Nöroloji/Nöroşirurji

Hemberger et al. examine the actions of single neurons on surrounding networks in reptilian cortex. Cortical pyramidal neurons can initiate neuronal sequences reminiscent of hypothesized “synfire chains,” suggesting the existence of a landscape of preferred paths for cortical information flow.

Tian, Gachechiladze, and Ludwig et al. present a CRISPR interference-based platform for genetic screens in human iPSC-derived neurons. This platform enables systematic elucidation of gene function in human neurons and reveals neuron-specific roles of genes for survival, transcriptomics states, and morphology.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, inflammatory disorder of the central nervous system that has a prevalence of 0.5 to 10 persons (predominantly women) per 100,000 population. It is characterized mainly by recurrent optic neuritis and myelitis, and

An electrophysiological and biopsy study of 106 patients with chronic inflammatory demyelinating polyradiculoneuropathy identifies differences between disease subtypes Chronic inflammatory neuropathies include multifocal motor neuropathy, which is purely motor and often associated with complement-fixing antibodies to ganglioside GM1, paraproteinaemic demyelinating

Conventional antidepressants have limited efficacy and many side effects, highlighting the need for fast-acting and specific medications. Holz et al. utilize cell-membrane-permeable TAT-fused peptides, which specifically modulate glutamatergic neurotransmission, as a novel strategy for rapid and effective antidepressant treatment.

Kwart and Gregg et al. generated a comprehensive panel of isogenic autosomal dominant familial Alzheimer’s disease (fAD) mutant human iPSCs. Differentiated neurons demonstrated common alterations in early endosomes mediated by accumulation of β-CTF, not Aβ.

Mayrhofer et al. map the location of mouse tongue-jaw motor cortex, finding that its neuronal activity encodes licking direction and is necessary for contralateral goal-directed licking but does not encode which sensory cue initiates licking, in contrast to sensory cortex.

You can’t walk into a pediatric intensive care unit (PICU) anywhere in the world without being viscerally struck by sights, smells, and sounds that can easily overwhelm the uninitiated. Every child in a PICU is attached to various monitors that

Tedeschi et al. identify ADF/cofilin as a key driver of axon regeneration in adult dorsal root ganglion neurons. Specifically, enhanced actin turnover by the ADF/cofilin severing function controls axon regeneration in the adult CNS.

Neurological researchers are not typically known as ardent activists, and might be viewed to prefer quiet labs or busy clinical centres rather than the spotlight of the press and social media. But the stereotypes are being challenged. The Director of

Nigam et al. show that synergistic interactions represent an integral part of cortical computations in laminar circuits during wakefulness. Synergistic interactions allow columnar neural populations to efficiently encode sensory information even when receptive fields overlap and shared noise between cells is

To the Editor: Superoxide dismutase-1 (SOD1) is a ubiquitously expressed antioxidant enzyme. Mutations in SOD1 are associated with dominantly inherited amyotrophic lateral sclerosis, probably caused by the toxic effects of the protein rather than by loss of enzymatic activity. Here

Cell-specific gene modification is immensely crucial for basic biology as well as to deliver precise gene therapy. Garcia-Marques et al. present a breakthrough technology to genetically access specific cell types based on the expression of a precise combination of genes.

Journal of Neurotrauma, Volume 36, Issue 16, Page 2377-2384, August 15, 2019.

Journal of Neurotrauma, Volume 36, Issue 15, Page 2279-2286, August 1, 2019.

Gene therapy has provided treatment options for diseases that are beyond the reach of traditional approaches. Since 2016, between the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), six gene therapy products have been approved: two

Andrusiak et al. identify liquid-like granules of TIAR-2 as inhibitory for axon regeneration. Serine and tyrosine residues within the prion-like domain are essential for granule formation and function. This study provides a functional in vivo readout for a phase-separated compartment.

To the Editor: Superoxide dismutase-1 (SOD1) is a ubiquitously expressed antioxidant enzyme. Mutations in SOD1 are associated with dominantly inherited amyotrophic lateral sclerosis, probably caused by the toxic effects of the protein rather than by loss of enzymatic activity. Here

Haesemeyer et al. train convolutional neural networks to navigate temperature gradients to reveal shared representations and processing in artificial and biological networks. Constrained by zebrafish behavior, artificial networks critically rely on fish-like units and make testable predictions about the brain.

Hasselmann, Coburn, et al. validate a new xenotransplantation paradigm to study iPSC-derived human microglia in vivo. This chimeric approach rectifies many of the deficits observed in culture models, providing new insight into the functional and transcriptional responses of human microglia to inflammatory

Ren et al. identify presynaptic neurons innervating individual excitatory neuron clones that constitute microcircuits in the sensory cortex and reveal that input neurons in the frontal cortex are organized in discrete vertical clusters and preferentially form synapses with each other.

Bonnefont et al. show that Bcl6 promotes neurogenesis by directly repressing genes belonging to the major signaling pathways promoting cortical progenitor self-renewal. These data indicate that a single cell-intrinsic factor represses multiple extrinsic signaling pathways to ensure irreversible neurogenic commitment.

Sensory stimuli and behavioral reinforcement can be separated by long silent intervals. Guo et al. characterize a distributed neural circuit in the mouse forebrain that supports auditory fear learning by linking brief sounds with aversive events that occur many seconds later.

