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https://www.readbyqxmd.com/read/28742811/decreased-rhes-mrna-levels-in-the-brain-of-patients-with-parkinson-s-disease-and-mptp-treated-macaques
#1
Francesco Napolitano, Emily Booth Warren, Sara Migliarini, Daniela Punzo, Francesco Errico, Qin Li, Marie-Laure Thiolat, Angelo Luigi Vescovi, Paolo Calabresi, Erwan Bezard, Micaela Morelli, Christine Konradi, Massimo Pasqualetti, Alessandro Usiello
In rodent and human brains, the small GTP-binding protein Rhes is highly expressed in virtually all dopaminoceptive striatal GABAergic medium spiny neurons, as well as in large aspiny cholinergic interneurons, where it is thought to modulate dopamine-dependent signaling. Consistent with this knowledge, and considering that dopaminergic neurotransmission is altered in neurological and psychiatric disorders, here we sought to investigate whether Rhes mRNA expression is altered in brain regions of patients with Parkinson's disease (PD), Schizophrenia (SCZ), and Bipolar Disorder (BD), when compared to healthy controls (about 200 post-mortem samples)...
2017: PloS One
https://www.readbyqxmd.com/read/28740469/neuroligins-nlg2-and-nlg4-affect-social-behavior-in-drosophila-melanogaster
#2
Kristina Corthals, Alina Sophia Heukamp, Robert Kossen, Isabel Großhennig, Nina Hahn, Heribert Gras, Martin C Göpfert, Ralf Heinrich, Bart R H Geurten
The genome of Drosophila melanogaster includes homologs to approximately one-third of the currently known human disease genes. Flies and humans share many biological processes, including the principles of information processing by excitable neurons, synaptic transmission, and the chemical signals involved in intercellular communication. Studies on the molecular and behavioral impact of genetic risk factors of human neuro-developmental disorders [autism spectrum disorders (ASDs), schizophrenia, attention deficit hyperactivity disorders, and Tourette syndrome] increasingly use the well-studied social behavior of D...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28737061/functional-and-structural-alterations-in-the-migraine-cerebellum
#3
Jan Mehnert, Arne May
The cerebellum plays an important role in pain processing but its function in headache and specifically in migraine is not known. We therefore compared 54 migraineurs with pairwise matched healthy controls in a magnetic resonance imaging study on neuronal cerebellar activity in response to nociceptive trigeminal sensation and also investigated possible structural alterations. Headache frequency, disease duration, and the proximity to a migraine attack were used as co-factors. Migraine patients showed functional and structural alterations in the posterior part of the cerebellum, namely crus I and crus II...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28736520/combined-effects-of-feedforward-inhibition-and-excitation-in-thalamocortical-circuit-on-the-transitions-of-epileptic-seizures
#4
Denggui Fan, Lixia Duan, Qian Wang, Guoming Luan
The mechanisms underlying electrophysiologically observed two-way transitions between absence and tonic-clonic epileptic seizures in cerebral cortex remain unknown. The interplay within thalamocortical network is believed to give rise to these epileptic multiple modes of activity and transitions between them. In particular, it is thought that in some areas of cortex there exists feedforward inhibition from specific relay nucleus of thalamus (TC) to inhibitory neuronal population (IN) which has even more stronger functions on cortical activities than the known feedforward excitation from TC to excitatory neuronal population (EX)...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/28736137/nogo-presence-is-inversely-associated-with-shifts-in-cortical-microglial-morphology-following-experimental-diffuse-brain-injury
#5
Jenna M Ziebell, Helen Ray-Jones, Jonathan Lifshitz
Diffuse traumatic brain injury (TBI) initiates secondary pathology, including inflammation and reduced myelination. Considering these injury-related pathologies, the many states of activated microglia as demonstrated by differing morphologies would form, migrate, and function in and through fields of growth-inhibitory myelin byproduct, specifically Nogo. Here we evaluate the relationship between inflammation and reduced myelin antigenicity in the wake of diffuse TBI and present the hypothesis that the Nogo-66 receptor antagonist peptide NEP(1-40) would reverse the injury-induced shift in distribution of microglia morphologies by limiting myelin-based inhibition...
