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Lora B Sweeney, Jay B Bikoff, Mariano I Gabitto, Susan Brenner-Morton, Myungin Baek, Jerry H Yang, Esteban G Tabak, Jeremy S Dasen, Christopher R Kintner, Thomas M Jessell
Motor output varies along the rostro-caudal axis of the tetrapod spinal cord. At limb levels, ∼60 motor pools control the alternation of flexor and extensor muscles about each joint, whereas at thoracic levels as few as 10 motor pools supply muscle groups that support posture, inspiration, and expiration. Whether such differences in motor neuron identity and muscle number are associated with segmental distinctions in interneuron diversity has not been resolved. We show that select combinations of nineteen transcription factors that specify lumbar V1 inhibitory interneurons generate subpopulations enriched at limb and thoracic levels...
January 3, 2018: Neuron
Jeffrey M Donlea, Diogo Pimentel, Clifford B Talbot, Anissa Kempf, Jaison J Omoto, Volker Hartenstein, Gero Miesenböck
Sleep-promoting neurons in the dorsal fan-shaped body (dFB) of Drosophila are integral to sleep homeostasis, but how these cells impose sleep on the organism is unknown. We report that dFB neurons communicate via inhibitory transmitters, including allatostatin-A (AstA), with interneurons connecting the superior arch with the ellipsoid body of the central complex. These "helicon cells" express the galanin receptor homolog AstA-R1, respond to visual input, gate locomotion, and are inhibited by AstA, suggesting that dFB neurons promote rest by suppressing visually guided movement...
January 3, 2018: Neuron
Josh D Hawk, Ana C Calvo, Ping Liu, Agustin Almoril-Porras, Ahmad Aljobeh, María Luisa Torruella-Suárez, Ivy Ren, Nathan Cook, Joel Greenwood, Linjiao Luo, Zhao-Wen Wang, Aravinthan D T Samuel, Daniel A Colón-Ramos
Neural plasticity, the ability of neurons to change their properties in response to experiences, underpins the nervous system's capacity to form memories and actuate behaviors. How different plasticity mechanisms act together in vivo and at a cellular level to transform sensory information into behavior is not well understood. We show that in Caenorhabditis elegans two plasticity mechanisms-sensory adaptation and presynaptic plasticity-act within a single cell to encode thermosensory information and actuate a temperature preference memory...
January 2, 2018: Neuron
Hongbin Yang, Johannes W de Jong, YeEun Tak, James Peck, Helen S Bateup, Stephan Lammel
Mesolimbic dopamine (DA) neurons play a central role in motivation and reward processing. Although the activity of these mesolimbic DA neurons is controlled by afferent inputs, little is known about the circuits in which they are embedded. Using retrograde tracing, electrophysiology, optogenetics, and behavioral assays, we identify principles of afferent-specific control in the mesolimbic DA system. Neurons in the medial shell subdivision of the nucleus accumbens (NAc) exert direct inhibitory control over two separate populations of mesolimbic DA neurons by activating different GABA receptor subtypes...
December 30, 2017: Neuron
Brian R Isett, Sierra H Feasel, Monet A Lane, Daniel E Feldman
Tactile objects have both local geometry (shape) and broader macroscopic texture, but how these different spatial scales are simultaneously encoded during active touch is unknown. In the whisker system, we tested for a shared code based on localized whisker micromotions (stick-slips) and slip-evoked spikes. We trained mice to discriminate smooth from rough surfaces, including ridged gratings and sandpaper. Whisker slips locked to ridges and evoked temporally precise spikes (<10 ms jitter) in somatosensory cortex (S1) that could resolve ridges with ∼1 mm accuracy...
December 28, 2017: Neuron
Christian Madry, Vasiliki Kyrargyri, I Lorena Arancibia-Cárcamo, Renaud Jolivet, Shinichi Kohsaka, Robert M Bryan, David Attwell
Microglia exhibit two modes of motility: they constantly extend and retract their processes to survey the brain, but they also send out targeted processes to envelop sites of tissue damage. We now show that these motility modes differ mechanistically. We identify the two-pore domain channel THIK-1 as the main K+ channel expressed in microglia in situ. THIK-1 is tonically active, and its activity is potentiated by P2Y12 receptors. Inhibiting THIK-1 function pharmacologically or by gene knockout depolarizes microglia, which decreases microglial ramification and thus reduces surveillance, whereas blocking P2Y12 receptors does not affect membrane potential, ramification, or surveillance...
