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Brian J Duistermars, Barret D Pfeiffer, Eric D Hoopfer, David J Anderson
Threat displays are a universal feature of agonistic interactions. Whether threats are part of a continuum of aggressive behaviors or separately controlled remains unclear. We analyze threats in Drosophila and show they are triggered by male cues and visual motion, and comprised of multiple motor elements that can be flexibly combined. We isolate a cluster of ∼3 neurons whose activity is necessary for threat displays but not for other aggressive behaviors, and whose artificial activation suffices to evoke naturalistic threats in solitary flies, suggesting that the neural control of threats is modular with respect to other aggressive behaviors...
November 6, 2018: Neuron
Benjamin U Hoffman, Yoshichika Baba, Theanne N Griffith, Eugene V Mosharov, Seung-Hyun Woo, Daniel D Roybal, Gerard Karsenty, Ardem Patapoutian, David Sulzer, Ellen A Lumpkin
Epithelial-neuronal signaling is essential for sensory encoding in touch, itch, and nociception; however, little is known about the release mechanisms and neurotransmitter receptors through which skin cells govern neuronal excitability. Merkel cells are mechanosensory epidermal cells that have long been proposed to activate neuronal afferents through chemical synaptic transmission. We employed a set of classical criteria for chemical neurotransmission as a framework to test this hypothesis. RNA sequencing of adult mouse Merkel cells demonstrated that they express presynaptic molecules and biosynthetic machinery for adrenergic transmission...
November 6, 2018: Neuron
Mean-Hwan Kim, Petr Znamenskiy, Maria Florencia Iacaruso, Thomas D Mrsic-Flogel
The rules by which neurons in neocortex choose their synaptic partners are not fully understood. In sensory cortex, intermingled neurons encode different attributes of sensory inputs and relay them to different long-range targets. While neurons with similar responses to sensory stimuli make connections preferentially, the relationship between synaptic connectivity within an area and long-range projection target remains unclear. We examined the local connectivity and visual responses of primary visual cortex neurons projecting to anterolateral (AL) and posteromedial (PM) higher visual areas in mice...
November 5, 2018: Neuron
Alexandra Litvinchuk, Ying-Wooi Wan, Dan B Swartzlander, Fading Chen, Allysa Cole, Nicholas E Propson, Qian Wang, Bin Zhang, Zhandong Liu, Hui Zheng
Strong evidence implicates the complement pathway as an important contributor to amyloid pathology in Alzheimer's disease (AD); however, the role of complement in tau modulation remains unclear. Here we show that the expression of C3 and C3a receptor (C3aR1) are positively correlated with cognitive decline and Braak staging in human AD brains. Deletion of C3ar1 in PS19 mice results in the rescue of tau pathology and attenuation of neuroinflammation, synaptic deficits, and neurodegeneration. Through RNA sequencing and cell-type-specific transcriptomic analysis, we identify a C3aR-dependent transcription factor network that regulates a reactive glial switch whose inactivation ameliorates disease-associated microglia and neurotoxic astrocyte signatures...
November 3, 2018: Neuron
Matthew S Creamer, Omer Mano, Damon A Clark
An animal's self-motion generates optic flow across its retina, and it can use this visual signal to regulate its orientation and speed through the world. While orientation control has been studied extensively in Drosophila and other insects, much less is known about the visual cues and circuits that regulate translational speed. Here, we show that flies regulate walking speed with an algorithm that is tuned to the speed of visual motion, causing them to slow when visual objects are nearby. This regulation does not depend strongly on the spatial structure or the direction of visual stimuli, making it algorithmically distinct from the classic computation that controls orientation...
November 2, 2018: Neuron
Takaya Ogasawara, Masafumi Nejime, Masahiko Takada, Masayuki Matsumoto
Animals need to inhibit inappropriate actions that would lead to unwanted outcomes. Although this ability, called response inhibition, is impaired in neurological/psychiatric disorders with dopaminergic dysfunctions, how dopamine regulates response inhibition remains unclear. Here we investigated neuronal signals of the nigrostriatal dopamine system in monkeys performing a saccadic countermanding task. Subsets of dopamine neurons in the substantia nigra and striatal neurons receiving the dopaminergic input were activated when the monkey was required to cancel a planned saccadic eye movement...