July 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/28735749/initiation-of-behavioral-response-to-antidepressants-by-cholecystokinin-neurons-of-the-dentate-gyrus
#6
Lucian Medrihan, Yotam Sagi, Zintis Inde, Oleh Krupa, Chelsea Daniels, Adrien Peyrache, Paul Greengard
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used class of antidepressant drugs, but the cellular and molecular mechanisms by which their therapeutic action is initiated are poorly understood. Here we show that serotonin 5-HT1B receptors in cholecystokinin (CCK) inhibitory interneurons of the mammalian dentate gyrus (DG) initiate the therapeutic response to antidepressants. In these neurons, 5-HT1B receptors are expressed presynaptically, and their activation inhibits GABA release. Inhibition of GABA release from CCK neurons disinhibits parvalbumin (PV) interneurons and, as a consequence, reduces the neuronal activity of the granule cells...
July 19, 2017: Neuron
https://www.readbyqxmd.com/read/28735746/parallel-inhibitory-and-excitatory-trigemino-facial-feedback-circuitry-for-reflexive-vibrissa-movement
#7
Marie-Andrée Bellavance, Jun Takatoh, Jinghao Lu, Maxime Demers, David Kleinfeld, Fan Wang, Martin Deschênes
Animals employ active touch to optimize the acuity of their tactile sensors. Prior experimental results and models lead to the hypothesis that sensory inputs are used in a recurrent manner to tune the position of the sensors. A combination of electrophysiology, intersectional genetic viral labeling and manipulation, and classical tracing allowed us to identify second-order sensorimotor loops that control vibrissa movements by rodents. Facial motoneurons that drive intrinsic muscles to protract the vibrissae receive a short latency inhibitory input, followed by synaptic excitation, from neurons located in the oralis division of the trigeminal sensory complex...
July 13, 2017: Neuron
https://www.readbyqxmd.com/read/28735013/simultaneous-intrinsic-signal-imaging-of-auditory-and-visual-cortex-reveals-profound-effects-of-acute-hearing-loss-on-visual-processing
#8
Manuel Teichert, Jürgen Bolz
It has been suggested that primary sensory cortices do not work in isolation but receive subthreshold inputs originating from other senses. However, repercussions of an acute loss of one sense on multimodal sensory processing remain elusive. Here we investigated the early effects of acute hearing loss on visual processing in adult mice. For this, we developed a method to simultaneously map the primary auditory (A1) and visual cortex (V1) using periodic intrinsic optical imaging. We found that reducing sound evoked A1 responsiveness due to the induction of conductive hearing loss (CHL) led to a concomitant increase of visually driven V1 activity...
July 19, 2017: NeuroImage
https://www.readbyqxmd.com/read/28734869/p2x-receptors-up-regulate-the-cell-surface-expression-of-the-neuronal-glycine-transporter-glyt2
#9
Lucía Villarejo-López, Esperanza Jiménez, David Bartolomé-Martín, Francisco Zafra, Pablo Lapunzina, Carmen Aragón, Beatriz López-Corcuera
Glycinergic inhibitory neurons of the spinal dorsal horn exert critical control over the conduction of nociceptive signals to higher brain areas. The neuronal glycine transporter 2 (GlyT2) is involved in the recycling of synaptic glycine from the inhibitory synaptic cleft and its activity modulates intra and extracellular glycine concentrations. In this report we show that the stimulation of P2X purinergic receptors with βγ-methylene adenosine 5'-triphosphate induces the up-regulation of GlyT2 transport activity by increasing total and plasma membrane expression and reducing transporter ubiquitination...
July 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28734725/estrogen-receptor-alpha-is-required-in-gabaergic-but-not-glutamatergic-neurons-to-masculinize-behavior
#10
Melody V Wu, Jessica Tollkuhn
Masculinization of the altricial rodent brain is driven by estrogen signaling during a perinatal critical period. Genetic deletion of estrogen receptor alpha (Esr1/ERα) results in altered hypothalamic-pituitary-gonadal (HPG) axis signaling and a dramatic reduction of male sexual and territorial behaviors. However, the role of ERα in masculinizing distinct classes of neurons remains unexplored. We deleted ERα in excitatory or inhibitory neurons using either a Vglut2 or Vgat driver and assessed male behaviors...
