Neuroscience

A common neural circuit mechanism for internally guided and externally reinforced forms of motor learning

Nature Neuroscience - 26 February 2018 - 12:00am

A common neural circuit mechanism for internally guided and externally reinforced forms of motor learning

A common neural circuit mechanism for internally guided and externally reinforced forms of motor learning, Published online: 26 February 2018; doi:10.1038/s41593-018-0092-6

Intersectional gene ablation, pharmacology & song-triggered optogenetic stimulation of VTA terminals together show a common VTA–basal ganglia circuit enabling internally and externally guided juvenile song-copying and adult pitch learning in finches.
Categories: Neuroscience

Feedback determines the structure of correlated variability in primary visual cortex

Nature Neuroscience - 26 February 2018 - 12:00am

Feedback determines the structure of correlated variability in primary visual cortex

Feedback determines the structure of correlated variability in primary visual cortex, Published online: 26 February 2018; doi:10.1038/s41593-018-0089-1

The way spike count variability is correlated between two neurons depends on the neurons' stimulus preferences. Here the authors show that this dependency itself varies systematically with behavioral task, implying a feedback origin of correlations.
Categories: Neuroscience

An innate circuit for object craving

Nature Neuroscience - 23 February 2018 - 12:00am

An innate circuit for object craving

An innate circuit for object craving, Published online: 23 February 2018; doi:10.1038/s41593-018-0087-3

Using a series of functional manipulation and in vivo recording tools, Park et al. identify a pathway from medial preoptic CaMKIIα-expressing neurons to the ventral periaqueductal gray that mediates object craving and prey hunting.
Categories: Neuroscience

Following the pathway to Alzheimer’s disease

Nature Neuroscience - 23 February 2018 - 12:00am

Following the pathway to Alzheimer’s disease

Following the pathway to Alzheimer’s disease, Published online: 23 February 2018; doi:10.1038/s41593-018-0085-5

The human brain shows regional selective vulnerability to the pathology of Alzheimer’s disease. Jacobs et al. show that the protein amyloid-β promotes the spread of tau through specific components of a neural system underlying memory formation, thus leading to the prominent early symptom of amnesia.
Categories: Neuroscience

Stress and sociability

Nature Neuroscience - 23 February 2018 - 12:00am

Stress and sociability

Stress and sociability, Published online: 23 February 2018; doi:10.1038/s41593-018-0088-2

Humans and animals can react to the affective state of others in distress. However, exposure to a stressed partner can trigger stress-related adaptations. Two studies shed light on the mechanisms underlying the behavioral responses toward stressed individuals and on the synaptic changes associated with social transmission of stress.
Categories: Neuroscience

Huntington modeling improves with age

Nature Neuroscience - 23 February 2018 - 12:00am

Huntington modeling improves with age

Huntington modeling improves with age, Published online: 23 February 2018; doi:10.1038/s41593-018-0086-4

Direct conversion of adult Huntington’s disease patient fibroblasts into medium spiny neurons recapitulates hallmark phenotypes such as cell death, in contrast to models that lack epigenetic markers of aging. This successful ‘disease-in-a-dish’ highlights the benefits of capturing age in an adult-onset disorder model.
Categories: Neuroscience

Dorsal root ganglia volume differentiate schwannomatosis and neurofibromatosis 2

Annals of Neurology - 22 February 2018 - 5:10pm
Abstract

Schwannomatosis and neurofibromatosis type 2 are hereditary tumor syndromes and peripheral neuropathy has been reported in both. We prospectively applied in-vivo morphometric measurement of dorsal root ganglia volume in 16 schwannomatosis, 14 neurofibromatosis type 2 patients, and 26 healthy controls by MR-Neurography. Compared to healthy controls, dorsal root ganglia hypertrophy was a consistent finding in neurofibromatosis type 2 (L3: +267%, L4: +235%, L5: +241%, S1: +300% and S2: +242%, Bonferroni-adjusted p<0.001) but not in schwannomatosis. Dorsal root ganglia may be a vulnerable site in origination of areflexia and sensory loss and a useful diagnostic marker in neurofibromatosis type 2. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

Seizures and disturbed brain potassium dynamics in the leukodystrophy MLC

Annals of Neurology - 22 February 2018 - 12:00am
ABSTRACT

Objective: Loss of function of the astrocyte-specific protein MLC1 leads to the childhood onset leukodystrophy “megalencephalic leukoencephalopathy with subcortical cysts” (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking.

Methods: We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole cell patch-clamp recordings and K+-sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC.

