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Current Opinion in Neurobiology

Toru Takumi, Kota Tamada
Copy number variants (CNVs), characterized in recent years by cutting-edge technology, add complexity to our knowledge of the human genome. CNVs contribute not only to human diversity but also to different kinds of diseases including neurodevelopmental delay, autism spectrum disorder and neuropsychiatric diseases. Interestingly, many pathogenic CNVs are shared among these diseases. Studies suggest that pathophysiology of disease may not be simply attributed to a single driver gene within a CNV but also that multifactorial effects may be important...
January 10, 2018: Current Opinion in Neurobiology
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...
January 10, 2018: Current Opinion in Neurobiology
Lujia Zhou, Patrik Verstreken
Recent genome-wide association studies (GWAS) have identified numerous genetic risk variants for late-onset Alzheimer's disease (AD) and Parkinson's disease (PD). However, deciphering the functional consequences of GWAS data is challenging due to a lack of reliable model systems to study the genetic variants that are often of low penetrance and non-coding identities. Pluripotent stem cell (PSC) technologies offer unprecedented opportunities for molecular phenotyping of GWAS variants in human neurons and microglia...
January 10, 2018: Current Opinion in Neurobiology
Isabel Del Pino, Beatriz Rico, Oscar MarĂ­n
Neuropsychiatric disorders arise from the alteration of normal brain developmental trajectories disrupting the function of specific neuronal circuits. Recent advances in human genetics have greatly accelerated the identification of genes whose variation increases the susceptibility for neurodevelopmental disorders, most notably for autism spectrum disorder (ASD) and schizophrenia. In parallel, experimental studies in animal models-most typically in mice-are beginning to shed light on the role of these genes in the development and function of specific brain circuits...
January 9, 2018: Current Opinion in Neurobiology
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...
January 6, 2018: Current Opinion in Neurobiology
Elena Marcello, Monica Di Luca, Fabrizio Gardoni
In the last decade several synaptonuclear protein messengers including Jacob, CRTC1, AIDA-1, ProSaP2/Shank3 and RNF10 have been identified and characterized as key players for modulation of synaptic transmission and synaptic plasticity. Activation of excitatory glutamatergic synapses leads to their shuttling from the synapse to the nucleus, mostly importin-mediated, and subsequent regulation of gene transcription needed for long lasting modifications of synaptic function. Accordingly, increasing evidences show that alterations of the activity of synaptonuclear messengers are correlated to synaptic failure as observed in different synaptopathies...
January 6, 2018: Current Opinion in Neurobiology
Domenico Azarnia Tehran, Marijn Kuijpers, Volker Haucke
Neuronal signaling depends on the exocytic fusion and subsequent endocytic retrieval and reformation of neurotransmitter-containing synaptic vesicles at synapses. Recent findings have uncovered surprising roles of presynaptic endocytic proteins in the formation and transport of autophagosomes. These include functions of the membrane remodelling protein endophilin and its downstream effector, the phosphoinositide phosphatase synaptojanin, in autophagosome formation and in Parkinson's disease, the endocytic sorting adaptor CALM in protein degradation via the autophagy/lysosomal pathway in Alzheimer's disease, and the clathrin adaptor complex AP-2 in retrograde transport of signaling autophagosomes to prevent neurodegeneration...
January 6, 2018: Current Opinion in Neurobiology
Le Xiao, Peter Scheiffele
The view of cerebellar functions has been extended from controlling sensorimotor processes to processing 'contextual' information and generating predictions for a diverse range of behaviors. These functions rely on the computation of the local cerebellar microcircuits and long-range connectivity that relays cerebellar output to various brain areas. In this review, we discuss recent work on two of the circuit elements, which are thought to be fundamental for a wide range of non-sensorimotor behaviors: The role for cerebellar granule cells in multimodal integration in the cerebellar cortex and the long-range connectivity between the deep cerebellar nuclei and the basal ganglia...
January 6, 2018: Current Opinion in Neurobiology
Francesco Petrelli, Paola Bezzi
Astrocytes, the largest glial population in human and murine brains, are crucial to the regulation of synaptic connectivity. During the first three weeks of postnatal development, immature astrocytes express mGlu5 and expands several fold while undergoing a transition towards their mature phase. Although mGlu5-mediated signalling in astrocyte functions has been extensively studied in the last decades, whether this signalling is implicated in the mechanisms governing their development, as well as the effects of dysregulated astrocytic development on neurodevelopmental disorders, are still unclear...
January 6, 2018: Current Opinion in Neurobiology
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...
December 28, 2017: Current Opinion in Neurobiology
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...
December 27, 2017: Current Opinion in Neurobiology
Roberto Sacco, Emanuele Cacci, Gaia Novarino
The precise control of neural stem cell (NSC) proliferation and differentiation is crucial for the development and function of the human brain. Here, we review the emerging links between the alteration of embryonic and adult neurogenesis and the etiology of neuropsychiatric disorders (NPDs) such as autism spectrum disorders (ASDs) and schizophrenia (SCZ), as well as the advances in stem cell-based modeling and the novel therapeutic targets derived from these studies.
December 26, 2017: Current Opinion in Neurobiology
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...
December 23, 2017: Current Opinion in Neurobiology
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...
December 21, 2017: Current Opinion in Neurobiology
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...
December 18, 2017: Current Opinion in Neurobiology
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...
December 16, 2017: Current Opinion in Neurobiology
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...
December 5, 2017: Current Opinion in Neurobiology
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...
December 1, 2017: Current Opinion in Neurobiology
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...
November 25, 2017: Current Opinion in Neurobiology
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...
November 24, 2017: Current Opinion in Neurobiology
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