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Optogenetics and behavior

Jessica Tooley, Lauren Marconi, Jason Bondoc Alipio, Bridget Matikainen-Ankney, Polymnia Georgiou, Alexxai V Kravitz, Meaghan C Creed
BACKGROUND: The ability to appropriately integrate and respond to rewarding and aversive stimuli is essential for survival. The ventral pallidum (VP) plays a critical role in processing both rewarding and aversive stimuli. However, the VP is a heterogeneous structure, and how VP subpopulations integrate into larger reward networks to ultimately modulate these behaviors is not known. We identify a noncanonical population of glutamatergic VP neurons that play a unique role in responding to aversive stimuli and constraining inappropriate reward seeking...
January 12, 2018: Biological Psychiatry
Anh D Bui, Theresa M Nguyen, Charles Limouse, Hannah K Kim, Gergely G Szabo, Sylwia Felong, Mattia Maroso, Ivan Soltesz
Temporal lobe epilepsy (TLE) is characterized by debilitating, recurring seizures and an increased risk for cognitive deficits. Mossy cells (MCs) are key neurons in the hippocampal excitatory circuit, and the partial loss of MCs is a major hallmark of TLE. We investigated how MCs contribute to spontaneous ictal activity and to spatial contextual memory in a mouse model of TLE with hippocampal sclerosis, using a combination of optogenetic, electrophysiological, and behavioral approaches. In chronically epileptic mice, real-time optogenetic modulation of MCs during spontaneous hippocampal seizures controlled the progression of activity from an electrographic to convulsive seizure...
February 16, 2018: Science
Michał Kiełbus, Jakub Czapiński, Adrian Odrzywolski, Grażyna Stasiak, Kamila Szymańska, Joanna Kałafut, Michał Kos, Krzysztof Giannopoulos, Andrzej Stepulak, Adolfo Rivero-Müller
The discovery and domestication of biomolecules that respond to light has taken a light of its own, providing new molecular tools with incredible spatio-temporal resolution to manipulate cellular behavior. Areas covered: The authors herein analyze the current optogenetic tools in light of their current, and potential, uses in cancer drug discovery, biosafety and cancer biology. Expert opinion: The pipeline from drug discovery to the clinic is plagued with drawbacks, where most drugs fail in either efficacy or safety...
February 15, 2018: Expert Opinion on Drug Discovery
Tengfei Ma, Yifeng Cheng, Emily Roltsch Hellard, Xuehua Wang, Jiayi Lu, Xinsheng Gao, Cathy C Y Huang, Xiao-Yan Wei, Jun-Yuan Ji, Jun Wang
Addiction is proposed to arise from alterations in synaptic strength via mechanisms of long-term potentiation (LTP) and depression (LTD). However, the causality between these synaptic processes and addictive behaviors is difficult to demonstrate. Here we report that LTP and LTD induction altered operant alcohol self-administration, a motivated drug-seeking behavior. We first induced LTP by pairing presynaptic glutamatergic stimulation with optogenetic postsynaptic depolarization in the dorsomedial striatum, a brain region known to control goal-directed behavior...
February 12, 2018: Nature Neuroscience
Krista L Wahlstrom, Mary L Huff, Eric B Emmons, John H Freeman, Nandakumar S Narayanan, Christa K McIntyre, Ryan T LaLumiere
Although evidence suggests that the basolateral amygdala (BLA) and dorsal hippocampus (DH) work together to influence the consolidation of spatial/contextual learning, the circuit mechanism by which the BLA selectively modulates spatial/contextual memory consolidation is not clear. The medial entorhinal cortex (mEC) is a critical region in the hippocampus-based system for processing spatial information. As an efferent target of the BLA, the mEC is a candidate by which the BLA influences the consolidation of such learning...
February 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Scott F Owen, Joshua D Berke, Anatol C Kreitzer
Fast-spiking interneurons (FSIs) are a prominent class of forebrain GABAergic cells implicated in two seemingly independent network functions: gain control and network plasticity. Little is known, however, about how these roles interact. Here, we use a combination of cell-type-specific ablation, optogenetics, electrophysiology, imaging, and behavior to describe a unified mechanism by which striatal FSIs control burst firing, calcium influx, and synaptic plasticity in neighboring medium spiny projection neurons (MSNs)...
