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Neuroscience
Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease
May 18, 2017   PloS One
Caspell-Garcia C, Simuni T, Tosun-Turgut D, Wu IW, Zhang Y,   . . . . . .   , Hawkins KA, Litvan I, Richard I, Weintraub D, Parkinson’s Progression Markers Initiative (PPMI)
Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease
May 18, 2017
PloS One
To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments. We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition. Additionally, longitudinal structural MRI and DAT scan data were included. Univariate analyses were run initially, with false discovery rate = 0.2, to select biomarker variables for inclusion in multivariable longitudinal mixed-effect models. By year 3, cognitive impairment was diagnosed in 15-38% participants depending on the criteria applied. Biomarkers, some longitudinal, predicting cognitive impairment in multivariable models were: (1) dopamine deficiency (decreased caudate and putamen DAT availability); (2) diffuse, cortical decreased brain volume or thickness (frontal, temporal, parietal, and occipital lobe regions); (3) co-morbid Alzheimer's disease Aβ amyloid pathology (lower CSF Aβ 1-42); and (4) genes (COMT val/val and BDNF val/val genotypes). Cognitive impairment in PD increases in frequency 50-200% in the first several years of disease, and is independently predicted by biomarker changes related to nigrostriatal or cortical dopaminergic deficits, global atrophy due to possible widespread effects of neurodegenerative disease, co-morbid Alzheimer's disease plaque pathology, and genetic factors.
Dopamine Depletion Impairs Bilateral Sensory Processing in the Striatum in a Pathway-Dependent Manner
May 18, 2017   Neuron
Ketzef M, Spigolon G, Johansson Y, Bonito-Oliva A, Fisone G, Silberberg G
Dopamine Depletion Impairs Bilateral Sensory Processing in the Striatum in a Pathway-Dependent Manner
May 18, 2017
Neuron
Parkinson's disease (PD) is a movement disorder caused by the loss of dopaminergic innervation, particularly to the striatum. PD patients often exhibit sensory impairments, yet the underlying network mechanisms are unknown. Here we examined how dopamine (DA) depletion affects sensory processing in the mouse striatum. We used the optopatcher for online identification of direct and indirect pathway projection neurons (MSNs) during in vivo whole-cell recordings. In control mice, MSNs encoded the laterality of sensory inputs with larger and earlier responses to contralateral than ipsilateral whisker deflection. This laterality coding was lost in DA-depleted mice due to adaptive changes in the intrinsic and synaptic properties, mainly, of direct pathway MSNs. L-DOPA treatment restored laterality coding by increasing the separation between ipsilateral and contralateral responses. Our results show that DA depletion impairs bilateral tactile acuity in a pathway-dependent manner, thus providing unexpected insights into the network mechanisms underlying sensory deficits in PD. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.
Mechanisms of Orientation Selectivity in the Primary Visual Cortex
May 23, 2017   Annual Review Of Vision Science
Priebe NJ
Mechanisms of Orientation Selectivity in the Primary Visual Cortex
May 23, 2017
Annual Review Of Vision Science
The mechanisms underlying the emergence of orientation selectivity in the visual cortex have been, and continue to be, the subjects of intense scrutiny. Orientation selectivity reflects a dramatic change in the representation of the visual world: Whereas afferent thalamic neurons are generally orientation insensitive, neurons in the primary visual cortex (V1) are extremely sensitive to stimulus orientation. This profound change in the receptive field structure along the visual pathway has positioned V1 as a model system for studying the circuitry that underlies neural computations across the neocortex. The neocortex is characterized anatomically by the relative uniformity of its circuitry despite its role in processing distinct signals from region to region. A combination of physiological, anatomical, and theoretical studies has shed some light on the circuitry components necessary for generating orientation selectivity in V1. This targeted effort has led to critical insights, as well as controversies, concerning how neural circuits in the neocortex perform computations.