July 20, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28733833/neuroanatomy-of-pain-deficiency-and-cross-modal-activation-in-calcium-channel-subunit-cacn-%C3%AE-2%C3%AE-3-knockout-mice
#11
Julia Landmann, Franziska Richter, Ana-Maria Oros-Peusquens, N Jon Shah, Joseph Classen, G Gregory Neely, Angelika Richter, Josef M Penninger, Ingo Bechmann
The phenotype of calcium channel subunit (CACN) α2δ3 knockout (KO) mice includes sensory cross-activation and deficient pain perception. Sensory cross-activation defines the activation of a sensory cortical region by input from another modality due to reorganization in the brain such as after sensory loss. To obtain mechanistic insight into both phenomena, we employed a comprehensive battery of neuroanatomical techniques. While CACNα2δ3 was ubiquitously expressed in wild-type mice, it was absent in α2δ3 KO animals...
July 21, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28733354/selective-silencing-of-hippocampal-parvalbumin-interneurons-induces-development-of-recurrent-spontaneous-limbic-seizures-in-mice
#12
Meinrad Drexel, Roman A Romanov, James Wood, Stefan Weger, Regine Heilbronn, Peer Wulff, Ramon O Tasan, Tibor Harkany, Günther Sperk
Temporal lobe epilepsy (TLE) is the most frequent form of focal epilepsies and generally associated with malfunctioning of the hippocampal formation. Recently, a preferential loss of parvalbumin (PV) neurons has been observed in the subiculum of TLE patients and in animal models of TLE. To demonstrate a possible causative role of defunct PV neurons in the generation of TLE, we permanently inhibited GABA release selectively from PV neurons of the ventral subiculum by injecting a viral vector expressing tetanus toxin light chain in male mice...
July 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28729159/what-do-we-know-about-laminar-connectivity
#13
REVIEW
Kathleen S Rockland
In this brief review, I attempt an overview of the main components of anatomical laminar-level connectivity. These are: extrinsic outputs, excitatory and inhibitory intrinsic connectivity, and intrinsic inputs. Supporting data are biased from the visual system of nonhuman primates (NHPs), but I have drawn as much as possible from a broader span in order to treat the important issue of area-specific variability. In a second part, I briefly discuss laminar connectivity in the context of network organization (feedforward/feedback cortical connections, and the major types of corticothalamic connections)...
July 17, 2017: NeuroImage
https://www.readbyqxmd.com/read/28728108/new-tacrine-dimers-with-antioxidant-linkers-as-dual-drugs-anti-alzheimer-s-and-antiproliferative-agents
#14
Jesús M Roldán-Peña, Daniel Alejandre-Ramos, Óscar López, Inés Maya, Irene Lagunes, José M Padrón, Luis Emiliano Peña-Altamira, Manuela Bartolini, Barbara Monti, Maria L Bolognesi, José G Fernández-Bolaños
We have designed a series of tacrine-based homo- and heterodimers that incorporate an antioxidant tether (selenoureido, chalcogenide) as new dual compounds: for the treatment of Alzheimer's disease and as antiproliferative agents. Symmetrical homodimers bearing a dichalcogenide or selenide-based tether, the best compounds in the series, were found to be strong and highly selective electric eel AChE inhibitors, with inhibition constants within the low nanomolar range. This high inhibitory activity was confirmed on recombinant human AChE for the most interesting derivatives...
