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Current Opinion in Neurobiology

Meng Liu, Carlos Blanco-Centurion, Priyattam J Shiromani
Narcolepsy was first identified almost 130 years ago, but it was only 15 years ago that it was identified as a neurodegenerative disease linked to a loss of orexin neurons in the brain. It is unclear what causes the orexin neurons to die, but our strategy has been to place the gene for orexin into surrogate neurons in the validated mouse models of narcolepsy, and test whether it can block narcolepsy symptoms, such as cataplexy. In both the orexin knockout and the orexin-ataxin-3 mouse models of narcolepsy we have found that cataplexy can be blocked if the surrogate neurons are part of the circuit responsible for cataplexy...
April 23, 2017: Current Opinion in Neurobiology
Barbara E Jones
Electrophysiological recordings indicate that neurons which discharge maximally in association with distinct sleep-wake states are distributed through the brain, albeit in differing proportions. As studied using juxtacellular recording and labeling within the basal forebrain, four functional principal cell types are distinguished as: wake/paradoxical sleep (W/PS)-, slow wave sleep (SWS)-, W- and PS-max active. They are each comprised by both GABA and glutamate neurons, in addition to acetylcholine neurons belonging to the W/PS group...
April 19, 2017: Current Opinion in Neurobiology
Friedemann Zenke, Wulfram Gerstner, Surya Ganguli
Hebbian plasticity, a synaptic mechanism which detects and amplifies co-activity between neurons, is considered a key ingredient underlying learning and memory in the brain. However, Hebbian plasticity alone is unstable, leading to runaway neuronal activity, and therefore requires stabilization by additional compensatory processes. Traditionally, a diversity of homeostatic plasticity phenomena found in neural circuits is thought to play this role. However, recent modelling work suggests that the slow evolution of homeostatic plasticity, as observed in experiments, is insufficient to prevent instabilities originating from Hebbian plasticity...
April 18, 2017: Current Opinion in Neurobiology
Tim P Vogels, Leslie C Griffith
No abstract text is available yet for this article.
April 17, 2017: Current Opinion in Neurobiology
Takayuki Yamashita, Akihiro Yamanaka
The lateral hypothalamic area (LHA) of the diencephalon is crucially involved in controlling instinctive behavior such as sleep-wake cycle and feeding behavior. LHA is a heterogeneous structure that contains spatially intermingled, genetically distinct cell populations. Among LHA neurons, orexin/hypocretin (OX) neuron is the key cell type that promotes waking, and specific loss of OX neurons results in narcolepsy. Melanin-concentrating hormone (MCH) containing neurons are known to be active during rapid eye movement (REM) sleep and stimulation of these neurons promotes REM sleep...
April 17, 2017: Current Opinion in Neurobiology
Tobias Kaiser, Yang Zhou, Guoping Feng
Monogenic animal models for psychiatric diseases have enabled researchers to dissect the relationship between certain candidate genes, neural circuit abnormalities, and behavioral phenotypes along development. Early reports of phenotypic reversal after genetic restoration in mouse models sparked hope that genetic defects do not damage circuits irreversibly in early-onset disorders. However, further studies have suggested that only some circuits exhibit this plasticity, while many others require proper gene function during development...
April 15, 2017: Current Opinion in Neurobiology
Talia Levitas-Djerbi, Lior Appelbaum
What are the molecular and cellular mechanisms that link neurological disorders and sleep disturbances? The transparent zebrafish model could bridge this gap in knowledge due to its unique genetic and imaging toolbox, and amenability to high-throughput screening. Sleep is well-characterized in zebrafish and key regulators of the sleep/wake cycle are conserved, including melatonin and hypocretin/orexin (Hcrt), whereas novel sleep regulating proteins are continually being identified, such as Kcnh4a, Neuromedin U, and QRFP...
April 14, 2017: Current Opinion in Neurobiology
Richard H Roth, Yong Zhang, Richard L Huganir
Modulation of synaptic strength through trafficking of AMPA receptors is a fundamental mechanism underlying synaptic plasticity and has been shown to be an important process in higher brain functions such as learning and memory. Many studies have used live time-lapse imaging of fluorescently tagged AMPA receptors to directly monitor their membrane trafficking in the basal state as well as during synaptic plasticity. While most of these studies are performed in vitro using neuronal cell cultures, in the past years technological advances have enabled the imaging of synaptic proteins in vivo in intact organisms...
April 12, 2017: Current Opinion in Neurobiology
Renato Duarte, Alexander Seeholzer, Karl Zilles, Abigail Morrison
Neocortical circuits, as large heterogeneous recurrent networks, can potentially operate and process signals at multiple timescales, but appear to be differentially tuned to operate within certain temporal receptive windows. The modular and hierarchical organization of this selectivity mirrors anatomical and physiological relations throughout the cortex and is likely determined by the regional electrochemical composition. Being consistently patterned and actively regulated, the expression of molecules involved in synaptic transmission constitutes the most significant source of laminar and regional variability...
April 10, 2017: Current Opinion in Neurobiology
Chiara Cirelli
The synaptic homeostasis hypothesis (SHY) states that wake brings about a net overall increase in synaptic strength in many brain circuits that needs to be renormalized by sleep. I will review recent studies that were either specifically designed to test SHY or were interpreted accordingly, including several experiments that focused on changes in neuronal firing rates. I will emphasize that central to SHY is the idea that what is being regulated across the sleep/wake cycle is synaptic strength, not firing rate, and firing rate taken in isolation is not necessarily an adequate proxy for synaptic strength...