Hick-Hyman Law is Mediated by the Cognitive Control Network in the Brain
May 22, 2017   Cerebral Cortex (New York, N.Y. : 1991)
Wu T, Dufford AJ, Egan LJ, Mackie MA, Chen C, Yuan C, Chen C, Li X, Liu X, Hof PR, Fan J
Hick-Hyman Law is Mediated by the Cognitive Control Network in the Brain
May 22, 2017
Cerebral Cortex (New York, N.Y. : 1991)
The Hick-Hyman law describes a linear increase in reaction time (RT) as a function of the information entropy of response selection, which is computed as the binary logarithm of the number of response alternatives. While numerous behavioral studies have provided evidence for the Hick-Hyman law, its neural underpinnings have rarely been examined and are still unclear. In this functional magnetic resonance imaging study, by utilizing a choice reaction time task to manipulate the entropy of response selection, we examined brain activity mediating the input and the output, as well as the connectivity between corresponding regions in human participants. Beyond confirming the Hick-Hyman law in RT performance, we found that activation of the cognitive control network (CCN) increased and activation of the default mode network (DMN) decreased, both as a function of entropy. However, only the CCN, but not the DMN, was involved in mediating the relationship between entropy and RT. The CCN was involved in both stages of uncertainty representation and response generation, while the DMN was mainly involved at the stage of uncertainty representation. These findings indicate that the CCN serves as a core entity underlying the Hick-Hyman law by coordinating uncertainty representation and response generation in the brain. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence
May 22, 2017   Nature Genetics Add nature.com free-link Cancel
Sniekers S, Stringer S, Watanabe K, Jansen PR, Coleman JRI,   . . . . . .   , Plomin R, Rietveld CA, Tiemeier H, van Duijn CM, Posthuma D
Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence
May 22, 2017
Nature Genetics
Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10-8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10-6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10-6). Despite the well-known difference in twin-based heratiblity for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10-29). These findings provide new insight into the genetic architecture of intelligence.
Flexible information routing by transient synchrony
May 22, 2017   Nature Neuroscience Add nature.com free-link Cancel
Palmigiano A, Geisel T, Wolf F, Battaglia D
Flexible information routing by transient synchrony
May 22, 2017
Nature Neuroscience
Perception, cognition and behavior rely on flexible communication between microcircuits in distinct cortical regions. The mechanisms underlying rapid information rerouting between such microcircuits are still unknown. It has been proposed that changing patterns of coherence between local gamma rhythms support flexible information rerouting. The stochastic and transient nature of gamma oscillations in vivo, however, is hard to reconcile with such a function. Here we show that models of cortical circuits near the onset of oscillatory synchrony selectively route input signals despite the short duration of gamma bursts and the irregularity of neuronal firing. In canonical multiarea circuits, we find that gamma bursts spontaneously arise with matched timing and frequency and that they organize information flow by large-scale routing states. Specific self-organized routing states can be induced by minor modulations of background activity.
A cerebellum-like circuit in the auditory system cancels responses to self-generated sounds
May 22, 2017   Nature Neuroscience Add nature.com free-link Cancel
Singla S, Dempsey C, Warren R, Enikolopov AG, Sawtell NB
A cerebellum-like circuit in the auditory system cancels responses to self-generated sounds
May 22, 2017
Nature Neuroscience
The dorsal cochlear nucleus (DCN) integrates auditory nerve input with a diverse array of sensory and motor signals processed in circuitry similar to that of the cerebellum. Yet how the DCN contributes to early auditory processing has been a longstanding puzzle. Using electrophysiological recordings in mice during licking behavior, we show that DCN neurons are largely unaffected by self-generated sounds while remaining sensitive to external acoustic stimuli. Recordings in deafened mice, together with neural activity manipulations, indicate that self-generated sounds are cancelled by non-auditory signals conveyed by mossy fibers. In addition, DCN neurons exhibit gradual reductions in their responses to acoustic stimuli that are temporally correlated with licking. Together, these findings suggest that DCN may act as an adaptive filter for cancelling self-generated sounds. Adaptive filtering has been established previously for cerebellum-like sensory structures in fish, suggesting a conserved function for such structures across vertebrates.