June 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28727685/erbb4-signaling-in-dopaminergic-axonal-projections-increases-extracellular-dopamine-levels-and-regulates-spatial-working-memory-behaviors
#15
M Skirzewski, I Karavanova, A Shamir, L Erben, J Garcia-Olivares, J H Shin, D Vullhorst, V A Alvarez, S G Amara, A Buonanno
Genetic variants of Neuregulin 1 (NRG1) and its neuronal tyrosine kinase receptor ErbB4 are associated with risk for schizophrenia, a neurodevelopmental disorder characterized by excitatory/inhibitory imbalance and dopamine (DA) dysfunction. To date, most ErbB4 studies have focused on GABAergic interneurons in the hippocampus and neocortex, particularly fast-spiking parvalbumin-positive (PV+) basket cells. However, NRG has also been shown to modulate DA levels, suggesting a role for ErbB4 signaling in dopaminergic neuron function...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28726769/activity-dependent-feedback-inhibition-may-maintain-head-direction-signals-in-mouse-presubiculum
#16
Jean Simonnet, Mérie Nassar, Federico Stella, Ivan Cohen, Bertrand Mathon, Charlotte N Boccara, Richard Miles, Desdemona Fricker
Orientation in space is represented in specialized brain circuits. Persistent head direction signals are transmitted from anterior thalamus to the presubiculum, but the identity of the presubicular target neurons, their connectivity and function in local microcircuits are unknown. Here, we examine how thalamic afferents recruit presubicular principal neurons and Martinotti interneurons, and the ensuing synaptic interactions between these cells. Pyramidal neuron activation of Martinotti cells in superficial layers is strongly facilitating such that high-frequency head directional stimulation efficiently unmutes synaptic excitation...
July 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28723570/dynamic-control-of-dendritic-mrna-expression-by-cnot7-regulates-synaptic-efficacy-and-higher-cognitive-function
#17
Rhonda L McFleder, Fernanda Mansur, Joel D Richter
Translation of mRNAs in dendrites mediates synaptic plasticity, the probable cellular basis of learning and memory. Coordination of translational inhibitory and stimulatory mechanisms, as well as dendritic transport of mRNA, is necessary to ensure proper control of this local translation. Here, we find that the deadenylase CNOT7 dynamically regulates dendritic mRNA translation and transport, as well as synaptic plasticity and higher cognitive function. In cultured hippocampal neurons, synaptic stimulation induces a rapid decrease in CNOT7, which, in the short-term, results in poly(A) tail lengthening of target mRNAs...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723268/assay-of-calcium-transients-and-synapses-in-rat-hippocampal-neurons-by-kinetic-image-cytometry-and-high-content-analysis-an-in-vitro-model-system-for-postchemotherapy-cognitive-impairment
#18
Patrick M McDonough, Natalie L Prigozhina, Ranor C B Basa, Jeffrey H Price
Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days...
July 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28722246/delta-9-tetrahydrocannabinol-decreases-masticatory-muscle-sensitization-in-female-rats-through-peripheral-cannabinoid-receptor-activation
#19
H Wong, S Hossain, B E Cairns
BACKGROUND: This study investigated whether intramuscular injection of delta-9-tetrahydrocannabinol (THC), by acting on peripheral cannabinoid (CB) receptors, could decrease nerve growth factor (NGF)-induced sensitization in female rat masseter muscle; a model which mimics the symptoms of myofascial temporomandibular disorders. METHODS: Immunohistochemistry was used to explore the peripheral expression of cannabinoid receptors in the masseter muscle while behavioural and electrophysiology experiments were employed to assess the functional effects of intramuscular injection of THC...
July 18, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28720882/cell-type-specific-differences-in-promoter-activity-of-the-als-linked-c9orf72-mouse-ortholog
#20
Abraham J Langseth, Juhyun Kim, Janet E Ugolino, Yajas Shah, Ho-Yon Hwang, Jiou Wang, Dwight E Bergles, Solange P Brown
A hexanucleotide repeat expansion in the C9orf72 gene is the most common cause of inherited forms of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Both loss-of-function and gain-of-function mechanisms have been proposed to underlie this disease, but the pathogenic pathways are not fully understood. To better understand the involvement of different cell types in the pathogenesis of ALS, we systematically analyzed the distribution of promoter activity of the mouse ortholog of C9orf72 in the central nervous system...
July 18, 2017: Scientific Reports
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