The world’s climate crisis has spared no one. Science tells us that the harms of climate change will worsen with time if we fail to take substantial actions now to reduce carbon pollution. In the United States, the growing burden

A steady protein supply is critical to synaptic function. Here, Fonkeu et al. present a theoretical framework, validated by experimental data, that details how local and dendritic mRNAs shape dendritic protein dynamics across short and long timescales.

Hierarchical movement sequences are often assumed to mirror an anatomical hierarchy of brain regions. Using representational fMRI analysis, Yokoi and Diedrichsen challenge this common assumption. Although the primary motor cortex represents elementary movements, chunk and sequence representations coexist in the

Gamma oscillations are hypothesized to temporally coordinate sensory encoding. Shin and Moore found a distinct subtype of fast spiking interneurons (FS) in SI that are nonsensory responsive and spike regularly at gamma intervals. These “gamma regular nonsensory FS” could potentially

Presentation of Case. Dr. Doll L. Golden (Medicine): A 65-year-old woman was admitted to this hospital because of falls, weakness, dark urine, and difficulty swallowing. Approximately 35 years before the current admission, the patient underwent staged male-to-female sex reassignment surgery

To the Editor: Superoxide dismutase-1 (SOD1) is a ubiquitously expressed antioxidant enzyme. Mutations in SOD1 are associated with dominantly inherited amyotrophic lateral sclerosis, probably caused by the toxic effects of the protein rather than by loss of enzymatic activity. Here

Pan et al. identify a microcircuit in the dorsal spinal cord that transmit mechanically evoked itch. Sensitization of this pathway is required for chronic itch development.

Sohn et al. found that prior beliefs warp neural representations in the frontal cortex. This warping provides a substrate for the optimal integration of prior beliefs with sensory evidence during sensorimotor behavior.

An extensive single-cell catalog of cell types in the mid-gestation human neocortex extends our understanding of early cortical development, including subplate neuron transcriptomes, cell-type-specific regulatory networks, brain evolution, and the cellular basis of neuropsychiatric disease.

Presentation of Case. Dr. Priya Srikanth (Neurology): A 31-year-old woman was evaluated in the emergency department of this hospital because of vision loss. Three weeks before presentation, blurry vision in the left eye developed gradually, with perception of distant objects

Neurologists are keen to remind their trainees that ‘it’s all in the history’. An illness’s time course is a particularly important part of the history, providing the time signature for the underlying pathological process and thus significantly narrowing the differential

Have we found the ‘dynamic lesion’ of Jean-Martin Charcot in functional neurological disorders? At the end of the 19th century, hysterical symptoms were regarded by one of the founders of modern neurology, Jean-Martin Charcot, as manifestations of a ‘dynamic lesion’

Microglial receptors CD33 and TREM2 exhibit opposite effects on Aβ pathology and microglial activity in AD mice. In crosstalk between these receptors, TREM2 is required for differential gene expression in 5xFAD mice deficient for CD33 and acts downstream of CD33.

The most common inherited cause of intellectual and developmental disability worldwide is fragile X syndrome, caused by a mutation in the FMR1 gene on the X chromosome. To accelerate the development of effective interventions to prevent or treat fragile X

Xu et al. show that in the Drosophila visual system, DIP IgSF proteins are not necessary for synaptogenesis but regulate synaptic specificity by promoting synapses to form between specific cell types.

Xin et al. studied the computational mechanism for transforming sensory information into meaningful categories in the auditory cortex using two-photon imaging. Cortical neurons are dynamically recruited to enhance discrimination for stimuli near decision boundaries. Categorical decisions can be accurately decoded from

Journal of Neurotrauma, Volume 36, Issue 14, Page 2153-2166, July 15, 2019.

Flexible behavior requires a memory of previous interactions with the environment. The medial prefrontal cortex persistently represents value-based decision variables, bridging the time between choices. These decision variables are sent to the dorsomedial striatum to bias action selection.

Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information by sharing relevant background and reasoning with the reader (regular type). The authors’ commentary follows.

How does the brain process natural versus drug rewards? Alhadeff et al. demonstrate that food and drugs signal from the periphery to the hypothalamus via distinct pathways. Furthermore, bidirectional and coordinated interactions between hypothalamic and dopamine circuits potentiate responses to rewards.

Using high-content screening, we identified a class of planar small molecules that can (1) modulate the dynamics of neurodegeneration-linked stress granules (SGs), (2) reduce SG association of ALS-linked RNA-binding proteins, and (3) prevent accumulation of TDP-43 within persistent cytoplasmic puncta.

Journal of Neurotrauma, Volume 36, Issue 13, Page 2053-2064, July 1, 2019.

Non-canonical Wnt signaling through the Ryk receptor establishes regional subdomains within the MGE along the rostral-caudal axis. These subdomains are defined by graded Ryk signaling, which regulates the proportions of parvalbumin and somatostatin cortical interneurons produced during development.

Sedation is a component of the care of critically ill patients who are undergoing mechanical ventilation, but the appropriate choice of a primary sedative agent remains uncertain. Propofol and midazolam, which act mainly through pathways mediated by γ-aminobutyric acid, are

Here, Bray et al. used a variety of transgenic mice to demonstrate high survival and regenerative ability of one neuronal type in the retina and show several factors within these neurons, including thrombospondin-1 and syndecan-1 that confer high regenerative capacity.

The orbitofrontal cortex (OFC) plays a critical role in guiding decisions in dynamic environments. Groman et al. use a directionally specific viral ablation approach to demonstrate that OFC circuits encode separable reinforcement-learning processes that guide decisions.