April 8, 2017: Current Opinion in Neurobiology
Simon Jb Butt, Jacqueline A Stacey, Yayoi Teramoto, Cristiana Vagnoni
GABAergic interneurons are a highly heterogeneous group of cells that are critical for the mature function and development of the neocortex. In terms of the latter, much attention has focused on the well-established role of parvalbumin (PV+)-expressing, fast spiking, basket cells in determining the critical period plasticity. However recent endeavours have started to shed the light on the contribution of other interneuron subtypes to early circuit formation and plasticity. Data suggests that there are significant interactions between PV+ cells and other interneuron subtypes that regulate circuit development in rodents in the first postnatal week...
April 8, 2017: Current Opinion in Neurobiology
Grigorios Oikonomou, David A Prober
Sleep consumes a third of our lifespan, but we are far from understanding how it is initiated, maintained and terminated, or what purposes it serves. To address these questions, alternative model systems have recently been recruited. The diurnal zebrafish holds the promise of bridging the gap between simple invertebrate systems, which show little neuroanatomical conservation with mammals, and well-established, but complex and nocturnal, murine systems. Zebrafish larvae can be monitored in a high-throughput fashion, pharmacologically tested by adding compounds into the water, genetically screened using transient transgenesis, and optogenetically manipulated in a non-invasive manner...
April 6, 2017: Current Opinion in Neurobiology
Ida L Barlow, Jason Rihel
All animals have a fundamental and unavoidable requirement for rest, yet we still do not fully understand the processes that initiate, maintain, and regulate sleep. The larval zebrafish is an optically translucent, genetically tractable model organism that exhibits sleep states regulated by conserved sleep circuits, thereby offering a unique system for investigating the genetic and neural control of sleep. Recent studies using high throughput monitoring of larval sleep/wake behaviour have unearthed novel modulators involved in regulating arousal and have provided new mechanistic insights into the role of established sleep/wake modulators...
April 6, 2017: Current Opinion in Neurobiology
Wolfram Schultz, Wiliam R Stauffer, Armin Lak
The phasic dopamine reward prediction error response is a major brain signal underlying learning, approach and decision making. This dopamine response consists of two components that reflect, initially, stimulus detection from physical impact and, subsequenttly, reward valuation; dopamine activations by punishers reflect physical impact rather than aversiveness. The dopamine reward signal is distinct from earlier reported and recently confirmed phasic changes with behavioural activation. Optogenetic activation of dopamine neurones in monkeys causes value learning and biases economic choices...
April 6, 2017: Current Opinion in Neurobiology
Jorge Jaramillo, Richard Kempter
In the hippocampal formation, the sequential activation of place-specific cells represents a conceptual model for the spatio-temporal events that assemble episodic memories. The imprinting of behavioral sequences in hippocampal networks might be achieved via spike-timing-dependent plasticity and phase precession of the spiking activity of neurons. It is unclear, however, whether phase precession plays an active role by enabling sequence learning via synaptic plasticity or whether phase precession passively reflects retrieval dynamics...
April 6, 2017: Current Opinion in Neurobiology
Seil Jang, Hyejin Lee, Eunjoon Kim
Synaptic adhesion molecules have been extensively studied for their contribution to the regulation of synapse development through trans-synaptic adhesions. However, accumulating evidence increasingly indicates that synaptic adhesion molecules are also involved in the regulation of excitatory synaptic transmission and plasticity, often through direct or close associations with excitatory neurotransmitter receptors. This review summarizes recent results supporting this emerging concept and underlying mechanisms, and addresses its implications...
April 6, 2017: Current Opinion in Neurobiology
Randi L Rawson, E Anne Martin, Megan E Williams
For most neurons to function properly, they need to develop synaptic specificity. This requires finding specific partner neurons, building the correct types of synapses, and fine-tuning these synapses in response to neural activity. Synaptic specificity is common at both a neuron's input and output synapses, whereby unique synapses are built depending on the partnering neuron. Neuroscientists have long appreciated the remarkable specificity of neural circuits but identifying molecular mechanisms mediating synaptic specificity has only recently accelerated...
April 4, 2017: Current Opinion in Neurobiology
David Van Vactor, Stephan J Sigrist
Effective adaptation of neural circuit function to a changing environment requires many forms of plasticity. Among these, structural plasticity is one of the most durable, and is also an intrinsic part of the developmental logic for the formation and refinement of synaptic connectivity. Structural plasticity of presynaptic sites can involve the addition, remodeling, or removal of pre- and post-synaptic elements. However, this requires coordination of morphogenesis and assembly of the subcellular machinery for neurotransmitter release within the presynaptic neuron, as well as coordination of these events with the postsynaptic cell...
April 4, 2017: Current Opinion in Neurobiology
Eric Jacobi, Jakob von Engelhardt
AMPA receptor (AMPAR) complexes comprise four of the AMPAR subunits GluA1-4 and several additional interacting proteins. Subunit composition determines AMPAR function. However, AMPAR function depends to a large extent also on interacting proteins, which influence trafficking to the cell surface, activity-dependent subcellular localization and gating of AMPARs. In this review we report about recent findings on the diversity of AMPAR complexes that allow us to better understand functional properties of native receptors in the brain...
April 1, 2017: Current Opinion in Neurobiology
Gregory Artiushin, Amita Sehgal
Sleep is a deeply conserved, yet fundamentally mysterious behavioral state. Knowledge of the circuitry of sleep-wake regulation is an essential step in understanding the physiology of the sleeping brain. Recent efforts in Drosophila have revealed new populations which impact sleep, as well as provided unprecedented mechanistic and electrophysiological detail of established sleep-regulating neurons. Multiple, distributed centers of sleep-wake circuitry exist in the fly, including the mushroom bodies, central complex and the circadian clock cells...
March 30, 2017: Current Opinion in Neurobiology
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