Decomposing Tool-Action Observation: A Stereo-EEG Study
May 19, 2017   Cerebral Cortex (New York, N.Y. : 1991)
Caruana F, Avanzini P, Mai R, Pelliccia V, LoRusso G, Rizzolatti G, Orban GA
Decomposing Tool-Action Observation: A Stereo-EEG Study
May 19, 2017
Cerebral Cortex (New York, N.Y. : 1991)
A description of the spatiotemporal dynamics of human cortical activity during cognitive tasks is a fundamental goal of neuroscience. In the present study, we employed stereo-EEG in order to assess the neural activity during tool-action observation. We recorded from 49 epileptic patients (5502 leads) implanted with intracerebral electrodes, while they observed tool and hand actions. We deconstructed actions into 3 events-video onset, action onset, and tool-object contact-and assessed how different brain regions respond to these events. Video onset, with actions not yet visible, recruited only visual areas. Aligning the responses at action onset, yielded activity in the parietal-frontal manipulation circuit and, selectively for tool actions, in the left anterior supramarginal gyrus (aSMG). Finally, by aligning to the tool-object contact that signals the achievement of the main goal of the observed action, activations were found in SII and dorsal premotor cortex. In conclusion, our data show that during tool-action observation, in addition to the general action observation network there is a selective activation of aSMG, which exhibits internally different patterns of responsiveness. In addition, neural responses selective for the contact between the tool and the object were also observed. © The Author 2017. Published by Oxford University Press.
A Schizophrenia-Related Deletion Leads to KCNQ2-Dependent Abnormal Dopaminergic Modulation of Prefrontal Cortical Interneuron Activity
May 19, 2017   Cerebral Cortex (New York, N.Y. : 1991)
Choi SJ, Mukai J, Kvajo M, Xu B, Diamantopoulou A, Pitychoutis PM, Gou B, Gogos JA, Zhang H
A Schizophrenia-Related Deletion Leads to KCNQ2-Dependent Abnormal Dopaminergic Modulation of Prefrontal Cortical Interneuron Activity
May 19, 2017
Cerebral Cortex (New York, N.Y. : 1991)
Altered prefrontal cortex function is implicated in schizophrenia (SCZ) pathophysiology and could arise from imbalance between excitation and inhibition (E/I) in local circuits. It remains unclear whether and how such imbalances relate to genetic etiologies. We used a mouse model of the SCZ-predisposing 22q11.2 deletion (Df(16)A+/- mice) to evaluate how this genetic lesion affects the excitability of layer V prefrontal pyramidal neurons and its modulation by dopamine (DA). Df(16)A+/- mice have normal balance between E/I at baseline but are unable to maintain it upon dopaminergic challenge. Specifically, in wild-type mice, D1 receptor (D1R) activation enhances excitability of layer V prefrontal pyramidal neurons and D2 receptor (D2R) activation reduces it. Whereas the excitatory effect upon D1R activation is enhanced in Df(16)A+/- mice, the inhibitory effect upon D2R activation is reduced. The latter is partly due to the inability of mutant mice to activate GABAergic parvalbumin (PV)+ interneurons through D2Rs. We further demonstrate that reduced KCNQ2 channel function in PV+ interneurons in Df(16)A+/- mice renders them less capable of inhibiting pyramidal neurons upon D2 modulation. Thus, DA modulation of PV+ interneurons and control of E/I are altered in Df(16)A+/- mice with a higher excitation and lower inhibition during dopaminergic modulation. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
The etiology of autistic traits in preschoolers: a population-based twin study
May 19, 2017   Journal Of Child Psychology And Psychiatry, And Allied Disciplines
de Zeeuw EL, van Beijsterveldt CEM, Hoekstra RA, Bartels M, Boomsma DI
The etiology of autistic traits in preschoolers: a population-based twin study
May 19, 2017
Journal Of Child Psychology And Psychiatry, And Allied Disciplines