February 8, 2018: Cell
Joanna Urban-Ciecko, Jean-Sebastien Jouhanneau, Stephanie E Myal, James F A Poulet, Alison L Barth
Sleep, waking, locomotion, and attention are associated with cell-type-specific changes in neocortical activity. The effect of brain state on circuit output requires understanding of how neuromodulators influence specific neuronal classes and their synapses, with normal patterns of neuromodulator release from endogenous sources. We investigated the state-dependent modulation of a ubiquitous feedforward inhibitory motif in mouse sensory cortex, local pyramidal (Pyr) inputs onto somatostatin (SST)-expressing interneurons...
February 7, 2018: Neuron
L Rudmann, M T Alt, D Ashouri Vajari, T Stieglitz
Optogenetics opened not only new exciting opportunities to interrogate the nervous system but also requires adequate probes to facilitate these wishes. Therefore, a multidisciplinary effort is essential to match these technical opportunities with biological needs in order to establish a stable and functional material-tissue interface. This in turn can address an optical intervention of the genetically modified, light sensitive cells in the nervous system and recording of electrical signals from single cells and neuronal networks that result in behavioral changes...
February 4, 2018: Current Opinion in Neurobiology
Thitaphat Ngernsutivorakul, Thomas S White, Robert T Kennedy
Probe techniques for monitoring in vivo chemistry (e.g., electrochemical sensors and microdialysis sampling probes) have significantly contributed to a better understanding of neurotransmission in correlation to behaviors and neurological disorders. Microfabrication allows construction of neural probes with high reproducibility, scalability, design flexibility, and multiplexed features. This technology has translated well into fabricating miniaturized neurochemical probes for electrochemical detection and sampling...
February 5, 2018: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Claire Gizowski, Cristian Zaelzer, Charles W Bourque
Previous studies have shown that mice housed under 12:12 h light-dark conditions display a pronounced increase in water intake during a 2-hour anticipatory period (AP) near the end of their active period (Zeitgeber Time ZT; ZT21.5-ZT23.5) compared to the preceding basal period (BP, ZT19.5-ZT21.5). This increased water intake during the AP is not associated with physiological stimuli for thirst, such as food intake, hyperosmolality, hyperthermia, or hypovolemia. Denying mice the water intake supplement during the AP causes them to be dehydrated at wake time...
February 5, 2018: Journal of Neuroendocrinology
Yi Li, Jiawei Zeng, Juen Zhang, Chenyu Yue, Weixin Zhong, Zhixiang Liu, Qiru Feng, Minmin Luo
The interactions between predator and prey represent some of the most dramatic events in nature and constitute a matter of life and death for both sides. The hypothalamus has been implicated in driving predation and evasion; however, the exact hypothalamic neural circuits underlying these behaviors remain poorly defined. Here, we demonstrate that inhibitory and excitatory projections from the mouse lateral hypothalamus (LH) to the periaqueductal gray (PAG) in the midbrain drive, respectively, predation and evasion...
January 29, 2018: Neuron
Robert R Rozeske, Daniel Jercog, Nikolaos Karalis, Fabrice Chaudun, Suzana Khoder, Delphine Girard, Nânci Winke, Cyril Herry
Survival critically depends on selecting appropriate defensive or exploratory behaviors and is strongly influenced by the surrounding environment. Contextual discrimination is a fundamental process that is thought to depend on the prefrontal cortex to integrate sensory information from the environment and regulate adaptive responses to threat during uncertainty. However, the precise prefrontal circuits necessary for discriminating a previously threatening context from a neutral context remain unknown. Using a combination of single-unit recordings and optogenetic manipulations, we identified a neuronal subpopulation in the dorsal medial prefrontal cortex (dmPFC) that projects to the lateral and ventrolateral periaqueductal gray (l/vlPAG) and is selectively activated during contextual fear discrimination...
January 24, 2018: Neuron
Jessica C Jimenez, Katy Su, Alexander R Goldberg, Victor M Luna, Jeremy S Biane, Gokhan Ordek, Pengcheng Zhou, Samantha K Ong, Matthew A Wright, Larry Zweifel, Liam Paninski, René Hen, Mazen A Kheirbek
The hippocampus is traditionally thought to transmit contextual information to limbic structures where it acquires valence. Using freely moving calcium imaging and optogenetics, we show that while the dorsal CA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA)...
January 30, 2018: Neuron
Amelie Bergs, Christian Schultheis, Elisabeth Fischer, Satoshi P Tsunoda, Karen Erbguth, Steven J Husson, Elena Govorunova, John L Spudich, Georg Nagel, Alexander Gottschalk, Jana F Liewald
In optogenetics, rhodopsins were established as light-driven tools to manipulate neuronal activity. However, during long-term photostimulation using channelrhodopsin (ChR), desensitization can reduce effects. Furthermore, requirement for continuous presence of the chromophore all-trans retinal (ATR) in model systems lacking sufficient endogenous concentrations limits its applicability. We tested known, and engineered and characterized new variants of de- and hyperpolarizing rhodopsins in Caenorhabditis elegans...
