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TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Δ9-tetrahydrocannabiorcol
TRPA1 is a key ion channel in pain signalling. This study shows that activation of TRPA1 in the spinal cord by acetaminophen metabolites and a non-electrophilic cannabinoid produces antinociception that is lost in mice lacking TRPA1, providing an explanation for the analgesic activity of acetaminophen.
- David A Andersson
- , Clive Gentry
- & Peter M Zygmunt
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Genetic dissection of axon regeneration via in vivo electroporation of adult mouse sensory neurons
Dorsal root ganglion neurons can regenerate after injury, but the mechanisms underlying axon regrowth are unclear. To address this, an electroporation transfection method is developed that can alter the gene expression of dorsal root ganglion cells in a living adult mouse, providing a tool to study axon regeneration.
- Saijilafu
- , Eun-Mi Hur
- & Feng-Quan Zhou
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Tactile stimulation lowers stress in fish
The health benefits of massage therapy, like the reduction of stress, have so far only been shown in humans. This study uses modelling to demonstrate that, while visiting cleaner fish to have ectoparasites removed, the physical stimulation also acts to reduce stress in the coral reef fish,Ctenochaetus striatus.
- Marta C. Soares
- , Rui F. Oliveira
- & Redouan Bshary
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Article
| Open AccessExtrasynaptic vesicle recycling in mature hippocampal neurons
In the classical model, fast neuronal signalling occurs at specialized presynaptic terminals. Now, Ratnayakaet al. show that stimulus-driven fusion and recycling of synaptic vesicles can occur at axonal sites remote from conventional synapses. These findings have implications for dynamic forms of neuron–neuron communication.
- Arjuna Ratnayaka
- , Vincenzo Marra
- & Kevin Staras
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Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision
At light levels where both rods and cones are active, their signals converge into shared downstream retinal circuitry. Using HCN1 deficient mice, this study shows that the signals from cone photoreceptors are overwhelmed when rod output is not regulated, suggesting a mechanism for how these systems interact.
- Mathias W. Seeliger
- , Arne Brombas
- & Frank Müller
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miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells
The microRNA miR-137 is enriched in the brain of mice and induces the differentiation of adult neural stem cells. Now, Sun and colleagues report that miR-137 negatively regulates proliferation of neurons in embryonic mice and that TLX and LSD1 cooperate to negatively regulate miR-137 expression, blocking premature differentiation.
- GuoQiang Sun
- , Peng Ye
- & Yanhong Shi
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Review Article |
Integrating the biophysical and molecular mechanisms of auditory hair cell mechanotransduction
Hair cells of the inner ear transduce vibrations of the basilar membrane into electrical signals by a process known as mechanotransduction. Recent advances in genetic and molecular tools have led to an improved understanding of mechanotransduction as Peng and colleagues summarize in this Review.
- Anthony W. Peng
- , Felipe T. Salles
- & Anthony J. Ricci
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Synapse microarray identification of small molecules that enhance synaptogenesis
Large scale synapse assays can facilitate identification of drug leads. Shiet al. develop a 'synapse microarray' technology that enables sensitive, high-throughput, quantitative screening of synaptogenic events, and use it to identify novel histone deacetylase inhibitors that enhance synaptogenesis.
- Peng Shi
- , Mark A. Scott
- & Mehmet Fatih Yanik
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Behavioural memory reconsolidation of food and fear memories
Memory retrieval followed by extinction training has been shown to erase fear memories. Flavellet al. show that this approach also erases appetitive memories in rats and results from a modification of memory reconsolidation, which could be useful for the treatment of drug addiction.
- Charlotte R. Flavell
- , David J. Barber
- & Jonathan L.C. Lee
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NMDA receptor activation requires remodelling of intersubunit contacts within ligand-binding heterodimers
In non-NMDA glutamate receptors, intersubunit contacts within agonist binding domains affect functional desensitization. Now, NMDA receptor activation, but not desensitization, is shown to involve rearrangements at the heterodimer interface, suggesting that the intersubunit contacts of NMDA and non-NMDA receptors may have distinct functional roles.