Autism Spectrum Disorders (ASD) are highly heritable, but the exact etiological mechanisms underlying the condition are still unclear. Using a multiple rater twin design in a large sample of general population preschool twins, this study aimed to (a) estimate the contribution of genetic and environmental factors to autistic traits, controlling for the possible effects of rater bias, (b) to explore possible sex differences in etiology and (c) to investigate the discordance in autistic traits in monozygotic and same-sex dizygotic twin pairs. The Netherlands Twin Register collected maternal and paternal ratings on autistic traits from a general population of 38,798 three-year-old twins. Autistic traits were assessed with the DSM-oriented Pervasive Developmental Problems scale of the Child Behavior Check List for preschoolers (1½-5 years). Mother and fathers showed high agreement in their assessment of autistic traits (r = .60-.66). Differences between children in autistic traits were largely accounted for by genetic effects (boys: 78% and girls: 83%). Environmental effects that are unique to a child also played a modest role. Environmental effects shared by children growing up in the same family were negligible, once rater bias was controlled for. While the prevalence for clinical ASD is higher in boys than in girls, this study did not find evidence for striking differences in the etiology of autistic traits across the sexes. Even though the heritability was high, 29% of MZ twin pairs were discordant for high autistic traits (clinical range vs. normal development), suggesting that despite high genetic risk, environmental factors might lead to resilience, unaffected status in the context of genetic risk, in some children. It is important to focus future research on risk factors that might interplay with a genetic disposition for ASD, but also on protective factors that make a difference in the lives of children at genetic risk. © 2017 Association for Child and Adolescent Mental Health.
Indirect Pathway of Caudal Basal Ganglia for Rejection of Valueless Visual Objects
May 18, 2017   Neuron
Kim HF, Amita H, Hikosaka O
Indirect Pathway of Caudal Basal Ganglia for Rejection of Valueless Visual Objects
May 18, 2017
Neuron
The striatum controls behavior in two ways: facilitation and suppression through the direct and indirect pathways, respectively. However, it is still unclear what information is processed in these pathways. To address this question, we studied two pathways originating from the primate caudate tail (CDt). We found that the CDt innervated the caudal-dorsal-lateral part of the substantia nigra pars reticulata (cdlSNr), directly or indirectly through the caudal-ventral part of the globus pallidus externus (cvGPe). Notably, cvGPe neurons receiving inputs from the CDt were mostly visual neurons that encoded stable reward values of visual objects based on long-past experiences. Their dominant response was inhibition by valueless objects, which generated disinhibition of cdlSNr neurons and inhibition of superior colliculus neurons. Our data suggest that low-value signals are sent by the CDt-indirect pathway to suppress saccades to valueless objects, whereas high-value signals are sent by the CDt-direct pathway to facilitate saccades to valuable objects. Copyright © 2017 Elsevier Inc. All rights reserved.
A Map of Anticipatory Activity in Mouse Motor Cortex
May 18, 2017   Neuron
Chen TW, Li N, Daie K, Svoboda K
A Map of Anticipatory Activity in Mouse Motor Cortex
May 18, 2017
Neuron
Activity in the mouse anterior lateral motor cortex (ALM) instructs directional movements, often seconds before movement initiation. It is unknown whether this preparatory activity is localized to ALM or widely distributed within motor cortex. Here we imaged activity across motor cortex while mice performed a whisker-based object localization task with a delayed, directional licking response. During tactile sensation and the delay epoch, object location was represented in motor cortex areas that are medial and posterior relative to ALM, including vibrissal motor cortex. Preparatory activity appeared first in deep layers of ALM, seconds before the behavioral response, and remained localized to ALM until the behavioral response. Later, widely distributed neurons represented the outcome of the trial. Cortical area was more predictive of neuronal selectivity than laminar location or axonal projection target. Motor cortex therefore represents sensory, motor, and outcome information in a spatially organized manner. Copyright © 2017 Elsevier Inc. All rights reserved.