November 1, 2018: Neuron
Mateusz C Ambrozkiewicz, Manuela Schwark, Mika Kishimoto-Suga, Ekaterina Borisova, Kei Hori, Andrea Salazar-Lázaro, Alexandra Rusanova, Bekir Altas, Lars Piepkorn, Paraskevi Bessa, Theres Schaub, Xin Zhang, Tamara Rabe, Silvia Ripamonti, Marta Rosário, Haruhiko Akiyama, Olaf Jahn, Tatsuya Kobayashi, Mikio Hoshino, Victor Tarabykin, Hiroshi Kawabe
The establishment of axon-dendrite polarity is fundamental for radial migration of neurons during cortex development of mammals. We demonstrate that the E3 ubiquitin ligases WW-Containing Proteins 1 and 2 (Wwp1 and Wwp2) are indispensable for proper polarization of developing neurons. We show that knockout of Wwp1 and Wwp2 results in defects in axon-dendrite polarity in pyramidal neurons, and their aberrant laminar cortical distribution. Knockout of miR-140, encoded in Wwp2 intron, engenders phenotypic changes analogous to those upon Wwp1 and Wwp2 deletion...
October 30, 2018: Neuron
Thomas O Helmbrecht, Marco Dal Maschio, Joseph C Donovan, Styliani Koutsouli, Herwig Baier
The brain converts perceptual information into appropriate patterns of muscle activity depending on the categorization and localization of sensory cues. Sensorimotor information might either be encoded by distributed networks or by "labeled lines" connecting sensory channels to dedicated behavioral pathways. Here we investigate, in the context of natural behavior, how the tectum of larval zebrafish can inform downstream premotor areas. Optogenetic mapping revealed a tectal motor map underlying locomotor maneuvers for escape and approach...
October 30, 2018: Neuron
Brian E Kalmbach, Anatoly Buchin, Brian Long, Jennie Close, Anirban Nandi, Jeremy A Miller, Trygve E Bakken, Rebecca D Hodge, Peter Chong, Rebecca de Frates, Kael Dai, Zoe Maltzer, Philip R Nicovich, C Dirk Keene, Daniel L Silbergeld, Ryder P Gwinn, Charles Cobbs, Andrew L Ko, Jeffrey G Ojemann, Christof Koch, Costas A Anastassiou, Ed S Lein, Jonathan T Ting
Gene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single-cell/nucleus RNA sequencing revealed ubiquitous HCN1-subunit expression in excitatory neurons in human, but not mouse, supragranular layers. Using patch-clamp recordings, we found stronger h-channel-related membrane properties in supragranular pyramidal neurons in human temporal cortex, compared to mouse supragranular pyramidal neurons in temporal association area...
October 30, 2018: Neuron
Borislav Dejanovic, Melanie A Huntley, Ann De Mazière, William J Meilandt, Tiffany Wu, Karpagam Srinivasan, Zhiyu Jiang, Vineela Gandham, Brad A Friedman, Hai Ngu, Oded Foreman, Richard A D Carano, Ben Chih, Judith Klumperman, Corey Bakalarski, Jesse E Hanson, Morgan Sheng
Synapse loss and Tau pathology are hallmarks of Alzheimer's disease (AD) and other tauopathies, but how Tau pathology causes synapse loss is unclear. We used unbiased proteomic analysis of postsynaptic densities (PSDs) in Tau-P301S transgenic mice to identify Tau-dependent alterations in synapses prior to overt neurodegeneration. Multiple proteins and pathways were altered in Tau-P301S PSDs, including depletion of a set of GTPase-regulatory proteins that leads to actin cytoskeletal defects and loss of dendritic spines...