- William F. Borschel
- , Swetha E. Murthy
- & Gabriela K. Popescu
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Electrosensory ampullary organs are derived from lateral line placodes in bony fishes
Ampullary organs are involved in electroreception, but whether these are derived from placodes, thickened ectoderm, is unclear. In this study, the ampullary organs of the primitive ray-finned fish,Polyodon spathula, are shown to develop from lateral line placodes, suggesting that this is the ancestral state in bony fishes.
- Melinda S. Modrell
- , William E. Bemis
- & Clare V.H. Baker
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Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells
The role of phosphatidylinositol(4,5)bisphosphate in exocytosis is unclear. This study shows that inhibition of the p110δ isoform of PI3-kinase promotes a transient increase in phosphatidylinositol(4,5)bisphosphate, leading to a potentiation of exocytosis in chromaffin cells.
- Peter J. Wen
- , Shona L. Osborne
- & Frédéric A. Meunier
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Article
| Open AccessInformation processing using a single dynamical node as complex system
The paradigm of reservoir computing shows that, like the human brain, complex networks can perform efficient information processing. Here, a simple delay dynamical system is demonstrated that can efficiently perform computations capable of replacing a complex network in reservoir computing.
- L. Appeltant
- , M.C. Soriano
- & I. Fischer
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Article
| Open AccessBacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration
Group BStreptococcuscauses meningitis in newborn infants but how the bacterium crosses the blood-brain barrier is unknown. Here, the bacterial pili adhesion molecule, PilA, is shown to bind to collagen and promote binding of the bacteria to integrins expressed on the blood-brain endothelium.
- Anirban Banerjee
- , Brandon J. Kim
- & Kelly S. Doran
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Article
| Open AccessMolecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels
The assembly mechanisms of heteromeric ion channels are poorly understood. Using a range of techniques, Shuartet al.determine the mechanism by which rod photoreceptor cyclic nucleotide-gated channels assume a 3:1 stoichiometry of CNGA1 and CNGB1 subunits.
- Noah G. Shuart
- , Yoni Haitin
- & William N. Zagotta
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Direct visualization of microtubules using a genetic tool to analyse radial progenitor-astrocyte continuum in brain
The development of radial progenitor cells and astroglia in the cerebral cortex depends on the microtubule cytoskeleton. Eomet al. have developed a new mouse model where the microtubules of astrocytes and radial glia cells are fluorescently tagged, facilitating the detailed study of microtubule dynamics and development in these cells.
- Tae-Yeon Eom
- , Amelia Stanco
- & E.S. Anton
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Article
| Open AccessActive sampling and decision making in Drosophila chemotaxis
Drosophila melanogaster larvae demonstrate chemotaxis towards odours but their navigation mechanism is poorly understood. Using computer-vision tracking, Gomez-Marinet al.show that larvae ascend odour gradients using an active sampling strategy that is analogous to sniffing in vertebrates.
- Alex Gomez-Marin
- , Greg J. Stephens
- & Matthieu Louis
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Article
| Open AccessParkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus
Pluripotent stem cells can be generated from the somatic cells of humans and are a useful model to study disease. Here, pluripotent stem cells are made from a patient with familial Parkinson's disease, and the resulting neurons exhibit elevated levels of α-synuclein, recapitulating the molecular features of the patient's disease.
- Michael J. Devine
- , Mina Ryten
- & Tilo Kunath
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Article |
Critical roles for EphB and ephrin-B bidirectional signalling in retinocollicular mapping
How retinoganglion cell axons project correctly to the superior colliculus is poorly understood. Here, projections are shown to require EphB1, EphB2 and ephrin-B1 to terminate in the medial superior colliculus, while ephrin-B2 is essential for the mapping of both dorsal and ventral axons.
- Sonal Thakar
- , George Chenaux
- & Mark Henkemeyer
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Relative comparisons of call parameters enable auditory grouping in frogs
Male túngara frogs produce overlapping mating calls, which poses a challenge for the female frog to group and assign multiple auditory signals to the correct source. Farris and Ryan shows that, like humans, the female frogs compare and group signals using the smallest relative difference in call parameters.