Zheng et al. defined distinct intrinsic physiological properties and transcriptome profiles of eight somatosensory neuron subtypes and further revealed subtype-specific contributions of differentially expressed potassium channels to the intrinsic membrane properties in these sensory neurons.

Haploinsufficiency in the gene SCN2A, which encodes the sodium channel NaV1.2, has strong autism association. Spratt et al. show that Scn2a contributes to dendritic excitability in mature neocortical pyramidal cells, where its loss impairs excitatory synaptic function and plasticity.

Rhoades et al. find the smooth monostratified retinal ganglion cells in the primate retina have unusual receptive fields consisting of multiple hotspots. This differs from classic center-surround receptive field models and suggests a role in nonlinear visual computation.

Reward outcomes depend on the stimulation protocol used to activate nucleus accumbens medium spiny neuron (MSN) subtypes. In this issue of Neuron, Francis et al. demonstrate rebalanced MSN subtype excitation driven by high-frequency stimulation and substance P release.

Sengupta and Holmes use in vivo imaging, optogenetic, electrophysiological, and histological approaches to investigate the circuit-specific role of the DRN→BA 5-HT pathway in fear learning. They show this pathway is uniquely positioned, functionally and anatomically, to shape fear memory.

Kalincik T, Kubala Havrdova E, Horakova D, et al. Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis. J Neurol Neurosurg Psychiatry 2019;90:458–68. Under heading Fingolimod vs teriflunomide: “(HR 0.77, 95% CI 0.63 to 0.95, p=0.03; figure 3C)” should

Zhou et al. identified a neural circuit related to VTAGABA+ neurons that mediates visually evoked innate defensive responses, involving the SCGlut+- VTAGABA+-CeA pathway.

Cervical myelopathy, also known as cervical spondylotic myelopathy, is a common spinal cord disorder. The disease can reduce quality of life similarly to diabetes or cancer, but data on its prevalence and incidence are scarce. Myelopathy is a progressive condition

Chabrol et al. show that the cerebellum is directly involved in maintaining preparatory activity in the premotor neocortex during learned, goal-directed behavior. Their results suggest the cerebellum provides a learned timing signal required for motor preparation in the neocortex.

The paraventricular nucleus of the thalamus is a substrate underlying reward seeking. Otis, Zhu, et al. demonstrate that projection-defined thalamic neurons are controlled by dissociable response features in cortical and hypothalamic inputs during reward processing.

Using a three-step approach for systematic screening, Ma et al. identified GABAergic neurons in CeA and glutamatergic neurons in the posterior thalamus that promote NREM sleep. Each population uses both the NTS peptide and a classical neurotransmitter to promote sleep.

Journal of Neurotrauma, Volume 36, Issue 12, Page 1909-1922, June 15, 2019.

Collado-Torres et al. describe the BrainSeq Phase II gene expression resource encompassing two brain regions from 551 genotyped individuals spanning the entire human lifespan (286 with schizophrenia). This resource can answer region-specific questions about development and schizophrenia and its genetic risk.

Journal of Neurotrauma, Volume 36, Issue 11, Page 1683-1706, June 2019.

Trautmann et al. ask whether spike sorting is necessary for investigation at the level of neural populations. They show that combining multiple neurons on each electrode introduces only minor distortions in estimates of neural population state.

The mammalian thirst circuit receives temporally distinct satiation signals by both liquid gulping action and gut osmolality sensing. These thirst satiation signals are functionally separable from the reward-related circuit activity.

Audette et al. use automated training and in vitro electrophysiology to define cortical circuit changes during sensory-association learning. Pathway-specific analysis identifies higher-order thalamic inputs to sensory cortex as a site of synaptic potentiation during the earliest stages of learning.

Kunst et al. generated a digital atlas of the larval zebrafish brain containing over 2,000 neuron morphologies, most of them previously unknown. These data are used to generate the first brain-wide wiring diagram with single-cell resolution for a vertebrate species.

The single-trial dynamics of LIP neurons during decision-making are under debate. Zoltowski et al. extend latent stepping and ramping models of LIP dynamics and find that a robust fraction of LIP neurons is better described by each model class.

We use single-cell RNA-seq analysis to comprehensively profile gene expression during mouse retinal development. We find major differences between early and late-stage, as well as primary and neurogenic, progenitors. We also find that NFI factors control cell-cycle exit and generation

It is often said that neurology is a diagnostic specialty. Colleagues in other specialties sometimes characterise neurologists as being interested in diagnosis but not in treatment. A superficial glance at the contents of this issue might add weight to that

Zhang et al. (2019) find that amacrine cell hyperactivation after RGC axotomy prevents IGF1 responsiveness. Blocking amacrine cell synaptic activity potentiates IGF1-mediated axon regeneration by maintaining IGF1R localization to primary cilia, a localization that is normally lost in injured RGCs.

Stroke is a leading cause of mortality and morbidity globally. Its highest incidence has been reported in Asia, especially China, followed by eastern Europe. The projections from the Burden of Stroke in Europe Report now indicate that the total number

Presynaptic CaV2.1 channels are confined in nanodomains, for which size and dwell time are modulated by network activity. Heck et al. show that changing the affinity to scaffold proteins by alternative splicing of CaV2.1 directly affects short-term plasticity.