December 27, 2017: Neuron
Steeve Laquitaine, Justin L Gardner
Human perceptual inference has been fruitfully characterized as a normative Bayesian process in which sensory evidence and priors are multiplicatively combined to form posteriors from which sensory estimates can be optimally read out. We tested whether this basic Bayesian framework could explain human subjects' behavior in two estimation tasks in which we varied the strength of sensory evidence (motion coherence or contrast) and priors (set of directions or orientations). We found that despite excellent agreement of estimates mean and variability with a Basic Bayesian observer model, the estimate distributions were bimodal with unpredicted modes near the prior and the likelihood...
December 27, 2017: Neuron
R Becket Ebitz, Eddy Albarran, Tirin Moore
In uncertain environments, decision-makers must balance two goals: they must "exploit" rewarding options but also "explore" in order to discover rewarding alternatives. Exploring and exploiting necessarily change how the brain responds to identical stimuli, but little is known about how these states, and transitions between them, change how the brain transforms sensory information into action. To address this question, we recorded neural activity in a prefrontal sensorimotor area while monkeys naturally switched between exploring and exploiting rewarding options...
December 27, 2017: Neuron
Guang-Wei Zhang, Wen-Jian Sun, Brian Zingg, Li Shen, Jufang He, Ying Xiong, Huizhong W Tao, Li I Zhang
In the mammalian brain, auditory information is known to be processed along a central ascending pathway leading to auditory cortex (AC). Whether there exist any major pathways beyond this canonical auditory neuraxis remains unclear. In awake mice, we found that auditory responses in entorhinal cortex (EC) cannot be explained by a previously proposed relay from AC based on response properties. By combining anatomical tracing and optogenetic/pharmacological manipulations, we discovered that EC received auditory input primarily from the medial septum (MS), rather than AC...
December 21, 2017: Neuron
He Liu, Wenxing Yang, Taihong Wu, Fengyun Duan, Edward Soucy, Xin Jin, Yun Zhang
Sensorimotor integration regulates goal-directed movements. We study the signaling mechanisms underlying sensorimotor integration in C. elegans during olfactory steering, when the sinusoidal movements of the worm generate an in-phase oscillation in the concentration of the sampled odorant. We show that cholinergic neurotransmission encodes the oscillatory sensory response and the motor state of head undulations by acting through an acetylcholine-gated channel and a muscarinic acetylcholine receptor, respectively...
December 21, 2017: Neuron
Jakob Seidlitz, František Váša, Maxwell Shinn, Rafael Romero-Garcia, Kirstie J Whitaker, Petra E Vértes, Konrad Wagstyl, Paul Kirkpatrick Reardon, Liv Clasen, Siyuan Liu, Adam Messinger, David A Leopold, Peter Fonagy, Raymond J Dolan, Peter B Jones, Ian M Goodyer, Armin Raznahan, Edward T Bullmore
Macroscopic cortical networks are important for cognitive function, but it remains challenging to construct anatomically plausible individual structural connectomes from human neuroimaging. We introduce a new technique for cortical network mapping based on inter-regional similarity of multiple morphometric parameters measured using multimodal MRI. In three cohorts (two human, one macaque), we find that the resulting morphometric similarity networks (MSNs) have a complex topological organization comprising modules and high-degree hubs...
December 21, 2017: Neuron
Aryeh Hai Taub, Rita Perets, Eilat Kahana, Rony Paz
The contribution of oscillatory synchrony in the primate amygdala-prefrontal pathway to aversive learning remains largely unknown. We found increased power and phase synchrony in the theta range during aversive conditioning. The synchrony was linked to single-unit spiking and exhibited specific directionality between input and output measures in each region. Although it was correlated with the magnitude of conditioned responses, it declined once the association stabilized. The results suggest that amygdala spikes help to synchronize ACC activity and transfer error signal information to support memory formation...
December 20, 2017: Neuron
Friederike Zunke, Alexandra C Moise, Nandkishore R Belur, Eilrayna Gelyana, Iva Stojkovska, Haris Dzaferbegovic, Nicholas J Toker, Sohee Jeon, Kristina Fredriksen, Joseph R Mazzulli
α-Synuclein (α-syn) aggregation is a key event in Parkinson's disease (PD). Mutations in glycosphingolipid (GSL)-degrading glucocerebrosidase are risk factors for PD, indicating that disrupted GSL clearance plays a key role in α-syn aggregation. However, the mechanisms of GSL-induced aggregation are not completely understood. We document the presence of physiological α-syn conformers in human midbrain dopamine neurons and tested their contribution to the aggregation process. Pathological α-syn assembly mainly occurred through the conversion of high molecular weight (HMW) physiological α-syn conformers into compact, assembly-state intermediates by glucosylceramide (GluCer), without apparent disassembly into free monomers...