- Hamilton E. Farris
- & Michael J. Ryan
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Outlines of the pore in open and closed conformations describe the gating mechanism of ASIC1
The pore gating mechanism of the proton-activated sodium channel ASIC1 is poorly understood. Canessaet al.study the shape of the ion pathway in the ASIC1 channel in its open and closed states, and reveal the opening, closing and desensitization mechanisms of the channel.
- Tianbo Li
- , Youshan Yang
- & Cecilia M. Canessa
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Article
| Open AccessTonic excitation or inhibition is set by GABAA conductance in hippocampal interneurons
Ambient levels of the neurotransmitter GABA tonically activate GABAA. Song et al.show that GABA can have both excitatory and inhibitory effects on hippocampal interneurons and find that low levels of GABA-mediated conductance are excitatory, whereas higher levels result in shunting inhibition.
- Inseon Song
- , Leonid Savtchenko
- & Alexey Semyanov
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TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin
Nitric oxide can be produced by nitric oxide synthase or by nitrite reduction, but whether the latter occurs inside cells is unknown. Here, the TRPV3 ion channel is shown to induce nitrite-dependent nitric oxide production in keratinocytes, where it has a role in thermosensory behaviour and wound healing.
- Takashi Miyamoto
- , Matt J. Petrus
- & Ardem Patapoutian
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Article
| Open AccessHuman cryptochrome exhibits light-dependent magnetosensitivity
In animals, cryptochrome proteins are thought to be the detectors of the Earth's magnetic field, but humans have not been shown to posess mangetosensing capabilities. Foleyet al. demonstrate that the human cryptochrome protein, CRY2, when expressed in Drosophila melanogastercan mediate magnetoreception in a light-dependent manner.
- Lauren E. Foley
- , Robert J. Gegear
- & Steven M. Reppert
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Article
| Open AccessRequirement of calcium-activated chloride channels in the activation of mouse vomeronasal neurons
The vomeronasal organ detects pheromones, which are thought to activate TRPC2 channels on the surface of vomeronasal neurons. Using TRPC2 knockout mice, the authors show that urinary pheromones can also activate these neurons via calcium-activated chloride channels, suggesting a TRPC2-independent pathway for sensing pheromones.
- SangSeong Kim
- , Limei Ma
- & C. Ron Yu
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Ultrasonic frogs show extraordinary sex differences in auditory frequency sensitivity
Acoustic communication is important for the reproductive behaviour of frogs. Using acoustic playback experiments, Shenet al. show that calls from male concave-eared frogs (Odorrana tormota) evoke vocal responses and phonotaxis from females, but the females show no ultrasonic sensitivity.
- Jun-Xian Shen
- , Zhi-Min Xu
- & Shang-Chun Fan
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Vocalization frequency and duration are coded in separate hindbrain nuclei
Vocal communication is relatively common among fish: the midshipman being an example with a particularly wide dynamic range. In this paper, the authors demonstrate that different populations of hindbrain neurons are responsible for the frequency and duration of these calls.
- Boris P. Chagnaud
- , Robert Baker
- & Andrew H. Bass
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Article
| Open AccessNeural coding in a single sensory neuron controlling opposite seeking behaviours in Caenorhabditis elegans
The neuronal mechanisms responsible for thermal seeking behaviour inCaenorhabditis. elegansare not fully understood. In this study, the sensory neuron AFD is shown to be involved in the responses to both cold and warm temperatures by transmitting inhibitory and excitatory signals to the interneuron AIY.
- Atsushi Kuhara
- , Noriyuki Ohnishi
- & Ikue Mori
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Atomistic mechanism for the activation and desensitization of an AMPA-subtype glutamate receptor
Upon agonist binding, ionotropic glutamate receptors are activated and then become desensitized, but the detailed molecular events of this process are unclear. Here, molecular dynamics simulations are used to probe how conformational changes of the ligand-binding domain are transmitted to the transmembrane domain.
