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Derek Garden, Arianna Rinaldi, Matthew F Nolan
The inferior olive plays a critical role in motor coordination and learning by integrating diverse afferent signals to generate climbing fibre inputs to the cerebellar cortex. While it is well established that climbing fibre signals are important for motor coordination, the mechanisms by which neurones in the inferior olive integrate synaptic inputs and the roles of particular ion channels are unclear. Here, we test the hypothesis that neurones in the inferior olive actively integrate glutamatergic synaptic inputs...
October 21, 2016: Journal of Physiology
Kenneth M McCullough, Dennis Choi, Jidong Guo, Kelsey Zimmerman, Jordan Walton, Donald G Rainnie, Kerry J Ressler
Molecular characterization of neuron populations, particularly those controlling threat responses, is essential for understanding the cellular basis of behaviour and identifying pharmacological agents acting selectively on fear-controlling circuitry. Here we demonstrate a comprehensive workflow for identification of pharmacologically tractable markers of behaviourally characterized cell populations. Thy1-eNpHR-, Thy1-Cre- and Thy1-eYFP-labelled neurons of the BLA consistently act as fear inhibiting or 'Fear-Off' neurons during behaviour...
October 21, 2016: Nature Communications
Gaigai Yu, Hiroyuki Onodera, Yuki Aono, Fuun Kawano, Yoshibumi Ueda, Akihiro Furuya, Hideyuki Suzuki, Moritoshi Sato
Alpha subunits of heterotrimeric G proteins (Gα) are involved in a variety of cellular functions. Here we report an optogenetic strategy to spatially and temporally manipulate Gα in living cells. More specifically, we applied the blue light-induced dimerization system, known as the Magnet system, and an alternative red light-induced dimerization system consisting of Arabidopsis thaliana phytochrome B (PhyB) and phytochrome-interacting factor 6 (PIF6) to optically control the activation of two different classes of Gα (Gαq and Gαs)...
October 21, 2016: Scientific Reports
Fan Lin, Liang Dong, Weiming Wang, Yuchen Liu, Weiren Huang, Zhiming Cai
Optogenetic gene expression systems enable spatial-temporal modulation of gene transcription and cell behavior. Although applications in biomedicine are emerging, the utility of optogenetic gene switches remains elusive in cancer research due to the relative low gene activation efficiency. Here, we present an optimized CRISPR-Cas9-based light-inducible gene expression device that controls gene transcription in a dose-dependent manner. To prove the potential utility of this device, P53 was tested as a functional target in the bladder cancer cell models...
2016: International Journal of Biological Sciences
Thomas Viereckel, Sylvie Dumas, Casey J A Smith-Anttila, Bianca Vlcek, Zisis Bimpisidis, Malin C Lagerström, Åsa Konradsson-Geuken, Åsa Wallén-Mackenzie
The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) of the midbrain are associated with Parkinson's disease (PD), schizophrenia, mood disorders and addiction. Based on the recently unraveled heterogeneity within the VTA and SNc, where glutamate, GABA and co-releasing neurons have been found to co-exist with the classical dopamine neurons, there is a compelling need for identification of gene expression patterns that represent this heterogeneity and that are of value for development of human therapies...
October 20, 2016: Scientific Reports
David S Freedman, Joseph B Schroeder, Gregory I Telian, Zhengyang Zhang, Smrithi Sunil, Jason T Ritt
OBJECTIVE: Behavioral neuroscience studies in freely moving rodents require small, light-weight implants to facilitate neural recording and stimulation. Our goal was to develop an integrated package of 3D printed parts and assembly aids for labs to rapidly fabricate, with minimal training, an implant that combines individually positionable microelectrodes, an optical fiber, zero insertion force (ZIF-clip) headstage connection, and secondary recording electrodes, e.g. for electromyography (EMG)...
October 20, 2016: Journal of Neural Engineering
Clarissa J Whitmire, Daniel C Millard, Garrett B Stanley
Sensory stimulation drives complex interactions across neural circuits as information is encoded and then transmitted from one brain region to the next. In the highly interconnected thalamocortical circuit, these complex interactions elicit repeatable neural dynamics in response to temporal patterns of stimuli that provide insight into the circuit properties that generated them. Here, using a combination of in-vivo voltage sensitive dye (VSD) imaging of cortex, single unit recording in thalamus, and optogenetics to manipulate thalamic state in the rodent vibrissa pathway, we probed the thalamocortical circuit with simple temporal patterns of stimuli delivered either to the whiskers on the face (sensory stimulation) or to the thalamus directly via electrical or optogenetic inputs (artificial stimulation)...