Dynamic Palmitoylation Targets MAP6 to the Axon to Promote Microtubule Stabilization during Neuronal Polarization
May 18, 2017   Neuron
Tortosa E, Adolfs Y, Fukata M, Pasterkamp RJ, Kapitein LC, Hoogenraad CC
Dynamic Palmitoylation Targets MAP6 to the Axon to Promote Microtubule Stabilization during Neuronal Polarization
May 18, 2017
Neuron
Microtubule-associated proteins (MAPs) are main candidates to stabilize neuronal microtubules, playing an important role in establishing axon-dendrite polarity. However, how MAPs are selectively targeted to specific neuronal compartments remains poorly understood. Here, we show specific localization of microtubule-associated protein 6 (MAP6)/stable tubule-only polypeptide (STOP) throughout neuronal maturation and its role in axonal development. In unpolarized neurons, MAP6 is present at the Golgi complex and in secretory vesicles. As neurons mature, MAP6 is translocated to the proximal axon, where it binds and stabilizes microtubules. Further, we demonstrate that dynamic palmitoylation, mediated by the family of α/β Hydrolase domain-containing protein 17 (ABHD17A-C) depalmitoylating enzymes, controls shuttling of MAP6 between membranes and microtubules and is required for MAP6 retention in axons. We propose a model in which MAP6's palmitoylation mediates microtubule stabilization, allows efficient organelle trafficking, and controls axon maturation in vitro and in situ. Copyright © 2017 Elsevier Inc. All rights reserved.
Atypical Endocannabinoid Signaling Initiates a New Form of Memory-Related Plasticity at a Cortical Input to Hippocampus
May 18, 2017   Cerebral Cortex (New York, N.Y. : 1991)
Wang W, Jia Y, Pham DT, Palmer LC, Jung KM, Cox CD, Rumbaugh G, Piomelli D, Gall CM, Lynch G
Atypical Endocannabinoid Signaling Initiates a New Form of Memory-Related Plasticity at a Cortical Input to Hippocampus
May 18, 2017
Cerebral Cortex (New York, N.Y. : 1991)
Endocannabinoids (ECBs) depress transmitter release at sites throughout the brain. Here, we describe another form of ECB signaling that triggers a novel form of long-term potentiation (LTP) localized to the lateral perforant path (LPP) which conveys semantic information from cortex to hippocampus. Two cannabinoid CB1 receptor (CB1R) signaling cascades were identified in hippocampus. The first is pregnenolone sensitive, targets vesicular protein Munc18-1 and depresses transmitter release; this cascade is engaged by CB1Rs in Schaffer-Commissural afferents to CA1 but not in the LPP, and it does not contribute to LTP. The second cascade is pregnenolone insensitive and LPP specific; it entails co-operative CB1R/β1-integrin signaling to effect synaptic potentiation via stable enhancement of transmitter release. The latter cascade is engaged during LPP-dependent learning. These results link atypical ECB signaling to the encoding of a fundamental component of episodic memory and suggest a novel route whereby endogenous and exogenous cannabinoids affect cognition. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
CaMKII Autophosphorylation Is Necessary for Optimal Integration of Ca2+ Signals during LTP Induction, but Not Maintenance
May 18, 2017   Neuron
Chang JY, Parra-Bueno P, Laviv T, Szatmari EM, Lee SR, Yasuda R
CaMKII Autophosphorylation Is Necessary for Optimal Integration of Ca2+ Signals during LTP Induction, but Not Maintenance
May 18, 2017
Neuron
CaMKII plays a critical role in decoding calcium (Ca2+) signals to initiate long-lasting synaptic plasticity. However, the properties of CaMKII that mediate Ca2+ signals in spines remain elusive. Here, we measured CaMKII activity in spines using fast-framing two-photon fluorescence lifetime imaging. Following each pulse during repetitive Ca2+ elevations, CaMKII activity increased in a stepwise manner. Thr286 phosphorylation slows the decay of CaMKII and thus lowers the frequency required to induce spine plasticity by several fold. In the absence of Thr286 phosphorylation, increasing the stimulation frequency results in high peak mutant CaMKIIT286A activity that is sufficient for inducing plasticity. Our findings demonstrate that Thr286 phosphorylation plays an important role in induction of LTP by integrating Ca2+ signals, and it greatly promotes, but is dispensable for, the activation of CaMKII and LTP. Copyright © 2017 Elsevier Inc. All rights reserved.
