Journal Sciences News
Revue Francophone des Laboratoires
August 2018
Towards resolving the presynaptic NMDA receptor debate
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Guy Bouvier, Rylan S Larsen, Antonio Rodr
August 2018
Creating diverse synapses from the same molecules
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Zoltan Nusser Research over the past half a century has revealed remarkable diversity among chemical synapses of the CNS. The structural, functional and molecular diversity of synapses was mainly concluded from studying different synapses in distinct brain regions and preparations. It is not surprising that synapses made by molecularly distinct pre-synaptic and post-synaptic cells display different morphological and functional properties with distinct underlying molecular mechanisms. However, synapses made by a single presynaptic cell onto distinct types of postsynaptic cells, or distinct presynaptic inputs onto a single postsynaptic cell, also show remarkable heterogeneity. Here, by reviewing recent experiments, I suggest that robust functional diversity can be achieved by building synapses from the same molecules, but using different numbers, densities and nanoscale arrangements.
June 2018
Functional implications of inhibitory synapse placement on signal processing in pyramidal neuron dendrites
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Josiah R Boivin, Elly Nedivi A rich literature describes inhibitory innervation of pyramidal neurons in terms of the distinct inhibitory cell types that target the soma, axon initial segment, or dendritic arbor. Less attention has been devoted to how localization of inhibition to specific parts of the pyramidal dendritic arbor influences dendritic signal detection and integration. The effect of inhibitory inputs can vary based on their placement on dendritic spines versus shaft, their distance from the soma, and the branch order of the dendrite they inhabit. Inhibitory synapses are also structurally dynamic, and the implications of these dynamics depend on their dendritic location. Here we consider the heterogeneous roles of inhibitory synapses as defined by their strategic placement on the pyramidal cell dendritic arbor.
June 2018
Investigation of brain science and neurological/psychiatric disorders using genetically modified non-human primates
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Hideyuki Okano, Noriyuki Kishi Although mice have been the most frequently used experimental animals in many research fields due to well-established gene manipulation techniques, recent evidence has revealed that rodent models do not always recapitulate pathophysiology of human neurological and psychiatric diseases due to the differences between humans and rodents. The recent developments in gene manipulation of non-human primate have been attracting much attention in the biomedical research field, because non-human primates have more applicable brain structure and function than rodents. In this review, we summarize recent progress on genetically-modified non-human primates including transgenic and knockout animals using genome editing technology.
June 2018
Neural lineage tracing in the mammalian brain
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Jian Ma, Zhongfu Shen, Yong-Chun Yu, Song-Hai Shi Delineating the lineage of neural cells that captures the progressive steps in their specification is fundamental to understanding brain development, organization, and function. Since the earliest days of embryology, lineage questions have been addressed with methods of increasing specificity, capacity, and resolution. Yet, a full realization of individual cell lineages remains challenging for complex systems. A recent explosion of technical advances in genome-editing and single-cell sequencing has enabled lineage analysis in an unprecedented scale, speed, and depth across different species. In this review, we discuss the application of available as well as future genetic labeling techniques for tracking neural lineages in vivo in the mammalian nervous system.
June 2018
Proximity labeling: spatially resolved proteomic mapping for neurobiology
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Shuo Han, Jiefu Li, Alice Y Ting Understanding signaling pathways in neuroscience requires high-resolution maps of the underlying protein networks. Proximity-dependent biotinylation with engineered enzymes, in combination with mass spectrometry-based quantitative proteomics, has emerged as a powerful method to dissect molecular interactions and the localizations of endogenous proteins. Recent applications to neuroscience have provided insights into the composition of sub-synaptic structures, including the synaptic cleft and inhibitory post-synaptic density. Here we compare the different enzymes and small-molecule probes for proximity labeling in the context of cultured neurons and tissue, review existing studies, and provide technical suggestions for the in vivo application of proximity labeling.
June 2018
Genetic strategies to tackle neurological diseases in fruit flies
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): M
June 2018
Mesh electronics: a new paradigm for tissue-like brain probes
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Guosong Hong, Xiao Yang, Tao Zhou, Charles M Lieber Existing implantable neurotechnologies for understanding the brain and treating neurological diseases have intrinsic properties that have limited their capability to achieve chronically-stable brain interfaces with single-neuron spatiotemporal resolution. These limitations reflect what has been dichotomy between the structure and mechanical properties of living brain tissue and non-living neural probes. To bridge the gap between neural and electronic networks, we have introduced the new concept of mesh electronics probes designed with structural and mechanical properties such that the implant begins to ‘look and behave’ like neural tissue. Syringe-implanted mesh electronics have led to the realization of probes that are neuro-attractive and free of the chronic immune response, as well as capable of stable long-term mapping and modulation of brain activity at the single-neuron level. This review provides a historical overview of a 10-year development of mesh electronics by highlighting the tissue-like design, syringe-assisted delivery, seamless neural tissue integration, and single-neuron level chronic recording stability of mesh electronics. We also offer insights on unique near-term opportunities and future directions for neuroscience and neurology that now are available or expected for mesh electronics neurotechnologies.
