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https://www.readbyqxmd.com/read/28729159/what-do-we-know-about-laminar-connectivity
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28720702/identification-of-a-vesicular-atp-release-inhibitor-for-the-treatment-of-neuropathic-and-inflammatory-pain
#9
Yuri Kato, Miki Hiasa, Reiko Ichikawa, Nao Hasuzawa, Atsushi Kadowaki, Ken Iwatsuki, Kazuhiro Shima, Yasuo Endo, Yoshiro Kitahara, Tsuyoshi Inoue, Masatoshi Nomura, Hiroshi Omote, Yoshinori Moriyama, Takaaki Miyaji
Despite the high incidence of neuropathic and inflammatory pain worldwide, effective drugs with few side effects are currently unavailable for the treatment of chronic pain. Recently, researchers have proposed that inhibitors of purinergic chemical transmission, which plays a key role in the pathological pain response, may allow for targeted treatment of pathological neuropathic and inflammatory pain. However, such therapeutic analgesic agents have yet to be developed. In the present study, we demonstrated that clodronate, a first-generation bisphosphonate with comparatively fewer side effects than traditional treatments, significantly attenuates neuropathic and inflammatory pain unrelated to bone abnormalities via inhibition of vesicular nucleotide transporter (VNUT), a key molecule for the initiation of purinergic chemical transmission...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28717877/temporal-envelope-coding-by-inferior-colliculus-neurons-with-cochlear-implant-stimulation
#10
Kenneth E Hancock, Yoojin Chung, Martin F McKinney, Bertrand Delgutte
Modulations in temporal envelopes are a ubiquitous property of natural sounds and are especially important for hearing with cochlear implants (CIs) because these devices typically discard temporal fine structure information. With few exceptions, neural temporal envelope processing has been studied in both normal hearing (NH) and CI animals using only pure sinusoidal amplitude modulation (SAM) which poorly represents the diversity of envelope shapes contained in natural sounds because it confounds repetition rate and the width of each modulation cycle...
July 17, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28716844/microglia-control-the-glycinergic-but-not-the-gabaergic-synapses-via-prostaglandin-e2-in-the-spinal-cord
#11
Yasmine Cantaut-Belarif, Myriam Antri, Rocco Pizzarelli, Sabrina Colasse, Ilaria Vaccari, Sylvia Soares, Marianne Renner, Radhouane Dallel, Antoine Triller, Alain Bessis
Microglia control excitatory synapses, but their role in inhibitory neurotransmission has been less well characterized. Herein, we show that microglia control the strength of glycinergic but not GABAergic synapses via modulation of the diffusion dynamics and synaptic trapping of glycine (GlyR) but not GABAA receptors. We further demonstrate that microglia regulate the activity-dependent plasticity of glycinergic synapses by tuning the GlyR diffusion trap. This microglia-synapse cross talk requires production of prostaglandin E2 by microglia, leading to the activation of neuronal EP2 receptors and cyclic adenosine monophosphate-dependent protein kinase...
July 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28714852/the-small-molecule-mimetic-agonist-trimebutine-of-adhesion-molecule-l1-contributes-to-functional-recovery-after-spinal-cord-injury-in-mice
#12
Junping Xu, Chengliang Hu, Qiong Jiang, Hongchao Pan, Huifan Shen, Melitta Schachner
Curing spinal cord injury (SCI) in mammals is a daunting task because of the lack of permissive mechanisms and strong inhibitory responses at and around the lesion. The neural cell adhesion molecule L1CAM (L1) has been shown to favor axonal regrowth and enhance neuronal survival and synaptic plasticity, and thus constitutes a viable target to promote regeneration after SCI. Since delivery of full-length L1 or its extracellular domain could encounter difficulties in translation to therapy in humans, we have identified several small organic compounds that bind to L1 and stimulate neuronal survival, neuronal migration, and neurite outgrowth in an L1-dependent manner...
July 14, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28714715/the-development-of-perineuronal-nets-around-parvalbumin-gabaergic-neurons-in-the-medial-prefrontal-cortex-and-basolateral-amygdala-of-rats
#13
Kathryn D Baker, Arielle R Gray, Rick Richardson
Perineuronal nets (PNNs) are extracellular matrix structures that preferentially surround mature GABAergic neurons that express the calcium-binding protein parvalbumin (PV). It has been suggested that aberrant PNN formation in humans may contribute to psychological disorders, many of which emerge during childhood and adolescence. The present experiment investigated the normative developmental trajectory of PNN formation in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) in juvenile (P24), adolescent (P35-36), and adult (∼P70) rats...
August 2017: Behavioral Neuroscience
https://www.readbyqxmd.com/read/28714389/a-peptide-based-pro-drug-ameliorates-amyloid-%C3%AE-induced-neuronal-apoptosis-in-in-vitro-sh-sy5y-cells
#14
Sourav Kumar, Ashim Paul, Sourav Kalita, Awanish Kumar, Saurabh Srivastav, Somoday Hazra, Anup Kumar Ghosh, Bhubaneswar Mandal, Amal Chandra Mondal
BACKGROUND: Alzheimer's disease (AD), a common protein misfolding neurodegenerative disorder, is one of the most common forms of dementia. Amyloid precursor protein (APP) derived amyloid-β (Aβ) proteins accumulated into interneuronal spaces and plays a crucial role in the disease progression and its pathology. The aggregated Aβ exerts its neurotoxic effects by inducing apoptosis and oxidative damage in neuronal cells. OBJECTIVES: We have investigated the effects of a synthesized Pro-Drug peptide (PDp) on Aβ1-40 induced cytotoxicity in human neuroblastoma SH-SY5Y cells, represents one of the most effective strategies in combating human AD...