Linking Neurons to Network Function and Behavior by Two-Photon Holographic Optogenetics and Volumetric Imaging
May 18, 2017   Neuron
Dal Maschio M, Donovan JC, Helmbrecht TO, Baier H
Linking Neurons to Network Function and Behavior by Two-Photon Holographic Optogenetics and Volumetric Imaging
May 18, 2017
Neuron
We introduce a flexible method for high-resolution interrogation of circuit function, which combines simultaneous 3D two-photon stimulation of multiple targeted neurons, volumetric functional imaging, and quantitative behavioral tracking. This integrated approach was applied to dissect how an ensemble of premotor neurons in the larval zebrafish brain drives a basic motor program, the bending of the tail. We developed an iterative photostimulation strategy to identify minimal subsets of channelrhodopsin (ChR2)-expressing neurons that are sufficient to initiate tail movements. At the same time, the induced network activity was recorded by multiplane GCaMP6 imaging across the brain. From this dataset, we computationally identified activity patterns associated with distinct components of the elicited behavior and characterized the contributions of individual neurons. Using photoactivatable GFP (paGFP), we extended our protocol to visualize single functionally identified neurons and reconstruct their morphologies. Together, this toolkit enables linking behavior to circuit activity with unprecedented resolution. Copyright © 2017 Elsevier Inc. All rights reserved.
Integrating Results across Methodologies Is Essential for Producing Robust Neuronal Taxonomies
May 18, 2017   Neuron
Cembrowski MS, Spruston N
Integrating Results across Methodologies Is Essential for Producing Robust Neuronal Taxonomies
May 18, 2017
Neuron
Elucidating the diversity and spatial organization of cell types in the brain is an essential goal of neuroscience, with many emerging technologies helping to advance this endeavor. Using a new in situ hybridization method that can measure the expression of hundreds of genes in a given mouse brain section (amplified seqFISH), Shah et al. (2016) describe a spatial organization of hippocampal cell types that differs from previous reports. In seeking to understand this discrepancy, we find that many of the barcoded genes used by seqFISH to characterize this spatial organization, when cross-validated by other sensitive methodologies, exhibit negligible expression in the hippocampus. Additionally, the results of Shah et al. (2016) do not recapitulate canonical cellular hierarchies and improperly classify major neuronal cell types. We suggest that, when describing the spatial organization of brain regions, cross-validation using multiple techniques should be used to yield robust and informative cellular classification. This Matters Arising paper is in response to Shah et al. (2016), published in Neuron. See also the response by Shah et al. (2017), published in this issue. Copyright © 2017 Elsevier Inc. All rights reserved.
Synaptic Plasticity, Engrams, and Network Oscillations in Amygdala Circuits for Storage and Retrieval of Emotional Memories
May 18, 2017   Neuron
Bocchio M, Nabavi S, Capogna M
Synaptic Plasticity, Engrams, and Network Oscillations in Amygdala Circuits for Storage and Retrieval of Emotional Memories
May 18, 2017
Neuron
The neuronal circuits of the basolateral amygdala (BLA) are crucial for acquisition, consolidation, retrieval, and extinction of associative emotional memories. Synaptic plasticity in BLA neurons is essential for associative emotional learning and is a candidate mechanism through which subsets of BLA neurons (commonly termed "engram") are recruited during learning and reactivated during memory retrieval. In parallel, synchronous oscillations in the theta and gamma bands between the BLA and interconnected structures have been shown to occur during consolidation and retrieval of emotional memories. Understanding how these cellular and network phenomena interact is vital to decipher the roles of emotional memory formation and storage in the healthy and pathological brain. Here, we review data on synaptic plasticity, engrams, and network oscillations in the rodent BLA. We explore mechanisms through which synaptic plasticity, engrams, and long-range synchrony might be interconnected. Copyright © 2017 Elsevier Inc. All rights reserved.