June 2018
Implantable, wireless device platforms for neuroscience research
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Philipp Gutruf, John A Rogers Recently developed classes of ultraminiaturized wireless devices provide powerful capabilities in neuroscience research, as implantable light sources for simulation/inhibition via optogenetics, as integrated microfluidic systems for programmed pharmacological delivery and as multimodal sensors for physiological measurements. These platforms leverage basic advances in biocompatible materials, semiconductor device designs and systems engineering concepts to afford modes of operation that are qualitatively distinct from those of conventional approaches that tether animals to external hardware by means of optical fibers, electrical cables and/or fluidic tubing. Neuroscience studies that exploit the unique features of these technologies enable insights into neural function through targeted stimulation, inhibition and recording, with spatially and genetically precise manipulation of neural circuit activity. Experimental possibilities include studies in naturalistic, three dimensional environments, investigations of pair-wise or group related social interactions and many other scenarios of interest that cannot be addressed using traditional hardware.
June 2018
Nanomaterials at the neural interface
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Denis Scaini, Laura Ballerini Interfacing the nervous system with devices able to efficiently record or modulate the electrical activity of neuronal cells represents the underlying foundation of future theranostic applications in neurology and of current openings in neuroscience research. These devices, usually sensing cell activity via microelectrodes, should be characterized by safe working conditions in the biological milieu together with a well-controlled operation-life. The stable device/neuronal electrical coupling at the interface requires tight interactions between the electrode surface and the cell membrane. This neuro-electrode hybrid represents the hyphen between the soft nature of neural tissue, generating electrical signals via ion motions, and the rigid realm of microelectronics and medical devices, dealing with electrons in motion. Efficient integration of these entities is essential for monitoring, analyzing and controlling neuronal signaling but poses significant technological challenges. Improving the cell/electrode interaction and thus the interface performance requires novel engineering of (nano)materials: tuning at the nanoscale electrode's properties may lead to engineer interfacing probes that better camouflaged with their biological target. In this brief review, we highlight the most recent concepts in nanotechnologies and nanomaterials that might help reducing the mismatch between tissue and electrode, focusing on the device's mechanical properties and its biological integration with the tissue.
June 2018
Expansion microscopy: development and neuroscience applications
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Emmanouil D Karagiannis, Edward S Boyden Many neuroscience questions center around understanding how the molecules and wiring in neural circuits mechanistically yield behavioral functions, or go awry in disease states. However, mapping the molecules and wiring of neurons across the large scales of neural circuits has posed a great challenge. We recently developed expansion microscopy (ExM), a process in which we physically magnify biological specimens such as brain circuits. We synthesize throughout preserved brain specimens a dense, even mesh of a swellable polymer such as sodium polyacrylate, anchoring key biomolecules such as proteins and nucleic acids to the polymer. After mechanical homogenization of the specimen-polymer composite, we add water, and the polymer swells, pulling biomolecules apart. Due to the larger separation between molecules, ordinary microscopes can then perform nanoscale resolution imaging. We here review the ExM technology as well as applications to the mapping of synapses, cells, and circuits, including deployment in species such as Drosophila, mouse, non-human primate, and human.
June 2018
Recent advances in neural dust: towards a neural interface platform
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Ryan M Neely, David K Piech, Samantha R Santacruz, Michel M Maharbiz, Jose M Carmena The neural dust platform uses ultrasonic power and communication to enable a scalable, wireless, and batteryless system for interfacing with the nervous system. Ultrasound offers several advantages over alternative wireless approaches, including a safe method for powering and communicating with sub mm-sized devices implanted deep in tissue. Early studies demonstrated that neural dust motes could wirelessly transmit high-fidelity electrophysiological data in vivo, and that theoretically, this system could be miniaturized well below the mm-scale. Future developments are focused on further minimization of the platform, better encapsulation methods as a path towards truly chronic neural interfaces, improved delivery mechanisms, stimulation capabilities, and finally refinements to enable deployment of neural dust in the central nervous system.