Results: An early onset of seizures is common in MLC. Similarly, in MLC mice we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of individual pyramidal neurons are unchanged, extracellular K+ dynamics and neuronal network activity are abnormal in MLC mice.

Interpretation: Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures. These findings suggest a role for defective astrocyte volume regulation in epilepsy. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion

Nature Neuroscience - 22 February 2018 - 12:00am

Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion

Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion, Published online: 22 February 2018; doi:10.1038/s41593-018-0090-8

Microglia show remarkable regenerative capacity after acute depletion, which had been thought to be derived from de novo progenitors. Peng and colleagues demonstrate that the newly formed microglia are actually solely derived from residual microglia.
Categories: Neuroscience

Signalling from the periphery to the brain that regulates energy homeostasis

Nature Rev. Neurosc. - 22 February 2018 - 12:00am

Signalling from the periphery to the brain that regulates energy homeostasis

Signalling from the periphery to the brain that regulates energy homeostasis, Published online: 22 February 2018; doi:10.1038/nrn.2018.8

Coordination between peripheral signals that reflect feeding status and central regulatory mechanisms are crucial for regulating body weight. In this Review, Sandoval and colleagues discuss how and where peripherally derived signals are integrated within the CNS to modulate feeding behaviour.
Categories: Neuroscience

Emotion: 'Anxiety cells' drive avoidance

Nature Rev. Neurosc. - 22 February 2018 - 12:00am

Emotion: 'Anxiety cells' drive avoidance

Emotion: 'Anxiety cells' drive avoidance, Published online: 22 February 2018; doi:10.1038/nrn.2018.21

A population of 'anxiety cells' that encode anxiogenic information and drive avoidance behaviour is identified in the mouse hippocampus.
Categories: Neuroscience

Mutations in SCN3A cause early infantile epileptic encephalopathy

Annals of Neurology - 21 February 2018 - 11:50pm
Abstract

Objective: Voltage-gated sodium (Na+) channels underlie action potential generation and propagation and hence are central to the regulation of excitability in the nervous system. Mutations in the genes SCN1A, SCN2A, and SCN8A, encoding the Na+ channel pore-forming (α) subunits Nav1.1, 1.2, and 1.6, respectively, and SCN1B, encoding the accessory subunit β1, are established causes of genetic epilepsies. SCN3A, encoding Nav1.3, is known to be highly expressed in brain, but has not previously been linked to early infantile epileptic encephalopathy. Here, we describe a cohort of four patients with epileptic encephalopathy and heterozygous de novo missense variants in SCN3A (p.Ile875Thr in two cases, p.Pro1333Leu, and p.Val1769Ala).

Methods: All patients presented with treatment-resistant epilepsy in the first year of life, severe to profound intellectual disability, and, in two cases (both with the variant p.Ile875Thr), diffuse polymicrogyria.

Results: Electrophysiological recordings of mutant channels revealed prominent gain of channel function, with a markedly increased amplitude of the slowly inactivating current component, and, for two of three mutants (p.Ile875Thr and p.Pro1333Leu), a left-shift in the voltage dependence of activation to more hyperpolarized potentials. Gain of function was not observed for Nav1.3 variants known or presumed to be inherited (p.Arg1642Cys and p.Lys1799Gln). The anti-seizure medications phenytoin and lacosamide selectively blocked slowly inactivating over transient current in wild-type and mutant Nav1.3 channels.

Interpretation: These findings establish SCN3A as a new gene for infantile epileptic encephalopathy and suggest a potential pharmacologic intervention. These findings also reinforce the role of Nav1.3 as an important regulator of neuronal excitability in the developing brain while providing additional insight into mechanisms of slow inactivation of Nav1.3. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

Memory Complaints, Dementia, and Neuropathology in Older Blacks and Whites

Annals of Neurology - 21 February 2018 - 11:50pm
ABSTRACT

Objective: To determine relationships of memory complaints to cognitive function and decline, incident dementia, and neurodegenerative and other neuropathologies, as well as the population-attributable risk for dementia in older black and white persons.

Methods: 4015 community-based persons (28% black; 74% women; mean baseline age 78 years), were enrolled in one of four longitudinal cohort studies, and another 2937 in a population-based cohort. Memory scores, assessed using two questions (5-point Likert scales) were categorized as complaints present or absent. Global cognition and five cognitive domains were derived from annual neuropsychological tests. Dementia was assessed from these tests and additional data. Neuropathologic data were available for 1350 deceased with brain autopsies. Regression and mixed effects models were used to examine relationships of memory complaints to cognition and neuropathology.