Structural and Functional Architecture of AMPA-Type Glutamate Receptors and Their Auxiliary Proteins
May 18, 2017   Neuron
Greger IH, Watson JF, Cull-Candy SG
Structural and Functional Architecture of AMPA-Type Glutamate Receptors and Their Auxiliary Proteins
May 18, 2017
Neuron
AMPA receptors (AMPARs) are tetrameric ion channels that together with other ionotropic glutamate receptors (iGluRs), the NMDA and kainate receptors, mediate a majority of excitatory neurotransmission in the central nervous system. Whereas NMDA receptors gate channels with slow kinetics, responsible primarily for generating long-term synaptic potentiation and depression, AMPARs are the main fast transduction elements at synapses and are critical for the expression of plasticity. The kinetic and conductance properties of AMPARs are laid down during their biogenesis and are regulated by post-transcriptional RNA editing, splice variation, post-translational modification, and subunit composition. Furthermore, AMPAR assembly, trafficking, and functional heterogeneity depends on a large repertoire of auxiliary subunits-a feature that is particularly striking for this type of iGluR. Here, we discuss how the subunit structure, stoichiometry, and auxiliary subunits generate a heterogeneous plethora of receptors, each tailored to fulfill a vital role in fast synaptic signaling and plasticity. Copyright © 2017 Elsevier Inc. All rights reserved.
Beyond Hat in Hand: Science Advocacy Is Foundational for Policy Decisions
May 18, 2017   Neuron
Kendall-Taylor N, Levitt P
Beyond Hat in Hand: Science Advocacy Is Foundational for Policy Decisions
May 18, 2017
Neuron
Beyond those to whom neuroscientists typically communicate exciting discoveries-that is, those who can provide more funding for researchers-there are important audiences that are positioned to use neuroscience findings to affect policy and improve societal outcomes. Showing the utility of research that policymakers, service providers, and the public can use to make decisions will enhance views of the value of scientific research. The ingredients of successful communications between neuroscientists and other stakeholders are different from those that characterize effective communications between scientists. Here, we discuss our experiences in the communication of the science of early childhood and brain development and our recommendations to help neuroscientists better communicate the benefits of their research to those who make practice and policy decisions. Copyright © 2017 Elsevier Inc. All rights reserved.
Rat mPFC and M2 Play a Waiting Game (at Different Timescales)
May 18, 2017   Neuron
Langdon AJ, Wikenheiser AM, Schoenbaum G
Rat mPFC and M2 Play a Waiting Game (at Different Timescales)
May 18, 2017
Neuron
In this issue of Neuron, Murakami et al. (2017) relate neural activity in frontal cortex to stochastic and deterministic components of waiting behavior in rats; they find that mPFC biases waiting time, while M2 is ultimately responsible for trial-to-trial variability in decisions about how long to wait. Published by Elsevier Inc.
Ready, Steady, Go! Imaging Cortical Activity during Movement Planning and Execution
May 18, 2017   Neuron
Banerjee A, Long MA
Ready, Steady, Go! Imaging Cortical Activity during Movement Planning and Execution
May 18, 2017
Neuron
In this issue of Neuron, Chen et al. (2017) examine premotor activity representing motor planning, Allen et al. (2017) observe the global representation of goal-directed movement on the cortical network, and Makino et al. (2017) track changes in such dynamics throughout learning. Copyright © 2017 Elsevier Inc. All rights reserved.