June 2018
Integrated optoelectronic microprobes
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): L Rudmann, MT Alt, D Ashouri Vajari, T Stieglitz Optogenetics opened not only new exciting opportunities to interrogate the nervous system but also requires adequate probes to facilitate these wishes. Therefore, a multidisciplinary effort is essential to match these technical opportunities with biological needs in order to establish a stable and functional material-tissue interface. This in turn can address an optical intervention of the genetically modified, light sensitive cells in the nervous system and recording of electrical signals from single cells and neuronal networks that result in behavioral changes. In this review, we present the state of the art of optoelectronic probes and assess advantages and challenges of the different design approaches. At first, we discuss mechanisms and processes at the material-tissue interface that influence the performance of optoelectronic probes in acute and chronic implantations. We classify optoelectronic probes by their property of delivering light to the tissue: by waveguides or by integrated light sources at the sites of intervention. Both approaches are discussed with respect to size, spatial resolution, opportunity to integrate electrodes for electrical recording and potential interactions with the target tissue. At last, we assess translational aspects of the state of the art. Long-term stability of probes and the opportunity to integrate them into fully implantable, wireless systems are a prerequisite for chronic applications and a transfer from fundamental neuroscientific studies into treatment options for diseases and clinical trials.
June 2018
Adaptive optical microscopy for neurobiology
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Cristina Rodr
June 2018
Challenges and opportunities for large-scale electrophysiology with Neuropixels probes
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Nicholas A Steinmetz, Christof Koch, Kenneth D Harris, Matteo Carandini Electrophysiological methods are the gold standard in neuroscience because they reveal the activity of individual neurons at high temporal resolution and in arbitrary brain locations. Microelectrode arrays based on complementary metal-oxide semiconductor (CMOS) technology, such as Neuropixels probes, look set to transform these methods. Neuropixels probes provide
June 2018
Synthetic and genetically encoded fluorescent neural activity indicators
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Claire Deo, Luke D Lavis The ultimate goal of neuroscience is to relate the complex activity of cells and cell-networks to behavior and cognition. This requires tools and techniques to visualize neuronal activity. Fluorescence microscopy is an ideal tool to measure activity of cells in the brain due to the high sensitivity of the technique and the growing portfolio of optical hardware and fluorescent sensors. Here, we give a chemist's perspective on the recent progress of fluorescent activity indicators that enable the measurement of cellular events in the living brain. We discuss advances in both chemical and genetically encoded sensors and look forward to hybrid indicators, which incorporate synthetic organic dyes into genetically encoded protein constructs.
April 2018
Toward true closed-loop neuromodulation: artifact-free recording during stimulation
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Andy Zhou, Benjamin C Johnson, Rikky Muller Closed-loop and responsive neuromodulation systems improve open-loop neurostimulation by responding directly to measured neural activity and providing adaptive, on-demand therapy. To be effective, these systems must be able to simultaneously record and stimulate neural activity, a task made difficult by persistent stimulation artifacts that distort and obscure underlying biomarkers. To enable simultaneous stimulation and recording, several techniques have been proposed. These techniques involve artifact-preventing system configurations, resilient recording front-ends, and back-end signal processing for removing recorded artifacts. Co-designing and integrating these artifact cancellation techniques will be key to enabling neuromodulation systems to stimulate and record at the same time. Here, we review the state-of-the-art for these techniques and their role in achieving artifact-free neuromodulation.
April 2018
Model-based predictions for dopamine
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Angela J Langdon, Melissa J Sharpe, Geoffrey Schoenbaum, Yael Niv Phasic dopamine responses are thought to encode a prediction-error signal consistent with model-free reinforcement learning theories. However, a number of recent findings highlight the influence of model-based computations on dopamine responses, and suggest that dopamine prediction errors reflect more dimensions of an expected outcome than scalar reward value. Here, we review a selection of these recent results and discuss the implications and complications of model-based predictions for computational theories of dopamine and learning.
April 2018
Contextual modulation of sound processing in the auditory cortex
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): C Angeloni, MN Geffen In everyday acoustic environments, we navigate through a maze of sounds that possess a complex spectrotemporal structure, spanning many frequencies and exhibiting temporal modulations that differ within frequency bands. Our auditory system needs to efficiently encode the same sounds in a variety of different contexts, while preserving the ability to separate complex sounds within an acoustic scene. Recent work in auditory neuroscience has made substantial progress in studying how sounds are represented in the auditory system under different contexts, demonstrating that auditory processing of seemingly simple acoustic features, such as frequency and time, is highly dependent on co-occurring acoustic and behavioral stimuli. Through a combination of electrophysiological recordings, computational analysis and behavioral techniques, recent research identified the interactions between external spectral and temporal context of stimuli, as well as the internal behavioral state.