The evidence on the association between allergies and multiple sclerosis (MS) disease activity is scarce. In this issue of JNNP, Fakih and colleagues report that patients with MS and food allergies have a higher disease activity compared with patients with

Pagani et al. investigated the temporal and spatial signature of GRP signaling, a key element of spinal itch relay. They find that GRP signals build up slowly and rather diffusely during stimulation, possibly explaining why itch is difficult to localize.

Smith and Lin et al. identify a glutathione S-transferase that decreases mitochondrial fusion in axons of neurons through unbiased genetic screening using Drosophila. gfzf mutants induce sustained hyperfusion through an enhanced oxidation of glutathione that increases the function of mitofusin.

The functional role of dorsomedial striatum low-threshold spiking interneurons (LTSIs) in behavior has been largely unexplored. Holly et al. show that LTSIs have reward outcome-associated activity that decreases with and causally modulates goal-directed learning.

Journal of Neurotrauma, Volume 36, Issue 10, May 15, 2019.

Saneyoshi et al. find that stimulation of single spine causes rapid formation of a reciprocally activating signaling complex between CaMKII and a Rac-GEF Tiam1, which stably activates Rac1 and maintains enlarged spine structure during LTP.

Chronic application of patterned visual stimulation in neurodegeneration mouse models to entrain gamma oscillations results in preservation of neuronal and synaptic density across multiple brain regions.

Female fruit flies are less receptive after mating because of ejaculate from previous mating partners and the act of copulation itself. Shao et al. characterize a neural circuit mediating the sensory signals of copulation that lead to reduced female receptivity.

Sabariego et al. provide evidence that mEC is required for working memory but not by sustaining hippocampal time cell activity during delay periods. Rather, loss of mEC inputs decreased the differential hippocampal coding between spatial locations during the encoding phase of

Journal of Neurotrauma, Volume 36, Issue 9, Page 1389-1398, May 1, 2019.

Ferent et al. elucidate how the Shh receptor Boc works together with Ptch1 to transduce the Shh signal in axon guidance. They demonstrate that Numb-mediated internalization of Boc is required for Ptch1 internalization, activation of signaling, and Shh-mediated axon guidance.

How VIP interneurons modulate network-level activity to regulate behavior is not understood. Lee et al. show that in the elevated plus maze, prefrontal VIP neurons promote open arm avoidance by disinhibiting theta-frequency communication that transmits anxiety-related information across hippocampal-prefrontal networks.

Firing rate set-point regulation has puzzled researchers for decades. Our findings show that mitochondrial DHODH meets the criteria of a bone fide regulator of activity set points and suggest lowering firing set point as a new strategy to treat epilepsy.

Meda et al. show that in chronic pain states, mediodorsal thalamic (MD) inputs to the anterior cingulate cortex (ACC) undergo pathway-specific changes. As a result, MD-ACC inputs suppress the activity of many subcortically projecting ACC neurons, thereby driving negative pain-related affect.

Eating calorically dense, palatable foods is a major contributor to obesity and binge eating. In this article, Hardaway et al. identify a central amygdala brain circuit expressing the neuropeptide prepronociceptin in mice that promotes palatable food consumption and reward.

Neocortical circuits are comprised of intermingled excitatory projection neuron and inhibitory interneuron subtypes. Wester et al. show that fate-switching corticocortical projection neurons to a subcerebral type selectively influences the lamination, circuit integration, and gene transcription of CGE-derived interneurons.

Grid cells in entorhinal cortex underlie spatial orientation and path finding. Bao et al. show that entorhinal grid-like codes with behavioral relevance emerge when humans mentally navigate an olfactory landscape, highlighting potential neural mechanisms for locating odor sources in odiferous environments.

Jiang-Xie et al. identified a specific group of hypothalamic neurons (AANs) commonly activated by multiple classes of general anesthetics. Stimulation of AANs potentiates slow-wave sleep and general anesthesia (GA), whereas inhibition of AANs disrupts natural sleep and destabilizes GA.

Alternative splicing of presynaptic neurexin-1 and -3 at splice site 4 is shown to regulate the receptor composition of excitatory synapses. Neurexin-1-SS4+ increases NMDA receptor responses, whereas neurexin-3-SS4+ suppresses AMPA receptor responses. Thus, presynaptic neurexin alternative splicing shapes the postsynaptic

In this work on glutamate corelease by dopamine neurons, Silm et al. show that an individual neuron expresses two classes of synaptic vesicle that form through distinct mechanisms and transmit distinct information due to differences in frequency dependence.

Su et al. demonstrate that VTA GABA neurons signal aversion to itch and DA neurons mediate scratching-associated reward. Differential activation and function of VTA neurons may underlie the progression of vicious itch-scratch cycles.

Whether and how astrocytes release glutamate to regulate neuronal function are debated. Yang et al. show that Swell1 volume-regulated anion channel is a glutamate-releasing channel in astrocytes, which regulates basal synaptic transmission and contributes to excitotoxicity in ischemic stroke.

Preliminary results from a feasibility study suggest a potential role for flavonoid enriched cocoa to treat fatigue, one of the most challenging symptoms of multiple sclerosis In their JNNP paper, Coe et al report the preliminary results of a feasibility

Liang et al. describe neural outputs from the Drosophila circadian pacemaker network regulating locomotor rhythms: via a specific dopamine relay, the network forms parallel connections to the central complex, the pre-motor area dictating the balance between rest and activity.