October 19, 2016: Journal of Neurophysiology
Verónica Pérez-Schuster, Anirudh Kulkarni, Morgane Nouvian, Sebastián A Romano, Konstantinos Lygdas, Adrien Jouary, Mario Dippopa, Thomas Pietri, Mathieu Haudrechy, Virginie Candat, Jonathan Boulanger-Weill, Vincent Hakim, Germán Sumbre
Following moving visual stimuli (conditioning stimuli, CS), many organisms perceive, in the absence of physical stimuli, illusory motion in the opposite direction. This phenomenon is known as the motion aftereffect (MAE). Here, we use MAE as a tool to study the neuronal basis of visual motion perception in zebrafish larvae. Using zebrafish eye movements as an indicator of visual motion perception, we find that larvae perceive MAE. Blocking eye movements using optogenetics during CS presentation did not affect MAE, but tectal ablation significantly weakened it...
October 18, 2016: Cell Reports
Krisztián A Kovács, Joseph O'Neill, Philipp Schoenenberger, Markku Penttonen, Damaris K Ranguel Guerrero, Jozsef Csicsvari
During hippocampal sharp wave/ripple (SWR) events, previously occurring, sensory input-driven neuronal firing patterns are replayed. Such replay is thought to be important for plasticity-related processes and consolidation of memory traces. It has previously been shown that the electrical stimulation-induced disruption of SWR events interferes with learning in rodents in different experimental paradigms. On the other hand, the cognitive map theory posits that the plastic changes of the firing of hippocampal place cells constitute the electrophysiological counterpart of the spatial learning, observable at the behavioral level...
2016: PloS One
Hideyuki Matsumoto, Ju Tian, Naoshige Uchida, Mitsuko Watabe-Uchida
Dopamine is thought to regulate learning from appetitive and aversive events. Here we examined how optogenetically-identified dopamine neurons in the lateral ventral tegmental area of mice respond to aversive events in different conditions. In low reward contexts, most dopamine neurons were exclusively inhibited by aversive events, and expectation reduced dopamine neurons' responses to reward and punishment. When a single odor predicted both reward and punishment, dopamine neurons' responses to that odor reflected the integrated value of both outcomes...
October 19, 2016: ELife
Ruben Machado, Nima Soltani, Suzie Dufour, Muhammad Tariqus Salam, Peter L Carlen, Roman Genov, Michael Thompson
Extracellular potassium concentration, [K⁺]o, plays a fundamental role in the physiological functions of the brain. Studies investigating changes in [K⁺]o have predominantly relied upon glass capillary electrodes with K⁺-sensitive solution gradients for their measurements. However, such electrodes are unsuitable for taking spatio-temporal measurements and are limited by the surface area of their tips. We illustrate seizures invoked chemically and in optogenetically modified mice using blue light exposure while impedimetrically measuring the response...
October 13, 2016: Biosensors
Jérémie Barral, Alex D Reyes
The balance between excitation and inhibition (E-I balance) is maintained across brain regions though the network size, strength and number of synaptic connections, and connection architecture may vary substantially. We use a culture preparation to examine the homeostatic synaptic scaling rules that produce E-I balance and in vivo-like activity. We show that synaptic strength scales with the number of connections K as ∼ , close to the ideal theoretical value. Using optogenetic techniques, we delivered spatiotemporally patterned stimuli to neurons and confirmed key theoretical predictions: E-I balance is maintained, active decorrelation occurs and the spiking correlation increases with firing rate...
October 17, 2016: Nature Neuroscience
Jianing Yu, Diego A Gutnisky, S Andrew Hires, Karel Svoboda
We rely on movement to explore the environment, for example, by palpating an object. In somatosensory cortex, activity related to movement of digits or whiskers is suppressed, which could facilitate detection of touch. Movement-related suppression is generally assumed to involve corollary discharges. Here we uncovered a thalamocortical mechanism in which cortical fast-spiking interneurons, driven by sensory input, suppress movement-related activity in layer 4 (L4) excitatory neurons. In mice locating objects with their whiskers, neurons in the ventral posteromedial nucleus (VPM) fired in response to touch and whisker movement...
October 17, 2016: Nature Neuroscience
Claudia Crocini, Cecilia Ferrantini, Raffaele Coppini, Marina Scardigli, Ping Yan, Leslie M Loew, Godfrey Smith, Elisabetta Cerbai, Corrado Poggesi, Francesco S Pavone, Leonardo Sacconi
Current rescue therapies for life-threatening arrhythmias ignore the pathological electro-anatomical substrate and base their efficacy on a generalized electrical discharge. Here, we developed an all-optical platform to examine less invasive defibrillation strategies. An ultrafast wide-field macroscope was developed to optically map action potential propagation with a red-shifted voltage sensitive dye in whole mouse hearts. The macroscope was implemented with a random-access scanning head capable of drawing arbitrarily-chosen stimulation patterns with sub-millisecond temporal resolution allowing precise epicardial activation of Channelrhodopsin2 (ChR2)...