April 2018
Gating of visual processing by physiological need
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Christian R Burgess, Yoav Livneh, Rohan N Ramesh, Mark L Andermann Physiological need states and associated motivational drives can bias visual processing of cues that help meet these needs. Human neuroimaging studies consistently show a hunger-dependent, selective enhancement of responses to images of food in association cortex and amygdala. More recently, cellular-resolution imaging combined with circuit mapping experiments in behaving mice have revealed underlying neuronal population dynamics and enabled tracing of pathways by which hunger circuits influence the assignment of value to visual objects in visual association cortex, insular cortex, and amygdala. These experiments begin to provide a mechanistic understanding of motivation-specific neural processing of need-relevant cues in healthy humans and in disease states such as obesity and other eating disorders.
April 2018
Linking dynamic patterns of neural activity in orbitofrontal cortex with decision making
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Erin L Rich, Frederic M Stoll, Peter H Rudebeck Humans and animals demonstrate extraordinary flexibility in choice behavior, particularly when deciding based on subjective preferences. We evaluate options on different scales, deliberate, and often change our minds. Little is known about the neural mechanisms that underlie these dynamic aspects of decision-making, although neural activity in orbitofrontal cortex (OFC) likely plays a central role. Recent evidence from studies in macaques shows that attention modulates value responses in OFC, and that ensembles of OFC neurons dynamically signal different options during choices. When contexts change, these ensembles flexibly remap to encode the new task. Determining how these dynamic patterns emerge and relate to choices will inform models of decision-making and OFC function.
April 2018
Neural mechanisms of movement planning: motor cortex and beyond
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Karel Svoboda, Nuo Li Neurons in motor cortex and connected brain regions fire in anticipation of specific movements, long before movement occurs. This neural activity reflects internal processes by which the brain plans and executes volitional movements. The study of motor planning offers an opportunity to understand how the structure and dynamics of neural circuits support persistent internal states and how these states influence behavior. Recent advances in large-scale neural recordings are beginning to decipher the relationship of the dynamics of populations of neurons during motor planning and movements. New behavioral tasks in rodents, together with quantified perturbations, link dynamics in specific nodes of neural circuits to behavior. These studies reveal a neural network distributed across multiple brain regions that collectively supports motor planning. We review recent advances and highlight areas where further work is needed to achieve a deeper understanding of the mechanisms underlying motor planning and related cognitive processes.
April 2018
Decision-making behaviors: weighing ethology, complexity, and sensorimotor compatibility
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Ashley L Juavinett, Jeffrey C Erlich, Anne K Churchland Rodent decision-making research aims to uncover the neural circuitry underlying the ability to evaluate alternatives and select appropriate actions. Designing behavioral paradigms that provide a solid foundation to ask questions about decision-making computations and mechanisms is a difficult and often underestimated challenge. Here, we propose three dimensions on which we can consider rodent decision-making tasks: ethological validity, task complexity, and stimulus-response compatibility. We review recent research through this lens, and provide practical guidance for researchers in the decision-making field.
April 2018
Do the right thing: neural network mechanisms of memory formation, expression and update in Drosophila
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Paola Cognigni, Johannes Felsenberg, Scott Waddell When animals learn, plasticity in brain networks that respond to specific cues results in a change in the behavior that these cues elicit. Individual network components in the mushroom bodies of the fruit fly Drosophila melanogaster represent cues, learning signals and behavioral outcomes of learned experience. Recent findings have highlighted the importance of dopamine-driven plasticity and activity in feedback and feedforward connections, between various elements of the mushroom body neural network. These computational motifs have been shown to be crucial for long term olfactory memory consolidation, integration of internal states, re-evaluation and updating of learned information. The often recurrent circuit anatomy and a prolonged requirement for activity in parts of these underlying networks, suggest that self-sustained and precisely timed activity is a fundamental feature of network computations in the insect brain. Together these processes allow flies to continuously adjust the content of their learned knowledge and direct their behavior in a way that best represents learned expectations and serves their most pressing current needs.
April 2018
Building a state space for song learning
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Emily Lambert Mackevicius, Michale Sean Fee The songbird system has shed light on how the brain produces precisely timed behavioral sequences, and how the brain implements reinforcement learning (RL). RL is a powerful strategy for learning what action to produce in each state, but requires a unique representation of the states involved in the task. Songbird RL circuitry is thought to operate using a representation of each moment within song syllables, consistent with the sparse sequential bursting of neurons in premotor cortical nucleus HVC. However, such sparse sequences are not present in very young birds, which sing highly variable syllables of random lengths. Here, we review and expand upon a model for how the songbird brain could construct latent sequences to support RL, in light of new data elucidating connections between HVC and auditory cortical areas. We hypothesize that learning occurs via four distinct plasticity processes: 1) formation of ‘tutor memory’ sequences in auditory areas; 2) formation of appropriately-timed latent HVC sequences, seeded by inputs from auditory areas spontaneously replaying the tutor song; 3) strengthening, during spontaneous replay, of connections from HVC to auditory neurons of corresponding timing in the ‘tutor memory’ sequence, aligning auditory and motor representations for subsequent song evaluation; and 4) strengthening of connections from premotor neurons to motor output neurons that produce the desired sounds, via well-described song RL circuitry.
