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Arjun Krishnan, Ran Zhang, Victoria Yao, Chandra L Theesfeld, Aaron K Wong, Alicja Tadych, Natalia Volfovsky, Alan Packer, Alex Lash, Olga G Troyanskaya
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic basis. Yet, only a small fraction of potentially causal genes-about 65 genes out of an estimated several hundred-are known with strong genetic evidence from sequencing studies. We developed a complementary machine-learning approach based on a human brain-specific gene network to present a genome-wide prediction of autism risk genes, including hundreds of candidates for which there is minimal or no prior genetic evidence...
November 2016: Nature Neuroscience
Gillian A Matthews, Edward H Nieh, Caitlin M Vander Weele, Sarah A Halbert, Roma V Pradhan, Ariella S Yosafat, Gordon F Glober, Ehsan M Izadmehr, Rain E Thomas, Gabrielle D Lacy, Craig P Wildes, Mark A Ungless, Kay M Tye
The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging...
February 11, 2016: Cell
Ada Eban-Rothschild, Gideon Rothschild, William J Giardino, Jeff R Jones, Luis de Lecea
Dopaminergic ventral tegmental area (VTA) neurons are critically involved in a variety of behaviors that rely on heightened arousal, but whether they directly and causally control the generation and maintenance of wakefulness is unknown. We recorded calcium activity using fiber photometry in freely behaving mice and found arousal-state-dependent alterations in VTA dopaminergic neurons. We used chemogenetic and optogenetic manipulations together with polysomnographic recordings to demonstrate that VTA dopaminergic neurons are necessary for arousal and that their inhibition suppresses wakefulness, even in the face of ethologically relevant salient stimuli...
October 2016: Nature Neuroscience
Melville J Wohlgemuth, Jinhong Luo, Cynthia F Moss
Echolocating bats exhibit accurate three-dimensional (3D) auditory localization to avoid obstacles and intercept prey. The bat achieves high spatial resolution through a biological sonar system. Key features of the bat's sonar system are (1) high frequency, directional echolocation signals; (2) high frequency hearing; (3) mobile ears; and (4) measurement of distance from the time delay between sonar emission and echo reception. The bat's sonar receiver is a standard mammalian auditory system that computes azimuth from inter-aural differences and elevation from spectral filtering by the ear [1-3]...
December 2016: Current Opinion in Neurobiology
S Montagud-Romero, M D Reguilon, C Roger-Sanchez, M Pascual, M A Aguilar, C Guerri, J Miñarro, M Rodríguez-Arias
Numerous studies report that social defeat stress alters dopamine (DA) neurotransmission in several areas of the brain. Alterations of the mesolimbic dopaminergic pathway are believed to be responsible for the increased vulnerability to drug use observed as a result of social stress. In the present study, we evaluated the influence of DA receptors on the long-term effect of repeated social defeat (RSD) on the conditioned rewarding and reinstating effects of cocaine. For this purpose, the D1R antagonist SCH 23390 and the D1R antagonist raclopride were administered 30min before each social defeat and a cocaine-induced CPP procedure was initiated three weeks later...
November 3, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Sebastiano Bariselli, Stamatina Tzanoulinou, Christelle Glangetas, Clément Prévost-Solié, Luca Pucci, Joanna Viguié, Paola Bezzi, Eoin C O'Connor, François Georges, Christian Lüscher, Camilla Bellone
Haploinsufficiency of SHANK3, encoding the synapse scaffolding protein SHANK3, leads to a highly penetrant form of autism spectrum disorder. How SHANK3 insufficiency affects specific neural circuits and how this is related to specific symptoms remains elusive. Here we used shRNA to model Shank3 insufficiency in the ventral tegmental area of mice. We identified dopamine (DA) and GABA cell-type-specific changes in excitatory synapse transmission that converge to reduce DA neuron activity and generate behavioral deficits, including impaired social preference...
July 2016: Nature Neuroscience
Erin L Rich, Jonathan D Wallis
When making a subjective choice, the brain must compute a value for each option and compare those values to make a decision. The orbitofrontal cortex (OFC) is critically involved in this process, but the neural mechanisms remain obscure, in part due to limitations in our ability to measure and control the internal deliberations that can alter the dynamics of the decision process. Here we tracked these dynamics by recovering temporally precise neural states from multidimensional data in OFC. During individual choices, OFC alternated between states associated with the value of two available options, with dynamics that predicted whether a subject would decide quickly or vacillate between the two alternatives...
July 2016: Nature Neuroscience
Steven J Middleton, Thomas J McHugh
In addition to the place-cell rate code, hippocampal area CA1 employs a temporal code, both on the single-cell and ensemble level, to accurately represent space. Although there is clear evidence that this precise spike timing is organized by theta and gamma oscillations that are present in hippocampus, the circuit mechanisms underlying these temporal codes remain poorly understood. We found that the loss of CA3 input abolished temporal coding at the ensemble level in CA1 despite the persistence of both rate and temporal coding in individual neurons...
July 2016: Nature Neuroscience
Andrei T Popescu, Michael R Zhou, Mu-Ming Poo
Phasic dopamine (DA) release is believed to guide associative learning. Most studies have focused on projections from the ventral tegmental area (VTA) to the striatum, and the action of DA in other VTA target regions remains unclear. Using optogenetic activation of VTA projections, we examined DA function in the medial prefrontal cortex (mPFC). We found that mice perceived optogenetically induced DA release in mPFC as neither rewarding nor aversive, and did not change their previously learned behavior in response to DA transients...
May 31, 2016: Proceedings of the National Academy of Sciences of the United States of America
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