2018: PloS One
Marta Díaz-Quesada, Isaac A Youngstrom, Yusuke Tsuno, Kyle R Hansen, Michael N Economo, Matt Wachowiak
In mammals olfactory sensation depends on inhalation, which controls activation of sensory neurons and temporal patterning of central activity. Odor representations by mitral and tufted (MT) cells, the main output from the olfactory bulb (OB), reflect sensory input as well as excitation and inhibition from OB circuits, which may change as sniff frequency increases. To test the impact of sampling frequency on MT cell odor responses, we obtained whole-cell recordings from MT cells in anesthetized male and female mice while varying inhalation frequency via tracheotomy, allowing comparison of inhalation-linked responses across cells...
January 26, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Edison Chen, Valeria Lallai, Yasmine Sherafat, Nickolas P Grimes, Anna N Pushkin, J P Fowler, Christie D Fowler
The recent development of transgenic rodent lines expressing cre recombinase in a cell-specific manner, along with advances in engineered viral vectors, has permitted in-depth investigations into circuit function. However, emerging evidence has begun to suggest that genetic modifications may introduce unexpected caveats. In the current studies, we sought to extensively characterize male and female mice from both the ChAT(BAC)-Cre mouse line, created with the bacterial artificial chromosome (BAC) method, and ChAT(IRES)-Cre mouse line, generated with the internal ribosome entry site (IRES) method...
January 25, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Hanen Khabou, Marcela Garita-Hernandez, Antoine Chaffiol, Sacha Reichman, Céline Jaillard, Elena Brazhnikova, Stéphane Bertin, Valérie Forster, Mélissa Desrosiers, Céline Winckler, Olivier Goureau, Serge Picaud, Jens Duebel, José-Alain Sahel, Deniz Dalkara
Intraocular injection of adeno-associated viral (AAV) vectors has been an evident route for delivering gene drugs into the retina. However, gaps in our understanding of AAV transduction patterns within the anatomically unique environments of the subretinal and intravitreal space of the primate eye impeded the establishment of noninvasive and efficient gene delivery to foveal cones in the clinic. Here, we establish new vector-promoter combinations to overcome the limitations associated with AAV-mediated cone transduction in the fovea with supporting studies in mouse models, human induced pluripotent stem cell-derived organoids, postmortem human retinal explants, and living macaques...
January 25, 2018: JCI Insight
John J Briguglio, Mark Aizenberg, Vijay Balasubramanian, Maria N Geffen
Excitatory and inhibitory neurons in the mammalian sensory cortex form interconnected circuits that control cortical stimulus selectivity and sensory acuity. Theoretical studies have predicted that suppression of inhibition in such excitatory-inhibitory networks can lead to either an increase or, paradoxically, a decrease in excitatory neuronal firing, with consequent effects on stimulus selectivity. We tested whether modulation of inhibition or excitation in the auditory cortex of male mice could evoke such a variety of effects in tone-evoked responses and in behavioral frequency discrimination acuity...
January 24, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Pedro A Sánchez-Murcia, Juan José Nogueira, Leticia Gonzalez
The characterization of electronic properties of metal complexes embedded in membrane environments is of paramount importance to develop efficient photosensitizers in optogenetic applications. Molecular dynamics and QM/MM simulations together with quantitative wavefunction analysis reveal a directional electronic redistribution of the exciton formed upon excitation of [Ru(bpy)2(bpy-C17)]2+ when going from water to a lipid bilayer, despite the media neither influences the metal-to-ligand charge-transfer character nor the excitation energy of the absorption spectra...
January 24, 2018: Journal of Physical Chemistry Letters
Anthony D Fouad, Shelly Teng, Julian R Mark, Alice Liu, Pilar Alvarez-Illera, Hongfei Ji, Angelica Du, Priya D Bhirgoo, Eli Cornblath, Sihui Asuka Guan, Christopher Fang-Yen
Coordinated rhythmic movements are ubiquitous in animal behavior. In many organisms, chains of neural oscillators underlie the generation of these rhythms. In C. elegans, locomotor wave generation has been poorly understood; in particular, it is unclear where in the circuit rhythms are generated, and whether there exists more than one such generator. We used optogenetic and ablation experiments to probe the nature of rhythm generation in the locomotor circuit. We found that multiple sections of forward locomotor circuitry are capable of independently generating rhythms...
January 23, 2018: ELife
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