April 2018
Mutual inhibition of lateral inhibition: a network motif for an elementary computation in the brain
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Minoru Koyama, Avinash Pujala A series of classical studies in non-human primates has revealed the neuronal activity patterns underlying decision-making. However, the circuit mechanisms for such patterns remain largely unknown. Recent detailed circuit analyses in simpler neural systems have started to reveal the connectivity patterns underlying analogous processes. Here we review a few of these systems that share a particular connectivity pattern, namely mutual inhibition of lateral inhibition. Close examination of these systems suggests that this recurring connectivity pattern (‘network motif’) is a building block to enforce particular dynamics, which can be used not only for simple behavioral choice but also for more complex choices and other brain functions. Thus, a network motif provides an elementary computation that is not specific to a particular brain function and serves as an elementary building block in the brain.
April 2018
A disinhibitory circuit motif and flexible information routing in the brain
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Xiao-Jing Wang, Guangyu Robert Yang In the mammalian neocortex, an area typically receives inputs from, and projects to, dozens of other areas. Mechanisms are needed to flexibly route information to the right place at the right time, which we term ‘pathway gating’. For instance, a region in your brain that receives signals from both visual and auditory pathways may want to ‘gate in’ the visual pathway while ‘gating out’ the auditory pathway when you try to read a book surrounded by people in a noisy caf
April 2018
The promise and perils of causal circuit manipulations
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Steffen BE Wolff, Bence P
April 2018
Sex differences in behavioral strategies: avoiding interpretational pitfalls
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Rebecca M Shansky Despite ample evidence for sex differences in brain structure and function, our understanding of the neurobiological basis of behavior comes almost exclusively from male animals. As neuroscientists move to comply with recent NIH mandates that biomedical researchers include both sexes in their studies, the ways we interpret outcomes in classic rodent behavioral models deserve closer scrutiny and more nuanced evaluation. In this mini-review, we highlight recent sex differences papers in learning, decision-making, and spatial navigation paradigms that underscore the distinctions between cognitive capabilities versus behavioral strategies that may confer unique benefits to males and females.
April 2018
Advances in understanding neural mechanisms of social dominance
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Tingting Zhou, Carmen Sandi, Hailan Hu Dominance hierarchy profoundly impacts social animals’ survival, physical and mental health and reproductive success. As the measurements of dominance hierarchy in rodents become established, it is now possible to understand the neural mechanism mediating the intrinsic and extrinsic factors determining social hierarchy. This review summarizes the latest advances in assay development for measuring dominance hierarchy in laboratory mice. It also reviews our current understandings on how activity and plasticity of specific neural circuits shape the dominance trait and mediate the ‘winner effect’.
February 2018
Mixed selectivity encoding and action selection in the prefrontal cortex during threat assessment
Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49 Author(s): Itamar S Grunfeld, Ekaterina Likhtik The medial prefrontal cortex (mPFC) regulates expression of emotional behavior. The mPFC combines multivariate information from its inputs, and depending on the imminence of threat, activates downstream networks that either increase or decrease the expression of anxiety-related motor behavior and autonomic activation. Here, we selectively highlight how subcortical input to the mPFC from two example structures, the amygdala and ventral hippocampus, help shape mixed selectivity encoding and action selection during emotional processing. We outline a model where prefrontal subregions modulate behavior along orthogonal motor dimensions, and exhibit connectivity that selects for expression of one behavioral strategy while inhibiting the other.
February 2018
Editorial Board
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48

February 2018
Contents page
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48

February 2018
Editorial overview: Neurobiology of disease (2018)
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Claudia Bagni, Anatol C Kreitzer
February 2018
Neurobiology of autoimmune encephalitis
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Masaki Fukata, Norihiko Yokoi, Yuko Fukata Autoimmune encephalitis presenting with amnesia, seizures, and psychosis is highly topical in basic and clinical neuroscience. Recent studies have identified numerous associated autoantibodies, targeting cell-surface synaptic proteins including neurotransmitter receptors (e.g. NMDA receptors (NMDARs)) and a secreted protein, LGI1. In vitro and in vivo analyses of the influence of the autoantibodies have begun to clarify their causal roles. Of particular interest is the generation of recombinant monoclonal antibodies from patients’ B cells with anti-NMDAR encephalitis. Patient monoclonal antibodies could be useful to reveal their direct, detailed pathogenicity. Such identification and characterization of autoantibodies could create new categories of neurological diseases and promote the understanding of patho-physiologic roles of target proteins in human brain function.
