection of adeno-associated virus (vMCO1), leading to significant improvement in visually guided behavior conducted using a radial arm water maze...
October 2017: Neurophotonics
https://www.readbyqxmd.com/read/28942046/chronic-ethanol-exposure-increases-inhibition-of-optically-targeted-phasic-dopamine-release-in-the-nucleus-accumbens-core-and-medial-shell-ex-vivo
#13
James R Melchior, Sara R Jones
Dopamine signaling encodes reward learning and motivated behavior through modulation of synaptic signaling in the nucleus accumbens, and aberrations in these processes are thought to underlie obsessive behaviors associated with alcohol abuse. The nucleus accumbens is divided into core and shell sub-regions with overlapping but also divergent contributions to behavior. Here we optogenetically targeted dopamine projections to the accumbens allowing us to isolate stimulation of dopamine terminals ex vivo. We applied 5 pulse (phasic) light stimulations to probe intrinsic differences in dopamine release parameters across regions...
September 20, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28939413/striatonigral-direct-pathway-activation-is-sufficient-to-induce-repetitive-behaviors
#14
Youcef Bouchekioua, Iku Tsutsui-Kimura, Hiromi Sano, Miwako Koizumi, Kenji F Tanaka, Keitaro Yoshida, Yutaka Kosaki, Shigeru Watanabe, Masaru Mimura
Pharmacological intervention in the substantia nigra is known to induce repetitive behaviors in rodents, but a direct causal relationship between a particular neural circuit and repetitive behavior has not yet been established. Here we demonstrate that acute excitation in dopamine D1 receptor-expressing MSNs terminals in the substantia nigra pars reticulata by optogenetics resulted in sustained and chronic repetitive behaviors. These data show for the first time that activation of the striatonigral direct pathway is sufficient to generate motor stereotypies...
September 19, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28912243/thirst-associated-preoptic-neurons-encode-an-aversive-motivational-drive
#15
William E Allen, Laura A DeNardo, Michael Z Chen, Cindy D Liu, Kyle M Loh, Lief E Fenno, Charu Ramakrishnan, Karl Deisseroth, Liqun Luo
Water deprivation produces a drive to seek and consume water. How neural activity creates this motivation remains poorly understood. We used activity-dependent genetic labeling to characterize neurons activated by water deprivation in the hypothalamic median preoptic nucleus (MnPO). Single-cell transcriptional profiling revealed that dehydration-activated MnPO neurons consist of a single excitatory cell type. After optogenetic activation of these neurons, mice drank water and performed an operant lever-pressing task for water reward with rates that scaled with stimulation frequency...
September 15, 2017: Science
https://www.readbyqxmd.com/read/28912215/the-form-and-function-of-channelrhodopsin
#16
REVIEW
Karl Deisseroth, Peter Hegemann
Channelrhodopsins are light-gated ion channels that, via regulation of flagellar function, enable single-celled motile algae to seek ambient light conditions suitable for photosynthesis and survival. These plant behavioral responses were initially investigated more than 150 years ago. Recently, major principles of function for light-gated ion channels have been elucidated by creating channelrhodopsins with kinetics that are accelerated or slowed over orders of magnitude, by discovering and designing channelrhodopsins with altered spectral properties, by solving the high-resolution channelrhodopsin crystal structure, and by structural model-guided redesign of channelrhodopsins for altered ion selectivity...
September 15, 2017: Science
https://www.readbyqxmd.com/read/28912160/dopamine-d2-receptors-modulate-pyramidal-neurons-in-mouse-medial-prefrontal-cortex-through-a-stimulatory-g-protein-pathway
#17
Sarah E Robinson, Vikaas S Sohal
Dopaminergic modulation of prefrontal cortex is believed to play key roles in many cognitive functions and to be disrupted in pathological conditions such as schizophrenia. We have previously described a phenomenon whereby dopamine D2 receptor (D2R) activation elicits afterdepolarizations (ADPs) in subcortically-projecting (SC) pyramidal neurons within L5 of the prefrontal cortex. These D2R-induced ADPs only occur following synaptic input which activates NMDA receptors (NMDARs) even when the delay between the synaptic input and afterdepolarizations is relatively long, e...
September 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28910617/whole-cell-recording-of-neuronal-membrane-potential-during-behavior
#18
REVIEW
Carl C H Petersen
Neuronal membrane potential is of fundamental importance for the mechanistic understanding of brain function. This review discusses progress in whole-cell patch-clamp recordings for low-noise measurement of neuronal membrane potential in awake behaving animals. Whole-cell recordings can be combined with two-photon microscopy to target fluorescently labeled neurons, revealing cell-type-specific membrane potential dynamics of retrogradely or genetically labeled neurons. Dual whole-cell recordings reveal behavioral modulation of membrane potential synchrony and properties of synaptic transmission in vivo...
September 13, 2017: Neuron
https://www.readbyqxmd.com/read/28898248/place-field-assembly-distribution-encodes-preferred-locations
#19
Omar Mamad, Lars Stumpp, Harold M McNamara, Charu Ramakrishnan, Karl Deisseroth, Richard B Reilly, Marian Tsanov
The hippocampus is the main locus of episodic memory formation and the neurons there encode the spatial map of the environment. Hippocampal place cells represent location, but their role in the learning of preferential location remains unclear. The hippocampus may encode locations independently from the stimuli and events that are associated with these locations. We have discovered a unique population code for the experience-dependent value of the context. The degree of reward-driven navigation preference highly correlates with the spatial distribution of the place fields recorded in the CA1 region of the hippocampus...
September 2017: PLoS Biology
https://www.readbyqxmd.com/read/28892628/no-photon-wasted-an-efficient-and-selective-singlet-oxygen-photosensitizing-protein
#20
Michael Westberg, Mikkel Bregnhøj, Michael Etzerodt, Peter R Ogilby
Optogenetics has been, and will continue to be, a boon to mechanistic studies of cellular processes. Genetically encodable proteins that sensitize the production of reactive oxygen species (ROS) are expected to play an increasingly important role, particularly in elucidating mechanisms of temporally and spatially dependent cell signaling. However, a substantial challenge in developing such photosensitizing proteins has been to funnel the optical excitation energy into the initial selective production of only one ROS...
September 27, 2017: Journal of Physical Chemistry. B
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