On Feb 11, 2019, the US Food and Drug Administration (FDA) took action against 17 companies that sell dietary supplements, for claiming that they can treat Alzheimer’s disease. Scott Gottlieb, the FDA Commissioner at the time, released a statement explaining

Zheng et al. demonstrate that successful pattern separation of emotional stimuli is associated with bidirectional amygdala-hippocampal interactions via theta band (3–7 Hz). In contrast, unidirectional influence from the amygdala to the hippocampus via alpha band (7–13 Hz) leads to overgeneralization errors (i.e., failure

Kister I, Spelman T, Alroughani R, et al. Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study. J Neurol Neurosurg Psychiatry 2016;87:1133-7. doi: 10.1136/jnnp-2016-313760 In this article there was a discrepancy between the text and

Journal of Neurotrauma, Volume 36, Issue 8, Page 1195-1202, April 15, 2019.

Journal of Neurotrauma, Volume 36, Issue 7, Page 975-987, April 1, 2019.

Suver et al. describe how walking flies use their two antennae to measure wind direction. They describe a mechanosensory pathway that encodes antennal movements, with higher-order neurons combining information from the two antennae to linearly encode wind direction.

Azevedo et al. identify a subpopulation of neurons expressing the dopamine receptor 2 (D2R) within the hippocampus that is activated by food. They show that these neurons regulate food intake and the encoding of a food-place memory.

Figure 1.

Gaffield et al. find that sensory stimuli enhance climbing fiber responsiveness, leading to larger Purkinje cell Ca2+ events. This integrative process is unaffected by local neural circuits, indicating the primacy of the inferior olive in instructional signaling.

Goldstein et al. describe the location of the sodium spike initiation zone (Nav-SIZ) in nociceptive peripheral terminals in vivo and show that this location is dynamic. During inflammation, the location of Nav-SIZ shifts toward the terminal end, hence increasing nociceptive excitability

To the Editor: Chronic subdural hematoma recurs in 3 to 39% of patients after evacuation by means of neurosurgery. Postoperative computed tomography (CT) often shows residual hematoma that may or may not resolve over time, and the benefit of routine

Feng et al. develop and validate a pair of genetically encoded GPCR-activation-based norepinephrine sensors, which, for the first time, enable specific in vivo measurement of norepinephrine dynamics during stressful behaviors with high spatiotemporal resolution in zebrafish and mice.

The PF of the intralaminar thalamus is implicated in human neuropsychiatric disease. Mandelbaum et al. deconstruct the mouse PF using transcription, electrophysiological, and whole-brain anatomical analyses. They reveal organization of the PF that bridges molecular, cellular, and circuit levels, forming cortical-PF-cortical

Axon growth requires an enormous signaling matrix as the underlying code for building the nervous system. In a genetic screen, Bonanomi et al. identify p190RhoGAP as a critical regulatory switch that silences contextually inappropriate guidance signals for precise wiring of neuronal

Prefrontal cortex plays an essential role in fear expression. Xu et al. reveal a disinhibitory microcircuit in prefrontal cortex through interactions between interneuron subtypes and suggest that SST INs-mediated disinhibition represents an important circuit mechanism in gating social fear behavior.

Li et al. discover that PVHPDYN neurons, additively with PVHMC4R neurons, are responsible for PVH-mediated satiety. Both PVH neurons are distinct, are equipotent, and use parallel projections to different aspects of the parabrachial complex to cause satiety and prevent obesity.

Most patients referred to the neurology service are seen only once or twice. For these patients a diagnosis can be made at the first consultation and treatment and advice provided. This can be characterised as a ‘type A’ strategy, when

Massaly et al. identify a pain-induced enhancement in the kappa opioid system within nucleus accumbens, which drives pain-associated negative emotional states. These results provide a functional substrate for therapies that would circumvent pain-induced affective disorders.

Despite the importance of incorporating sex as a variable in experimental and clinical studies being recognised by the US National Institute of Mental Health already in 2011, and subsequently by other funding agencies in the USA and Europe, substantial evidence

Liu et al. demonstrate that the nucleoporin Seh1 functions in oligodendrocyte differentiation, myelination, and post-injury remyelination by assembling a Seh1/Olig2/Brd7 transcription complex at nuclear periphery.

Testing patients with hippocampal damage, Vikbladh et al. demonstrate that model-based planning and place memory rely on a common hippocampal substrate. The study bridges the reinforcement learning and spatial memory literatures to clarify the scope of hippocampal contributions to behavior.

Figure 1.

TDP-43 aggregation is the major hallmark of multiple neurodegenerative diseases, including ALS and FTD. Gasset-Rosa et al. demonstrate that transient stress induces long-lasting cytoplasmic TDP-43 de-mixing independent of stress granules, driving nuclear import defects, nuclear TDP-43 clearance, and cell death.

Bennett et al. divide the mouse pulvinar (LP) into 3 subregions with distinct anatomical connections and functional properties. They find that the superior colliculus conveys object motion to ventral stream cortical areas via posterior LP, whereas anterior LP targets dorsal stream

Chandelier cells (ChCs) are the only interneuron subtype that selectively innervates the axon initial segment (AIS) of pyramidal neurons (PyNs) in the neocortex; yet, the underlying mechanisms are unknown. Tai et al. reveal that neocortical ChC/PyN AIS innervation requires ankyrin-G-clustered L1CAM.

Journal of Neurotrauma, Volume 36, Issue 6, Page 835-844, March 19, 2019.

Journal of Neurotrauma, Volume 36, Issue 6, Page 845-852, March 19, 2019.