February 2018
Striatal synapses, circuits, and Parkinson's disease
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Shenyu Zhai, Asami Tanimura, Steven M Graves, Weixing Shen, D James Surmeier The striatum is a hub in the basal ganglia circuitry controlling goal directed actions and habits. The loss of its dopaminergic (DAergic) innervation in Parkinson's disease (PD) disrupts the ability of the two principal striatal projection systems to respond appropriately to cortical and thalamic signals, resulting in the hypokinetic features of the disease. New tools to study brain circuitry have led to significant advances in our understanding of striatal circuits and how they adapt in PD models. This short review summarizes some of these recent studies and the gaps that remain to be filled.
February 2018
Dopaminergic dysfunction in neurodevelopmental disorders: recent advances and synergistic technologies to aid basic research
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): J Elliott Robinson, Viviana Gradinaru Neurodevelopmental disorders (NDDs) represent a diverse group of syndromes characterized by abnormal development of the central nervous system and whose symptomatology includes cognitive, emotional, sensory, and motor impairments. The identification of causative genetic defects has allowed for creation of transgenic NDD mouse models that have revealed pathophysiological mechanisms of disease phenotypes in a neural circuit- and cell type-specific manner. Mouse models of several syndromes, including Rett syndrome, Fragile X syndrome, Angelman syndrome, Neurofibromatosis type 1, etc., exhibit abnormalities in the structure and function of dopaminergic circuitry, which regulates motivation, motor behavior, sociability, attention, and executive function. Recent advances in technologies for functional circuit mapping, including tissue clearing, viral vector-based tracing methods, and optical readouts of neural activity, have refined our knowledge of dopaminergic circuits in unperturbed states, yet these tools have not been widely applied to NDD research. Here, we will review recent findings exploring dopaminergic function in NDD models and discuss the promise of new tools to probe NDD pathophysiology in these circuits.

Graphical abstract

image
February 2018
Deciphering MECP2-associated disorders: disrupted circuits and the hope for repair
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Zilong Qiu MECP2 is a critical gene for neural development, mutations or duplication of which led to severe neurodevelopmental disorders, such as Rett syndrome (RTT) and autism spectrum disorders (ASD). Extensive works during the past decade yield ample insights into the molecular and cellular functions of MeCP2 in neural development. Furthermore, genetic manipulations in Mecp2 mouse models strongly suggested that deficiency in synaptic plasticity and various behaviors of Mecp2 null or transgenic mice could be rescued in adulthood. Further studies elucidating neural circuits responsible for symptoms in MECP2-associated disorders in rodent and non-human primate models will shed light on the development of potential therapeutic interventions.
February 2018
Dysregulation of aversive signaling pathways: a novel circuit endophenotype for pain and anxiety disorders
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Li-Feng Yeh, Mayumi Watanabe, Jessica Sulkes-Cuevas, Joshua P Johansen Aversive experiences activate dedicated neural instructive pathways which trigger memory formation and change behavior. The strength of these aversive memories and the degree to which they alter behavior is proportional to the intensity of the aversive experience. Dysregulation of aversive learning circuits can lead to psychiatric pathology. Here we review recent findings elucidating aversive instructive signaling circuits for fear conditioning. We then examine how chronic pain as well as stress and anxiety disrupt these circuits and the implications this has for understanding and treating psychiatric disease. Together this review synthesizes current work on aversive instructive signaling circuits in health and disease and suggests a novel circuit based framework for understanding pain and anxiety syndromes.
February 2018
Closing gaps in brain disease—from overlapping genetic architecture to common motifs of synapse dysfunction
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Jochen Roeper Recent progress in the synaptic pathophysiology of brain diseases is reviewed. To emphasize the emergence of common motifs in synapse dysfunctions across neurodevelopmental, psychiatric and neurological disorders, conventional clinical boundaries are disregarded and a decidedly trans-diagnostic, potentially unifying view of altered synapse function is promoted. Based on the overlapping genetic architecture of brain disorders, which often converges on genes related to synaptic functions, disease-related changes in basic pre-synaptic and post-synaptic communication, neuromodulation-gated changes in Hebbian plasticity, dynamic interactions between Hebbian and homeostatic plasticity, and changes in synaptic maintenance by autophagy and glial-mediated phagocytosis are highlighted.