Netrin-Mediated Axon Guidance to the CNS Midline Revisited
May 18, 2017   Neuron
Hand RA, Kolodkin AL
Netrin-Mediated Axon Guidance to the CNS Midline Revisited
May 18, 2017
Neuron
Varadarajan et al. (2017)-in this issue of Neuron-and Dominici et al. (2017)-published online at Nature-independently show that floor plate-derived netrin-1 is dispensable for commissural neuron axon guidance to the CNS midline during development. Copyright © 2017 Elsevier Inc. All rights reserved.
Computing the Social Brain Connectome Across Systems and States
May 18, 2017   Cerebral Cortex (New York, N.Y. : 1991)
Alcalá-López D, Smallwood J, Jefferies E, Van Overwalle F, Vogeley K, Mars RB, Turetsky BI, Laird AR, Fox PT, Eickhoff SB, Bzdok D
Computing the Social Brain Connectome Across Systems and States
May 18, 2017
Cerebral Cortex (New York, N.Y. : 1991)
Social skills probably emerge from the interaction between different neural processing levels. However, social neuroscience is fragmented into highly specialized, rarely cross-referenced topics. The present study attempts a systematic reconciliation by deriving a social brain definition from neural activity meta-analyses on social-cognitive capacities. The social brain was characterized by meta-analytic connectivity modeling evaluating coactivation in task-focused brain states and physiological fluctuations evaluating correlations in task-free brain states. Network clustering proposed a functional segregation into (1) lower sensory, (2) limbic, (3) intermediate, and (4) high associative neural circuits that together mediate various social phenomena. Functional profiling suggested that no brain region or network is exclusively devoted to social processes. Finally, nodes of the putative mirror-neuron system were coherently cross-connected during tasks and more tightly coupled to embodied simulation systems rather than abstract emulation systems. These first steps may help reintegrate the specialized research agendas in the social and affective sciences. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
N-acetylaspartylglutamate Inhibits Heroin Self-Administration and Heroin-Seeking Behaviors Induced by Cue or Priming in Rats
May 23, 2017   Neuroscience Bulletin
Zhu H, Lai M, Chen W, Mei D, Zhang F, Liu H, Zhou W
N-acetylaspartylglutamate Inhibits Heroin Self-Administration and Heroin-Seeking Behaviors Induced by Cue or Priming in Rats
May 23, 2017
Neuroscience Bulletin
Activation of presynaptic group II metabotropic glutamate receptors (mGluR2/3) inhibits drug reward and drug-seeking behavior, but the role of N-acetylaspartylglutamate (NAAG), an agonist of endogenous mGluR2/3, in heroin reward and heroin-seeking behavior remained unclear. Here, we aimed to explore the effects of exogenous NAAG on heroin self-administration and heroin-seeking behavior. First, rats were trained to self-administer heroin under a fixed ratio 1 (FR1) schedule for 10 days, then received NAAG (50 or 100 μg/10 μL in each nostril) in the absence or presence of LY341495 (1 mg/kg, i.p.), an antagonist of mGluR2/3, on day 11 and the effects of NAAG on heroin self-administration under FR1 were recorded for 3 consecutive days. Motivation was assessed in heroin self-administration under a progressive ratio schedule on day 11 in another 5 groups with the same doses of NAAG. Additional rats were withdrawn for 14 days after 14 days of heroin self-administration, then received the same pharmacological pretreatment and were tested for heroin-seeking behaviors induced by heroin priming or cues. The results showed that intranasal administration of NAAG significantly decreased intravenous heroin self-administration on day 12, but not on day 11. Pretreatment with LY341495 prior to testing on day 12 prevented the inhibitory effect of NAAG on heroin reinforcement. The break-point for reward motivation was significantly reduced by NAAG. Moreover, NAAG also significantly inhibited the heroin-seeking behaviors induced by heroin priming or cues and these were restored by pretreatment with LY341495. These results demonstrated that NAAG, via activation of presynaptic mGluR2/3, attenuated the heroin reinforcement, heroin motivational value, and heroin-seeking behavior, suggesting that it may be used as an adjunct treatment for heroin addiction.

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