Results: Baseline memory complaints (n=1310; 33% of 4015) were associated with lower cognition and faster decline in all domains (global score estimate = -0.032 [SE=0.004], p<0.0001), during a mean follow-up of 6 (SD=2) years. Persons with memory complaints had higher dementia risk (HR=1.64; 95%CI: 1.42-1.89) and odds of pathologic Alzheimer's disease (OR=1.96; 95%CI: 1.51-2.54), neocortical Lewy bodies (OR=2.47, 95%CI: 1.54-3.96), and other neurodegenerative pathologies. Results for dementia risk were similar among blacks and whites. Among 2937 older persons in a population-based cohort with similar data, the population-attributable risk for incident dementia due to memory complaints was 14.0% (95%CI: 2.6-23.0), and did not vary between the black and white groups.

Interpretation: Memory complaints are common in older black and white persons, and relate to cognitive decline, dementia risk, and neurodegenerative pathologies. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

Issue Information - Copyright

Annals of Neurology - 21 February 2018 - 5:18am
Categories: Neuroscience

Issue Information - Masthead

Annals of Neurology - 21 February 2018 - 5:18am
Categories: Neuroscience

Annals of Neurology: Volume 83, Number 2, February 2018

Annals of Neurology - 21 February 2018 - 5:17am

A raster display of repeated motor cortical evoked potentials with single pulses of deep brain stimulation in the globus pallidus, pars interna in a patient with cervical dystonia. Each line represents a single trial, with stimulation beginning at the left margin, and the length of each line equivalent to 50 msec of recording. Dark blue = 0 mV, lighter blue-green colors = negative voltage, purple-red colors = positive voltage. Note that the evoked potential is negative at about 10 msec, positive at about 25 msec, and then near zero again at 50 msec. See Ni et al., pp 352–362, this issue. Ann Neurol 2018;83:1–1

Categories: Neuroscience

Issue Information - TOC

Annals of Neurology - 21 February 2018 - 5:17am
Categories: Neuroscience

Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia

Annals of Neurology - 20 February 2018 - 4:45pm
ABSTRACT

Objective: Focal cortical dysplasias (FCDs) are an important cause of drug-resistant epilepsy. In this work we aimed to investigate whether abnormal gene regulation, mediated by microRNA, could be involved in FCD type II.

Methods: We used total RNA from the brain tissue of 16 patients with FCD type II and 28 controls. MicroRNA expression was initially assessed by microarray. Quantitative PCR (qPCR), in situ hybridization, luciferase reporter assays and deep sequencing for genes in the mTOR pathway were performed to validate and further explore our initial study.

Results: hsa-let-7f (p=0.039), hsa-miR-31 (p=0.0078) and hsa-miR34a (p=0.021) were downregulated in FCD type II, whereas a transcription factor involved in neuronal and glial fate specification, NEUROG2 (p<0.05), was upregulated. We also found that the RND2 gene, a NEUROG2-target, is upregulated (p<0.001). In vitro experiments showed that hsa-miR-34a downregulates NEUROG2 by binding to its 5'-untranslated region. Moreover, we observed strong nuclear expression of NEUROG2 in balloon cells and dysmorphic neurons and found that 28.5% of our patients presented brain somatic mutations in genes of the mTOR pathway.

Interpretation: Our findings suggest a new molecular mechanism, in which NEUROG2 has a pivotal and central role in the pathogenesis of FCD type II. In this way, we found that the downregulation of hsa-miR-34a leads to upregulation of NEUROG2, and consequently to overexpression of the RND2 gene. These findings indicate that a faulty coupling in neuronal differentiation and migration mechanisms may explain the presence of aberrant cells and complete dyslamination in FCD type II. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

Microglia-mediated recovery from ALS-relevant motor neuron degeneration in a mouse model of TDP-43 proteinopathy

Nature Neuroscience - 20 February 2018 - 12:00am

Microglia-mediated recovery from ALS-relevant motor neuron degeneration in a mouse model of TDP-43 proteinopathy

Microglia-mediated recovery from ALS-relevant motor neuron degeneration in a mouse model of TDP-43 proteinopathy, Published online: 20 February 2018; doi:10.1038/s41593-018-0083-7

Using an inducible mouse model of sporadic ALS, Spiller et al. show that spinal microgliosis is not a major feature of TDP-43-triggered disease. Instead, microglia mediate TDP-43 clearance and motor recovery, suggesting a neuroprotective role in ALS.
Categories: Neuroscience

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