February 2018
Endo-lysosomal dysfunction: a converging mechanism in neurodegenerative diseases
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Chao Wang, Maria A Telpoukhovskaia, Ben A Bahr, Xu Chen, Li Gan Endo-lysosomal pathways are essential in maintaining protein homeostasis in the cell. Numerous genes in the endo-lysosomal pathways have been found to associate with neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and frontotemporal dementia (FTD). Mutations of these genes lead to dysfunction in multiple steps of the endo-lysosomal network: autophagy, endocytic trafficking and lysosomal degradation, resulting in accumulation of pathogenic proteins. Although the exact pathogenic mechanism varies for different disease-associated genes, dysfunction of the endo-lysosomal pathways represents a converging mechanism shared by these diseases. Therefore, strategies that correct or compensate for endo-lysosomal dysfunction may be promising therapeutic approaches to treat neurodegenerative diseases.
February 2018
Windows of opportunity: timing in neurodevelopmental disorders
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Alexandra Krol, Guoping Feng Developmental processes disrupted in neurodevelopmental disorders occur rapidly and with temporal precision. During development, individual gene activity can dynamically engage different signaling networks; thus genetic mutations can lead to different functional changes at different times. Interpretation of phenotypes can be further complicated if initial functional changes trigger compensatory mechanisms. Examining genetic mouse models of neurodevelopmental disorders reveals cellular phenotypes that change over the course of development and exist long before behavioral deficits are assessed. Correspondingly, earlier genetic interventions in these disorder models have often been more effective at improving behavioral deficits than late interventions. The restricted period of effective intervention demonstrates that identifying a target window is an essential component of treatment.
February 2018
Decoding hidden messages in neurons: insights from epitranscriptome-controlled and specialized ribosome-controlled translation
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Yi-Shuian Huang, Wen-Hsin Lu Activity-regulated protein synthesis, especially in the restricted synaptic domains, is critical to maintaining connections and communication between neurons. Accumulating evidence has linked dysregulated translation to various neurodevelopmental or neurodegenerative diseases. In the past 3 decades, after finding ribosomes and specific mRNAs localized around synapses, a significant amount of work has furthered our understanding of how the genetic sequences in mRNAs and their cognate RNA-binding proteins are coordinated to build up synaptic proteomes. Recent exciting findings of various RNA modifications, specialized ribosomes, and their regulatory roles in translation have led to emerging needs to unravel how synaptic ribosomes interpret these hidden codes to regulate molecular connectomes.
February 2018
Synaptic plasticity may underlie l-DOPA induced dyskinesia
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Anders Borgkvist, Ori J Lieberman, David Sulzer l-DOPA provides highly effective treatment for Parkinson's disease, but l-DOPA induced dyskinesia (LID) is a very debilitating response that eventually is presented by a majority of patients. A central issue in understanding the basis of LID is whether it is due to a response to chronic l-DOPA over years of therapy, and/or due to synaptic changes that follow the loss of dopaminergic neurotransmission and then triggered by acute l-DOPA administration. We review recent work that suggests that specific synaptic changes in the D1 dopamine receptor-expressing direct pathway striatal projection neurons due to loss of dopamine in Parkinson's disease are responsible for LID. Chronic l-DOPA may nevertheless modulate LID through priming mechanisms.
February 2018
Molecular insights into cortico-striatal miscommunications in Huntington's disease
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Matthew B Veldman, X William Yang Huntington's disease (HD), a dominantly inherited neurodegenerative disease, is defined by its genetic cause, a CAG-repeat expansion in the HTT gene, its motor and psychiatric symptomology and primary loss of striatal medium spiny neurons (MSNs). However, the molecular mechanisms from genetic lesion to disease phenotype remain largely unclear. Mouse models of HD have been created that exhibit phenotypes partially recapitulating those in the patient, and specifically, cortico-striatal disconnectivity appears to be a shared pathogenic event shared by HD mouse models and patients. Molecular studies have begun to unveil converging molecular and cellular pathogenic mechanisms that may account for cortico-striatal miscommunication in various HD mouse models. Systems biological approaches help to illuminate synaptic molecular networks as a nexus for HD cortio-striatal pathogenesis, and may offer new candidate targets to modify the disease.
February 2018
Lateral habenula in the pathophysiology of depression
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Yan Yang, Hao Wang, Ji Hu, Hailan Hu Depression is a devastating disorder with a combination of diverse symptoms such as low self-esteem, lack of motivation, anhedonia, loss of appetite, low energy, and discomfort without a clear cause. Depression has been suggested to be the result of maladaptive changes in specific brain circuits. Recently, the lateral habenula (LHb) has emerged as a key brain region in the pathophysiology of depression. Increasing evidence from rodent, non-human primate and human studies indicates that the aberrant activity of the LHb is associated with depressive symptoms such as helplessness, anhedonia, and excessive negative focus. Revealing the molecular, cellular and circuit properties of the LHb will help explain how abnormalities in LHb activity are linked to depressive disorders, and shed light on developing novel strategies for depression treatment.