VanRyzin et al. demonstrate that microglia in the developing amygdala engulf and kill otherwise viable newborn astrocytes, establishing sex differences in social circuits. This process, which depends on gonadal hormones and endocannabinoid signaling, promotes juvenile play by males.

Zimmerman et al. define distinct neurotransmitter and circuit mechanisms that gate the flow of tactile sensory information from the periphery into the spinal cord and characterize their roles in tactile sensitivity and behaviors.

Animals engage in local search behavior after recent encounters with food-related sensory cues. López-Cruz et al. show that parallel chemosensory or mechanosensory circuits can independently trigger local search after food removal in C. elegans, each using a similar glutamate receptor module.

Stella et al. examine the dynamical properties of reactivated spatial trajectories in the hippocampus following non-stereotypical exploration and find that reactivated trajectories are governed by a Brownian diffusion process that occur at varying lengths and timescales, without directly reflecting behavior.

Journal of Neurotrauma, Volume 36, Issue 5, Page 641-649, March 1, 2019.

Deng et al. propose the concept of the chemoconnectome (CCT) as the entirety of all neurotransmitters, neuromodulators, neuropeptides, and their receptors and the approach of chemoconnectomics to trace neural circuitry anatomically and functionally.

Gene mutations associated with painless phenotypes offer great insight for analgesic development. Using a multi-modal approach, McDermott et al. show that mutations in the voltage-gated sodium channel NaV1.7 cause congenital insensitivity to pain due to a lack of functional nociceptors.

Adler et al. reveal mechanisms underlying learning-dependent sequential activation of pyramidal neurons in the primary motor cortex. SST-expressing interneurons and CaMKII-dependent synaptic plasticity control the establishment of sequential activity during motor training and prevent the interference from new learning.

Zhang et al. uncover the mystery of sub-quanta and quanta during vesicular release of multi-neurotransmitters. Catecholamine sub-quanta are jointly produced by fusion pores and the vesicular matrix, whereas the co-released ATP quanta are fully released during transient fusion events.

Objectives To assess the safety and efficacy of SFX-01 after subarachnoid haemorrhage. Design SFX-01 is a synthetic agent that contains sulforaphane that has been shown to be neuroprotective in animal models of subarachnoid haemorrhage. This is a phase II double-bilinded,

Farías et al. report that the localization of the endoplasmic reticulum (ER) in the axon is controlled by the interaction between ER-shaping proteins and the microtubule cytoskeleton. Local ER and microtubule crosstalk promotes ER tubule-microtubule stabilization and drives neuronal polarity.

Mayer et al. develop a microfluidics-based approach that links calcium imaging and single-cell transcriptomics to study cellular responses to neurotransmitters in the developing human neocortex. They reveal dynamically changing response profiles as progenitor cells differentiate to diverse types of neurons.

The development and introduction of monoclonal antibodies for migraine prevention that target calcitonin gene-related peptide (CGRP) or the CGRP receptor is one of the most important advances in migraine therapy in decades. For many neurologists, it came as a surprise,

Learning to predict a threat is crucial for survival. Trusel et al. identify the plasticity of neural circuit elements within the lateral habenula as a mechanism instrumental in guiding anticipation and avoidance of external aversive events.

Kornysheva et al. use non-invasive magneto-encephalography in humans to decode the preparation of upcoming actions in a sequence. They reveal that the brain preactivates a template of sequence order and that this template predicts the accuracy of subsequent execution.

Parkinson’s disease is a common and debilitating age-related neurodegenerative disease that is increasing rapidly in prevalence and is expected to affect 14 million people worldwide by 2040. The disorder is defined pathologically by the accumulation of a misfolded protein, α-synuclein,

Tsai et al. describe how the biosynthesis of specific phospholipids is linked to neurodegeneration and synaptic vesicle loss in adult Drosophila photoreceptors. Neurodegeneration is dependent on activity, and vesicle depletion engages a transcriptional feedback loop that includes SREBP and tetraspanins.

Zhang et al. discover a PTBP2-orchestrated neural-specific alternative splicing program essential for robust axon formation. These findings could shed light on axon pathophysiology in diseases and how axonogenesis happens only in neurons but not in any other cells.

Journal of Neurotrauma, Volume 36, Issue 4, Page 517-522, February 15, 2019.

A 21-year-old man was found unresponsive in a park, with a 1-gallon container of green liquid, approximately half of it gone, nearby. The label was not legible, but the liquid was presumed to be antifreeze. The man was brought to

Mechanisms by which Zika virus leads to microcephaly are poorly understood. Here, Li et al. demonstrate the Zika protease, required for viral replication, associates with host proteins and cleaves Septin-2, a protein required for neural cell division.

Akin and Bajar et al. report that stimulus-independent neural activity occurs in cell-type-specific patterns during synapse formation in Drosophila. Their findings suggest that neural activity may be a fundamental feature of brain development.

Direction-selective retinal ganglion cells encode visual motion but also respond to luminance changes. Kühn and Gollisch report that this dual-feature sensitivity creates ambiguities for decoding complex motion stimuli. Population decoding resolves these ambiguities and provides a synergistic motion readout.

Few tools in neuroscience allow long-term synapse inhibition with light. We engineered botulinum neurotoxin B so that it can be switched on with blue light. Light activation results in robust proteolysis of VAMP2, a SNARE protein universally required for neurotransmitter

Green et al. show that activation of the mast cell receptor Mrgprb2/X2 by the neuropeptide substance P leads to cytokine release and recruitment of immune cells contributing to inflammatory pain.