December 20, 2017: Neuron
Youngseok Lee, Seeta Poudel, Yunjung Kim, Dhananjay Thakur, Craig Montell
Many animals, ranging from vinegar flies to humans, discriminate a wide range of tastants, including sugars, bitter compounds, NaCl, and sour. However, the taste of Ca2+ is poorly understood, and it is unclear whether animals such as Drosophila melanogaster are endowed with this sense. Here, we examined Ca2+ taste in Drosophila and showed that high levels of Ca2+ are aversive. The repulsion was mediated by two mechanisms-activation of a specific class of gustatory receptor neurons (GRNs), which suppresses feeding and inhibition of sugar-activated GRNs, which normally stimulates feeding...
December 20, 2017: Neuron
Sora Shin, Horia Pribiag, Varoth Lilascharoen, Daniel Knowland, Xiao-Yun Wang, Byung Kook Lim
Early life stress (ELS) in the form of child abuse/neglect is associated with an increased risk of developing social dysfunction in adulthood. Little is known, however, about the neural substrates or the neuromodulatory signaling that govern ELS-induced social dysfunction. Here, we show that ELS-induced downregulation of dopamine receptor 3 (Drd3) signaling and its corresponding effects on neural activity in the lateral septum (LS) are both necessary and sufficient to cause social abnormalities in adulthood...
December 14, 2017: Neuron
Lou Beaulieu-Laroche, Mark T Harnett
Synapses are the fundamental units of information processing in the mammalian brain. Much of our understanding of their functional properties comes from voltage-clamp analysis, the predominant approach for investigating synaptic physiology. Here, we reveal that voltage clamp is completely ineffective for most excitatory synapses due to spine electrical compartmentalization. Under local dendritic voltage clamp, single-spine activation produced large spine head depolarizations that severely distorted measurements and recruited voltage-dependent channels...
December 13, 2017: Neuron
Dalila G Ordonez, Michael K Lee, Mel B Feany
Genetics and neuropathology strongly link α-synuclein aggregation and neurotoxicity to the pathogenesis of Parkinson's disease and related α-synucleinopathies. Here we describe a new Drosophila model of α-synucleinopathy based on widespread expression of wild-type human α-synuclein, which shows robust neurodegeneration, early-onset locomotor deficits, and abundant α-synuclein aggregation. We use results of forward genetic screening and genetic analysis in our new model to demonstrate that α-synuclein expression promotes reorganization of the actin filament network and consequent mitochondrial dysfunction through altered Drp1 localization...
December 13, 2017: Neuron
Randolph F Helfrich, Bryce A Mander, William J Jagust, Robert T Knight, Matthew P Walker
The coupled interaction between slow-wave oscillations and sleep spindles during non-rapid-eye-movement (NREM) sleep has been proposed to support memory consolidation. However, little evidence in humans supports this theory. Moreover, whether such dynamic coupling is impaired as a consequence of brain aging in later life, contributing to cognitive and memory decline, is unknown. Combining electroencephalography (EEG), structural MRI, and sleep-dependent memory assessment, we addressed these questions in cognitively normal young and older adults...
December 12, 2017: Neuron
Pierre Le Merre, Vahid Esmaeili, Eloïse Charrière, Katia Galan, Paul-A Salin, Carl C H Petersen, Sylvain Crochet
The neural circuits underlying learning and execution of goal-directed behaviors remain to be determined. Here, through electrophysiological recordings, we investigated fast sensory processing across multiple cortical areas as mice learned to lick a reward spout in response to a brief deflection of a single whisker. Sensory-evoked signals were absent from medial prefrontal cortex and dorsal hippocampus in naive mice, but developed with task learning and correlated with behavioral performance in mice trained in the detection task...
December 12, 2017: Neuron
Alvin Yu, Héctor Salazar, Andrew J R Plested, Albert Y Lau
Ionotropic glutamate receptors (iGluRs) mediate neurotransmission at the majority of excitatory synapses in the brain. Little is known, however, about how glutamate reaches the recessed binding pocket in iGluR ligand-binding domains (LBDs). Here we report the process of glutamate binding to a prototypical iGluR, GluA2, in atomistic detail using unbiased molecular simulations. Charged residues on the LBD surface form pathways that facilitate glutamate binding by effectively reducing a three-dimensional diffusion process to a spatially constrained, two-dimensional one...
December 12, 2017: Neuron
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