- Hao Dong
- & Huan-Xiang Zhou
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Developmental correspondence between action prediction and motor ability in early infancy
It is believed that infants map observed actions onto their own representation of the action, a hypothesis known as direct matching. By observing the gaze of infants and their grasping response, experimental evidence is provided to support the direct matching theory.
- Yasuhiro Kanakogi
- & Shoji Itakura
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Article
| Open AccessInteraction between prion protein and toxic amyloid β assemblies can be therapeutically targeted at multiple sites
The ability of synthetic amyloid β-protein to bind to prion proteins and alter synaptic plasticity has been previously reported. Here the relevance of this binding is investigated in brains of Alzheimer's disease patients and the interaction is shown to be blocked by antibodies to two distinct regions of prion proteins.
- Darragh B. Freir
- , Andrew J. Nicoll
- & John Collinge
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Article
| Open AccessCircadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus
Circadian rhythm is controlled by the suprachiasmatic nucleus and the mechanisms that control the rhythm are largely undiscovered. In this study, a G protein regulator, RGS16, is shown to be involved in the production of cyclic AMP that is required for the suprachiasmatic nucleus to maintain rhythm
- Masao Doi
- , Atsushi Ishida
- & Hitoshi Okamura
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The neural circuits and sensory channels mediating harsh touch sensation in Caenorhabditis elegans
The mechanisms by which animals distinguish between harsh and gentle touch are unclear. UsingCaenorhabditis elegansas a model system, the authors identify neural circuits and touch-sensitive ion channels that are required for harsh touch sensation.
- Wei Li
- , Lijun Kang
- & X.Z. Shawn Xu
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Recovery from chronic monocular deprivation following reactivation of thalamocortical plasticity by dark exposure
Amblyopia induced by chronic monocular deprivation can be reversed by dark exposure, followed by reverse deprivation in adulthood. The authors show that dark exposure in adulthood reactivates plasticity in the visual cortex, including thalamocortical synapses, promoting recovery from deprivation amblyopia.
- Karen L. Montey
- & Elizabeth M. Quinlan
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Food restriction enhances visual cortex plasticity in adulthood
Calorie restriction has been associated with increased life span and delayed decline of memory in animals, suggesting a role in neuronal plasticity. In this study, food restriction is demonstrated to enhance plasticity in the central nervous system and trigger the recovery from ocular deprivation in adulthood.
- Maria Spolidoro
- , Laura Baroncelli
- & Lamberto Maffei
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Engineering biosynthetic excitable tissues from unexcitable cells for electrophysiological and cell therapy studies
Patch-clamp recordings are used to study the function of ion channels, but the method does not allow the assessment of tissue-level function. Kirkton and Bursac introduce a biosynthetic system for the study of channel activity and electrical conduction, facilitating studies of ion channel function.
- Robert D. Kirkton
- & Nenad Bursac
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Optogenetic analysis of synaptic transmission in the central nervous system of the nematode Caenorhabditis elegans
Pair-wise electrophysiology is difficult inCaenorhabditis elegansbecause the recordings are relatively short-lived. In this study, the authors investigate the synaptic currents associated with escape responses by immobilizing worms on a micropatterned agar substrate and stimulating neurons using channelrhodopsin-2.
- Theodore H. Lindsay
- , Tod R. Thiele
- & Shawn R. Lockery
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Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors
N-methyl-D-aspartate receptors mediate excitatory synaptic transmission, and those containing GluN2D subunits have an unusually long deactivation time. Vance et al. show that the conformational variability of the ligand-binding domain and the structure of the activating ligand influence deactivation time.
- Katie M. Vance
- , Noriko Simorowski
- & Hiro Furukawa
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Frequency-dependent recruitment of V2a interneurons during fictive locomotion in the mouse spinal cord
The spinal V2a interneurons control left–right limb alternation during mouse locomotion, but only at high frequencies. In this study, the authors show that only half of these neurons are active during locomotion, and that they receive increasing synaptic drive to increase their activity as locomotion accelerates.