Tan et al. reveal a key mechanism that underlies signaling from endothelial cells to neurons in the brain. They identify that the endothelium-secreted protein semaphorin 3G (Sema3G) regulates synaptic structure and plasticity in hippocampal neurons through its neuronal neuropilin-2/PlexinA4 holoreceptor.

Journal of Neurotrauma, Volume 36, Issue 3, Page 411-420, February 1, 2019.

The combinatorial olfactory code conveys odor stimulus features in an entangled manner. Si et al. uncover structure and statistical properties in ORN responses that allow separated representations of odor features and shine light on the mechanism of molecular recognition by olfactory

In nonlinear systems, converging oscillatory inputs undergo frequency mixing, resulting in additional oscillations in the system’s response. Neural recordings exhibit spectral properties predicted by this process suggesting that not all oscillations originate from synaptic inputs rhythmically active at corresponding frequencies.

Recent studies have queried the role of netrin1 from floor plate (FP-netrin1) in guiding commissural axons. Wu et al. show that, in spinal cord, FP-netrin1 is required and acts at long range to guide commissural axons, collaborating with Shh.

The global burden of epilepsy is huge. In 2016, 45·9 million people worldwide were reported to have epilepsy, and epilepsy accounted for 126 055 deaths and 13·5 million disability-adjusted life-years. Although around 70% of patients with epilepsy respond to antiepileptic drugs,

‘Rules are for the obedience of fools and the guidance of wise men’. Douglas Bader Group Captain Sir Douglas Bader was a fighter pilot who returned to flying despite having lost both legs in a crash. He was famously determined

We need greater vigilance, with more rigid or standard criteria for atypical CIDP Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated neuropathy progressive for more than 2 months, including several clinical subtypes.1 2 In 1975, Dyck et al3 described the

Lee et al. examine the functional synaptic organization of callosal projections onto layer 2/3 pyramidal neurons in the primary visual cortices of mice. They find that callosal and intra-cortical inputs with similar orientation preference cluster together on short dendritic segments.

Budelli et al. find Drosophila thermoregulatory behavior is driven by a combination of heating and cooling detectors rather than hot- and cold-labeled lines. They further show Ionotropic Receptors not only confer thermosensitivity but also specify the thermoreceptor’s complex dendritic morphology.

Presentation of Case. Dr. Timothy J. Petersen: A 34-year-old man was evaluated at this hospital because of headaches, cognitive changes, mood symptoms, flashbacks, chest pain, arm tingling, and gastrointestinal symptoms. The patient had served as a special operations combat medic

Cheng et al. show that decreased expression and function of HCN2 channels cause reduced ChI tonic activity in NAc shell that leads to depressive phenotypes. Targeting HCN2 channels to enhance ChI activity is sufficient to rescue depression.

cTag-CLIP provides a next-generation strategy to profile functional protein:RNA interactions at cell-specific resolution in vivo. Saito et al. show that differential NOVA2 regulatory actions on alternative splicing coupled to intron removal in different neurons.

The relationship between LFP patterns and single-neuron firing in the visual cortex is identified by Senzai et al. by using high-density silicon probe recordings, ICA-based LFP analysis, LFP-spike coupling, and spike transmission probability in freely moving mice.

Diseases as different as spinal muscular atrophy and hyperlipidemias can now be treated with drugs that act on RNA. A new class of drugs — oligonucleotides — takes advantage of Watson and Crick’s base-pairing rules to target disease-related RNAs. With

Li et al. generate high-resolution single-cell transcriptomes of microglia and related myeloid cells across mouse brain regions and developmental stages. They show limited heterogeneity of adult microglia and identify an early postnatal phagocytic subset of proliferative-region-associated microglia (PAM).

Journal of Neurotrauma, Volume 36, Issue 2, Page 189-189, January 15, 2019.

Neuner et al. describe the generation and validation of the AD-BXDs, the first reproducible set of AD mouse models incorporating genetic diversity. These models recapitulate aspects of human AD and provide a new resource to identify genes and pathways associated with

Every January issue of The Lancet Neurology includes a special Round Up section. Its pages are a celebration of research achievements over the previous year. Our 2018 Round Up reveals a booming specialty, in which the pace of discovery is

Following the initial description of HINTS to diagnose acute vestibular syndrome (AVS) in 2009, there has been significant interest in the systematic evaluation of HINTs to diagnose stroke and other less common central causes of AVS. This trend increased with

Following the initial description of HINTS to diagnose acute vestibular syndrome (AVS) in 2009, there has been significant interest in the systematic evaluation of HINTs to diagnose stroke and other less common central causes of AVS. This trend increased with

Neuroinflammation contributes to ALS and FTD pathophysiology The pathophysiological mechanisms underlying the development of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) remain to be fully elucidated, although overlapping biological processes expressed in different proportions in neuronal and non-neuronal cells

Variable rates of diagnosis and treatment of attention deficit–hyperactivity disorder (ADHD) across the United States have aroused concern about overdiagnosis, underdiagnosis, and appropriate treatment. Over the past two decades, rates of diagnosis and treatment of ADHD have increased. Among…

A 56-year-old woman presented to the emergency department with a 1-week history of frontotemporal headaches and nausea. She also noted mild upper respiratory symptoms and cough, which she had treated with codeine. When her headaches had progressed to what she

When I imagined this moment, I always thought that it would crush me. Dad stared at me and then back at the social worker. She stood in the doorway, smiling expectantly. She asked again, more loudly than necessary: “Can you

Journal of Neurotrauma, Volume 35, Issue 23, Page 2737-2754, December 1, 2018.