October 30, 2018: Neuron
Giacomo Benvenuti, Yuzhi Chen, Charu Ramakrishnan, Karl Deisseroth, Wilson S Geisler, Eyal Seidemann
Humans have remarkable scale-invariant visual capabilities. For example, our orientation discrimination sensitivity is largely constant over more than two orders of magnitude of variations in stimulus spatial frequency (SF). Orientation-selective V1 neurons are likely to contribute to orientation discrimination. However, because at any V1 location neurons have a limited range of receptive field (RF) sizes, we predict that at low SFs V1 neurons will carry little orientation information. If this were the case, what could account for the high behavioral sensitivity at low SFs? Using optical imaging in behaving macaques, we show that, as predicted, V1 orientation-tuned responses drop rapidly with decreasing SF...
October 30, 2018: Neuron
Alexandra Oranth, Christian Schultheis, Oleg Tolstenkov, Karen Erbguth, Jatin Nagpal, David Hain, Martin Brauner, Sebastian Wabnig, Wagner Steuer Costa, Rebecca D McWhirter, Sven Zels, Sierra Palumbos, David M Miller Iii, Isabel Beets, Alexander Gottschalk
Finding food and remaining at a food source are crucial survival strategies. We show how neural circuits and signaling molecules regulate these food-related behaviors in Caenorhabditis elegans. In the absence of food, AVK interneurons release FLP-1 neuropeptides that inhibit motorneurons to regulate body posture and velocity, thereby promoting dispersal. Conversely, AVK photoinhibition promoted dwelling behavior. We identified FLP-1 receptors required for these effects in distinct motoneurons. The DVA interneuron antagonizes signaling from AVK by releasing cholecystokinin-like neuropeptides that potentiate cholinergic neurons, in response to dopaminergic neurons that sense food...
October 29, 2018: Neuron
Francesca Cargnin, Ji-Sun Kwon, Sol Katzman, Bin Chen, Jae W Lee, Soo-Kyung Lee
The hallmarks of FOXG1 syndrome, which results from mutations in a single FOXG1 allele, include cortical atrophy and corpus callosum agenesis. However, the etiology for these structural deficits and the role of FOXG1 in cortical projection neurons remain unclear. Here we demonstrate that Foxg1 in pyramidal neurons plays essential roles in establishing cortical layers and the identity and axon trajectory of callosal projection neurons. The neuron-specific actions of Foxg1 are achieved by forming a transcription complex with Rp58...
October 26, 2018: Neuron
Alexandre Tiriac, Benjamin E Smith, Marla B Feller
Retinal waves are bursts of correlated activity that occur prior to eye opening and provide a critical source of activity that drives the refinement of retinofugal projections. Retinal waves are thought to be initiated spontaneously with their spatiotemporal features dictated by immature neural circuits. Here we demonstrate that, during the second postnatal week in mice, changes in light intensity dictate where and when a subset of retinal waves are triggered via activation of conventional photoreceptors. Propagation properties of triggered waves are indistinguishable from spontaneous waves, indicating that they are activating the same retinal circuits...
October 22, 2018: Neuron
Jone López-Erauskin, Takahiro Tadokoro, Michael W Baughn, Brian Myers, Melissa McAlonis-Downes, Carlos Chillon-Marinas, Joshua N Asiaban, Jonathan Artates, Anh T Bui, Anne P Vetto, Sandra K Lee, Ai Vy Le, Ying Sun, Mélanie Jambeau, Jihane Boubaker, Deborah Swing, Jinsong Qiu, Geoffrey G Hicks, Zhengyu Ouyang, Xiang-Dong Fu, Lino Tessarollo, Shuo-Chien Ling, Philippe A Parone, Christopher E Shaw, Martin Marsala, Clotilde Lagier-Tourenne, Don W Cleveland, Sandrine Da Cruz
Through the generation of humanized FUS mice expressing full-length human FUS, we identify that when expressed at near endogenous murine FUS levels, both wild-type and ALS-causing and frontotemporal dementia (FTD)-causing mutations complement the essential function(s) of murine FUS. Replacement of murine FUS with mutant, but not wild-type, human FUS causes stress-mediated induction of chaperones, decreased expression of ion channels and transporters essential for synaptic function, and reduced synaptic activity without loss of nuclear FUS or its cytoplasmic aggregation...