February 2018
Building stereotypic connectivity: mechanistic insights into structural plasticity from C. elegans
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Yishi Jin, Yingchuan B Qi The ability of neurons to modify or remodel their synaptic connectivity is critical for the function of neural circuitry throughout the life of an animal. Understanding the mechanisms underlying neuronal structural changes is central to our knowledge of how the nervous system is shaped for complex behaviors and how it further adapts to developmental and environmental demands. Caenorhabditis elegans provides a powerful model for examining developmental processes and for discovering mechanisms controlling neural plasticity. Recent findings have identified conserved themes underlying neural plasticity in development and under environmental stress.
February 2018
Disrupted circuits in mouse models of autism spectrum disorder and intellectual disability
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Carla EM Golden, Joseph D Buxbaum, Silvia De Rubeis Autism spectrum disorder (ASD) and intellectual disability (ID) are caused by a wide range of genetic mutations, a significant fraction of which reside in genes important for synaptic function. Studies have found that sensory, prefrontal, hippocampal, cerebellar, and striatal regions, as well as the circuits that connect them, are perturbed in mouse models of ASD and ID. Dissecting the disruptions in morphology and activity in these neural circuits might help us to understand the shared risk between the two disorders as well as their clinical heterogeneity. Treatments that target the balance between excitation and inhibition in these regions are able to reverse pathological phenotypes, elucidating this deficit as a commonality across models and opening new avenues for intervention.
February 2018
Autophagy and proteostasis in the control of synapse aging and disease
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): YongTian Liang, Stephan Sigrist The maintenance of neuronal homeostasis is severely threatened by aging, probably partially due to compromised autophagic clearance. Hence, rejuvenating autophagy in aging neurons is considered a promising strategy to restore cognitive performance. Research in recent years has shown that autophagosome biogenesis takes place mainly in distal axons and, thus, close to presynaptic specializations, and that efficient macro-autophagy is essential for neuronal homeostasis and survival. Retrograde transport of autophagosomes might play a role in neuronal signaling processes, promoting neuronal complexity and preventing neurodegeneration. Here, we discuss recent advances concerning the intersection of aging, neurodegeneration and autophagy, and try to create a unified view of how neuronal autophagy and proteostasis might control synaptic aging and disease.

NLGN1 and NLGN2 in the prefrontal cortex: their role in memory consolidation and strengthening
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48 Author(s): Aaron Katzman, Cristina M Alberini The prefrontal cortex (PFC) is critical for memory formation, but the underlying molecular mechanisms are poorly understood. Clinical and animal model studies have shown that changes in PFC excitation and inhibition are important for cognitive functions as well as related disorders. Here, we discuss recent findings revealing the roles of the excitatory and inhibitory synaptic proteins neuroligin 1 (NLGN1) and NLGN2 in the PFC in memory formation and modulation of memory strength. We propose that shifts in NLGN1 and NLGN2 expression in specific excitatory and inhibitory neuronal subpopulations in response to experience regulate the dynamic processes of memory consolidation and strengthening. Because excitatory/inhibitory imbalances accompany neuropsychiatric disorders in which strength and flexibility of representations play important roles, understanding these mechanisms may suggest novel therapies.
view: 207

Summer Sale: Free Shipping + 6% OFF on Orders Over $25 with Coupon

Code: VS06

Start: 11 Jul 2017 | End: 31 Mar 2018

(US) Dynamite Studio - Join the Loyalty Program and Receive 30% off 1 Regular Price Item on Your Birthday!

Start: 17 Aug 2017 | End: 01 May 2018

$1 OFF $10, $2 OFF $19, offer valid until 04/30/2018.

Code: SHOPTD1

Start: 29 Oct 2017 | End: 30 Apr 2018

Search All Amazon* UK* DE* FR* JP* CA* CN* IT* ES* IN* BR* MX
Booking.com B.V. is based in Amsterdam in the Netherlands. Ready for some statistics? Our 1,534,024 properties, including 860,482 holiday rentals, are located in 123,105 destinations in 229 countries and territories, and are supported internationally by 198 offices in 70 countries.
2013 Copyright © Techhap.com Mobile version 2015 | PeterLife & company
Terms of use Link at is mandatory if site materials are using fully or particulary.
Were treated to the site administrator, a cup of coffee *https://paypal.me/peterlife
Yandex.ru