- Guisheng Zhong
- , Kamal Sharma
- & Ronald M. Harris-Warrick
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Article
| Open AccessNeural crest cells organize the eye via TGF-β and canonical Wnt signalling
In the developing eye, the lens and retina are derived from different embryonic tissues, and how these two structures develop next to each other is of interest. In this study, the authors show that transforming growth factor-β secreted by neural crest cells is critical for the positioning of the lens next to the retina.
- Timothy Grocott
- , Samuel Johnson
- & Andrea Streit
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Article |
Subcellular in vivo time-lapse imaging and optical manipulation of Caenorhabditis elegans in standard multiwell plates
The nematodeCaenorhabditis elegans is a widely used model organism for visualizing development, ageing and other phenomena, but high-throughput imaging requires immobilization of the animal. Rohde and Yanik report a rapid immobilization and imaging method for the high-throughput screening of C. elegans.
- Christopher B. Rohde
- & Mehmet Fatih Yanik
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Article
| Open AccessRepresentational format determines numerical competence in monkeys
Many animals can do simple quantity discrimination, but they often perform poorly when food is used. Here, the authors show that monkeys are good at food quantity discrimination when they are not allowed to eat it, suggesting that the mental representation of the stimuli is more important than the physical quality.
- Vanessa Schmitt
- & Julia Fischer
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Article
| Open AccessErrors in the measurement of voltage-activated ion channels in cell-attached patch-clamp recordings
Voltage-activated ion channels can be measured in neurons using the cell-attached patch-clamp technique. Williams and Wozny show that this technique is prone to errors that are caused by the flow of current through the ion channels; a method to correct for these discrepancies is described.
- Stephen R. Williams
- & Christian Wozny
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Article |
A modern ionotropic glutamate receptor with a K+ selectivity signature sequence
Glutamate is the major excitatory neurotransmitter in the mammalian nervous system. Here, a glutamate receptor is reported that has properties intermediate to those of bacterial and eukaryotic glutamate-gated ion channels, suggesting a link in the evolution of ionotropic glutamate receptors.
- H. Janovjak
- , G. Sandoz
- & E. Y. Isacoff
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Article |
Measurement of cochlear power gain in the sensitive gerbil ear
The cochlear amplifier in the inner ear is thought to mediate sensitivity to soft sounds, but this power gain has not been measured directly. Renet aluse an interferometer to measure the volume displacement and velocity of the cochlear partition and demonstrate experimentally that the cochlea amplifies soft sounds.
- Tianying Ren
- , Wenxuan He
- & Peter G. Gillespie
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Article
| Open AccessRetinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state
There is much interest in generating motor neurons from embryonic stem cells because they may be useful for the study of neurodegenerative disease. Pataniet al. show that in the absence of retinoic acid, neurons with features of medial motor columnar neurons can be generated from human embryonic stem cells.
- R. Patani
- , A. J. Hollins
- & S. Chandran
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Article
| Open AccessIh-mediated depolarization enhances the temporal precision of neuronal integration
In neurons, GABAA receptors mediate feed-forward inhibition by shunting excitatory currents and hyperpolarizing neurons. Here, the authors show that the hyperpolarization-activated mixed cation current is critical for determining the resting membrane potential and reversal potential for GABAA-mediated currents.
- Ivan Pavlov
- , Annalisa Scimemi
- & Matthew C. Walker
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Article
| Open AccessGipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human
Progressive sensorineural hearing loss affects many people, but the underlying genetics remain largely undefined. Here, the authors identify mutations inGIPC3in mice and two consanguineous families that lead to hearing loss and in mice cause defects in the structure of stereocilia bundles and audiogenic seizures.
- Nikoletta Charizopoulou
- , Andrea Lelli
- & Konrad Noben-Trauth
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Article
| Open AccessGlia- and neuron-specific functions of TrkB signalling during retinal degeneration and regeneration
The central nervous system contains glial cells, which have been shown to have an important role in neuronal survival. Haradaet al. use transgenic mouse models to show that TrkB, a receptor for the growth factor brain-derived neurotrophic factor, is required for retinal Müller glial cells to provide neuroprotection and regeneration.
- Chikako Harada
- , Xiaoli Guo
- & Takayuki Harada
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