October 17, 2016: Scientific Reports
Iryna Yavorska, Michael Wehr
Cortical inhibitory neurons exhibit remarkable diversity in their morphology, connectivity, and synaptic properties. Here, we review the function of somatostatin-expressing (SOM) inhibitory interneurons, focusing largely on sensory cortex. SOM neurons also comprise a number of subpopulations that can be distinguished by their morphology, input and output connectivity, laminar location, firing properties, and expression of molecular markers. Several of these classes of SOM neurons show unique dynamics and characteristics, such as facilitating synapses, specific axonal projections, intralaminar input, and top-down modulation, which suggest possible computational roles...
2016: Frontiers in Neural Circuits
Dohoung Kim, Huijeong Jeong, Juhyeong Lee, Jeong-Wook Ghim, Eun Sil Her, Seung-Hee Lee, Min Whan Jung
Inhibitory interneurons are thought to play crucial roles in diverse brain functions. However, roles of different inhibitory interneuron subtypes in working memory remain unclear. We found distinct activity patterns and stimulation effects of two major interneuron subtypes, parvalbumin (PV)- and somatostatin (SOM)-expressing interneurons, in the medial prefrontal cortex of mice performing a spatial working memory task. PV interneurons showed weak target-dependent delay-period activity and were strongly inhibited by reward...
October 12, 2016: Neuron
Stephan Steidl, Huiling Wang, Marco Ordonez, Shiliang Zhang, Marisela Morales
Converging evidence shows that ventral tegmental area (VTA) dopamine neurons receive laterodorsal tegmental nucleus (LDTg) cholinergic and glutamatergic inputs. To test the behavioral consequences of selectively driving the two sources of excitatory LDTg input to the VTA, channelrhodopsin-2 (ChR2) was expressed in LDTg cholinergic neurons of ChAT::Cre mice (ChAT-ChR2 mice) or in LDTg glutamatergic neurons of VGluT2::Cre mice (VGluT2-ChR2 mice). Mice were tested in a 3-chamber place preference apparatus where entry into a light-paired chamber resulted in VTA light stimulation of LDTg-cholinergic or LDTg-glutamatergic axons for the duration of a chamber stay...
October 14, 2016: European Journal of Neuroscience
Dong-Wook Park, Sarah K Brodnick, Jared P Ness, Farid Atry, Lisa Krugner-Higby, Amelia Sandberg, Solomon Mikael, Thomas J Richner, Joseph Novello, Hyungsoo Kim, Dong-Hyun Baek, Jihye Bong, Seth T Frye, Sanitta Thongpang, Kyle I Swanson, Wendell Lake, Ramin Pashaie, Justin C Williams, Zhenqiang Ma
Transparent graphene-based neural electrode arrays provide unique opportunities for simultaneous investigation of electrophysiology, various neural imaging modalities, and optogenetics. Graphene electrodes have previously demonstrated greater broad-wavelength transmittance (∼90%) than other transparent materials such as indium tin oxide (∼80%) and ultrathin metals (∼60%). This protocol describes how to fabricate and implant a graphene-based microelectrocorticography (μECoG) electrode array and subsequently use this alongside electrophysiology, fluorescence microscopy, optical coherence tomography (OCT), and optogenetics...
November 2016: Nature Protocols
Vittorio Caggiano, Vincent C K Cheung, Emilio Bizzi
Motor modules are neural entities hypothesized to be building blocks of movement construction. How motor modules are underpinned by neural circuits has remained obscured. As a first step towards dissecting these circuits, we optogenetically evoked motor outputs from the lumbosacral spinal cord of two strains of transgenic mice - the Chat, with channelrhodopsin (ChR2) expressed in motoneurons, and the Thy1, expressed in putatively excitatory neurons. Motor output was represented as a spatial field of isometric ankle force...
October 13, 2016: Scientific Reports
Vikaas S Sohal
γ oscillations, which can be identified by rhythmic electrical signals ∼30-100 Hz, consist of interactions between excitatory and inhibitory neurons that result in rhythmic inhibition capable of entraining firing within local cortical circuits. Many possible mechanisms have been described through which γ oscillations could act on cortical circuits to modulate their responses to input, alter their patterns of activity, and/or enhance the efficacy of their outputs onto downstream targets. Recently, several studies have observed changes in behavior after optogenetically manipulating neocortical γ oscillations...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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