Using ex vivo patch-clamp recordings, optogenetics, and chemogenetics, Williams and Holtmaat dissect the circuits underlying sensory-driven LTP in the cortex. This reveals a circuit motif in which higher-order thalamocortical input gates plasticity of intracortical synapses via VIP-mediated disinhibition.

Sato Y, Asoh T, Metoki N, et al. Efficacy of methylprednisolone pulse therapy on neuroleptic malignant syndrome in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003;74:574–576. This article has been retracted. The editor received a letter from Dr Yoshihiro Sato retracting this article

Xu et al. demonstrate that DIP-α and Dpr6/10 heterophilic and DIP-α homophilic interactions regulate multiple aspects of circuit assembly including layer-specific targeting, cell survival, and synapse number and distribution in the Drosophila visual system.

Artificial intelligence promises to provide innovations for many aspects of life in the 21st century, from unbeatable chess players and self-driving cars to smart houses. We can anticipate it will improve healthcare. The exponential growth of computing power makes machine

Ponce-Alvarez et al. show that zebrafish larvae generate spontaneous neuronal avalanches across the entire brain. These collective cascading events exhibit scale invariance, typical of critical phenomena (e.g., earthquakes, paper crumpling). The brain’s critical dynamics are modulated during interactions with the environment.

Tremendous effort has been dedicated by the research community to further our understanding of the complexities of Alzheimer’s disease. Knowledge that pathological processes start many years before clinical symptoms has highlighted the importance of identifying a disease-modifying drug that can

Hoffman et al. reveal the molecular machinery underlying neurotransmission at a gentle-touch receptor. Employing Eccles’s classical criteria for a chemical synapse, they show that epithelial Merkel cells communicate with sensory neurons through β2-adrenergic receptors at excitatory synapses.

Journal of Neurotrauma, Volume 35, Issue 22, Page 2605-2614, November 15, 2018.

In this study of C. elegans food response behavior, the underlying circuitry is identified by dopaminergic neurons signaling the presence of food to interneurons that release neuropeptides and regulate locomotion by conferring distinct motoneuron responses via specific neuropeptide receptor expression.

To the Editor: Long-duration spaceflight has detrimental effects in several physiological systems. Several studies have shown an upward shift of the cerebral hemispheres, a decrease in frontotemporal volume, and an increase in ventricle size after spaceflight. However, information is limited

Cerebellar functional networks are topographically individual-specific. Cerebellar intrinsic fMRI signals lag those in cortex by 100–400 ms. The frontoparietal control network is greatly overrepresented (>2-fold), suggesting that the cerebellum is important for the adaptive control of the brain’s cognitive processes.

A 32-year-old man presented to the neurosurgery clinic with mild balance difficulties and hearing loss in the left ear. He had a family history of neurofibromatosis type 2 and a diagnosis of tumors in the right and left internal acoustic

Mutations in FUS are causative of ALS and frontotemporal dementia (FTD). López-Erauskin et al. show that disease-causing mutant FUS inhibits intra-axonal protein synthesis and provokes hippocampal synaptic loss and dysfunction without loss of nuclear FUS function or FUS aggregation.

PIEZO1 is an ion channel that converts mechanical stimuli into cellular signaling. Here, Chen et al. perform multi-species studies to define a feedforward circuit mediated by PIEZO1 and tumor tissue mechanics to promote glioma growth.

Harris et al. (2018) demonstrate that neuronal innate immune signaling coordinates the rapid induction and sustained expression of presynaptic homeostatic plasticity. Signaling includes the Map3K Tak1, which directly interfaces with the vesicle release machinery by stabilizing the docked synaptic vesicle state.

Kim et al. show that loss-of-function mutation of the chromatin regulator gene Chd2 produces deficits in neuron proliferation, synaptic function, and memory in mice.

Diaz-Hernández et al. performed electrophysiological recordings of antidromically photo-identified thalamostriatal neurons and optogenetic inhibition of the thalamostriatal terminals to probe their contribution to the smooth initiation and execution of a sequence of movements. Their data support a model in which different

Over history, diseases have appeared and disappeared, or have increased or decreased in frequency. These epidemiological trends have occurred more dramatically for infectious diseases (eg, the eradication of small pox), but have also occurred for chronic diseases (eg, reduction of

Traumatic brain injury (TBI) is a leading cause of death and disability in children worldwide. However, neurological evaluation in children can be difficult and evidence suggests that paediatric patients can have symptoms of injury that differ from those in adult

Most movement disorders specialists will care for only a handful of children with juvenile Huntington’s disease (onset at age 20 years or younger) during a lifetime of clinical practice. Therefore, the retrospective study of 36 children and adolescents with juvenile

In chronic disease, human nature drives the identification of factors that influence the often-fluctuating course. The formerly used term “lunatic” for patients suffering from psychiatric diseases and epilepsy was a reflection of suspected mensual influences associated with the phases of

Migraine is one of the most frequent neurological diseases, but its burden is generally underestimated, mainly because of the transient nature of primary headaches.1,2 In contrast to the perception that migraines are not a cause of substantial burden, migraine, together

To the Editor: Viral encephalitis developed in a previously healthy 25-year-old man, and he died 1 month after the onset of symptoms. He was an engineering student and lived in Central Franconia, Bavaria, Germany, with his family and two dogs