October 17, 2018: Neuron
Matthew G Perich, Juan A Gallego, Lee E Miller
Long-term learning of language, mathematics, and motor skills likely requires cortical plasticity, but behavior often requires much faster changes, sometimes even after single errors. Here, we propose one neural mechanism to rapidly develop new motor output without altering the functional connectivity within or between cortical areas. We tested cortico-cortical models relating the activity of hundreds of neurons in the premotor (PMd) and primary motor (M1) cortices throughout adaptation to reaching movement perturbations...
October 16, 2018: Neuron
Xin Chen, Siyi Wanggou, Ankur Bodalia, Min Zhu, Weifan Dong, Jerry J Fan, Wen Chi Yin, Hyun-Kee Min, Malini Hu, Diana Draghici, Wenkun Dou, Feng Li, Fiona J Coutinho, Heather Whetstone, Michelle M Kushida, Peter B Dirks, Yuanquan Song, Chi-Chung Hui, Yu Sun, Lu-Yang Wang, Xuejun Li, Xi Huang
Alteration of tissue mechanical properties is a physical hallmark of solid tumors including gliomas. How tumor cells sense and regulate tissue mechanics is largely unknown. Here, we show that mechanosensitive ion channel Piezo regulates mitosis and tissue stiffness of Drosophila gliomas, but not non-transformed brains. PIEZO1 is overexpressed in aggressive human gliomas and its expression inversely correlates with patient survival. Deleting PIEZO1 suppresses the growth of glioblastoma stem cells, inhibits tumor development, and prolongs mouse survival...
October 16, 2018: Neuron
Young J Kim, Sattar Khoshkhoo, Jan C Frankowski, Bingyao Zhu, Saad Abbasi, Sunyoung Lee, Ye Emily Wu, Robert F Hunt
Considerable evidence suggests loss-of-function mutations in the chromatin remodeler CHD2 contribute to a broad spectrum of human neurodevelopmental disorders. However, it is unknown how CHD2 mutations lead to impaired brain function. Here we report mice with heterozygous mutations in Chd2 exhibit deficits in neuron proliferation and a shift in neuronal excitability that included divergent changes in excitatory and inhibitory synaptic function. Further in vivo experiments show that Chd2+/- mice displayed aberrant cortical rhythmogenesis and severe deficits in long-term memory, consistent with phenotypes observed in humans...
October 13, 2018: Neuron
Elena Blanco-Suarez, Tong-Fei Liu, Alex Kopelevich, Nicola J Allen
In the developing brain, immature synapses contain calcium-permeable AMPA glutamate receptors (AMPARs) that are subsequently replaced with GluA2-containing calcium-impermeable AMPARs as synapses stabilize and mature. Here, we show that this essential switch in AMPARs and neuronal synapse maturation is regulated by astrocytes. Using biochemical fractionation of astrocyte-secreted proteins and mass spectrometry, we identified that astrocyte-secreted chordin-like 1 (Chrdl1) is necessary and sufficient to induce mature GluA2-containing synapses to form...
October 12, 2018: Neuron
Jane Y Chen, Carlos A Campos, Brooke C Jarvie, Richard D Palmiter
Food aversions develop when the taste of a novel food is associated with sickness, which often occurs after food poisoning or chemotherapy treatment. We identified calcitonin-gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) as sufficient and necessary for establishing a conditioned taste aversion (CTA). Photoactivating projections from CGRPPBN neurons to either the central nucleus of the amygdala or the bed nucleus of the stria terminalis can also induce robust CTA. CGRPPBN neurons undergo plasticity following CTA, and inactivation of either Arc or Grin1 (genes involved in memory consolidation) prevents establishment of a strong CTA...
October 11, 2018: Neuron
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