July 13, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28714277/free-fatty-acid-receptor-3-activation-suppresses-neurogenic-motility-in-rat-proximal-colon
#15
I Kaji, Y Akiba, T Furuyama, D W Adelson, K Iwamoto, M Watanabe, A Kuwahara, J D Kaunitz
BACKGROUND: Short-chain fatty acids (SCFA) are microbial fermentation products absorbed by the colon. We recently reported that activation of the SCFA receptor termed free fatty acid receptor 3 (FFA3), expressed on cholinergic nerves, suppresses nicotinic acetylcholine receptor (nAChR)-mediated transepithelial anion secretion. This study aimed to clarify how activation of neurally expressed FFA3 affects colonic motor function. METHODS: FFA3-expressing myenteric neurons were identified by immunostaining; contractions of isolated circular muscle strips obtained from rat proximal colon were measured by isometric transducers...
July 17, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28714144/cerebellins-are-differentially-expressed-in-selective-subsets-of-neurons-throughout-the-brain
#16
Erica Seigneur, Thomas C Südhof
Cerebellins are secreted hexameric proteins that form tripartite complexes with the presynaptic cell-adhesion molecules neurexins or 'deleted-in-colorectal-cancer' (DCC), and the postsynaptic glutamate-receptor-related proteins GluD1 and GluD2. These tripartite complexes are thought to regulate synapses. However, cerebellins are expressed in multiple isoforms whose relative distributions and overall functions are not understood. Three of the four cerebellins, Cbln1, Cbln2, and Cbln4, autonomously assemble into homohexamers, whereas the Cbln3 requires Cbln1 for assembly and secretion...
July 16, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28712684/cerebellar-perineuronal-nets-in-cocaine-induced-pavlovian-memory-site-matters
#17
Maria Carbo-Gas, Josep Moreno-Rius, Julian Guarque-Chabrera, Dolores Vazquez-Sanroman, Isis Gil-Miravet, Daniela Carulli, Freek Hoebeek, Chris De Zeeuw, Carla Sanchis-Segura, Marta Miquel
One of the key mechanisms for the stabilization of synaptic changes near the end of critical periods for experience-dependent plasticity is the formation of specific lattice extracellular matrix structures called perineuronal nets (PNNs). The formation of drug memories depends on local circuits in the cerebellum, but it is unclear to what extent it may also relate to changes in their PNN. Here, we investigated changes in the PNNs of the cerebellum following cocaine-induced preference conditioning. The formation of cocaine-related preference memories increased expression of PNN-related proteins surrounding Golgi inhibitory interneurons as well as that of cFos in granule cells at the apex of the cerebellar cortex...
July 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28711601/catecholaminergic-a1-c1-neurons-contribute-to-the-maintenance-of-upper-airway-muscle-tone-but-may-not-participate-in-nrem-sleep-related-depression-of-these-muscles
#18
Irma Rukhadze, Nancy J Carballo, Sathyajit S Bandaru, Atul Malhotra, Patrick M Fuller, Victor B Fenik
Neural mechanisms of obstructive sleep apnea, a common sleep-related breathing disorder, are incompletely understood. Hypoglossal motoneurons, which provide tonic and inspiratory activation of genioglossus (GG) muscle (a major upper airway dilator), receive catecholaminergic input from medullary A1/C1 neurons. We aimed to determine the contribution of A1/C1 neurons in control of GG muscle during sleep and wakefulness. To do so, we placed injections of a viral vector into DBH-cre mice to selectively express the hMD4i inhibitory chemoreceptors in A1/C1 neurons...
July 12, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28710453/intrinsic-dynamics-study-identifies-two-amino-acids-of-timp-1-critical-for-its-lrp-1-mediated-endocytosis-in-neurons
#19
Laurie Verzeaux, Nicolas Belloy, Jessica Thevenard-Devy, Jérôme Devy, Géraldine Ferracci, Laurent Martiny, Stéphane Dedieu, Manuel Dauchez, Hervé Emonard, Nicolas Etique, Emmanuelle Devarenne-Charpentier
The tissue inhibitor of metalloproteinases-1 (TIMP-1) exerts inhibitory activity against matrix metalloproteinases and cytokine-like effects. We previously showed that TIMP-1 reduces neurite outgrowth in mouse cortical neurons and that this cytokine-like effect depends on TIMP-1 endocytosis mediated by the low-density lipoprotein receptor-related protein-1 (LRP-1). To gain insight into the interaction between TIMP-1 and LRP-1, we considered conformational changes that occur when a ligand binds to its receptor...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710408/non-ketogenic-combination-of-nutritional-strategies-provides-robust-protection-against-seizures
#20
Glenn Dallérac, Julien Moulard, Jean-François Benoist, Stefan Rouach, Stéphane Auvin, Angèle Guilbot, Loïc Lenoir, Nathalie Rouach
Epilepsy is a neurological condition that affects 1% of the world population. Conventional treatments of epilepsy use drugs targeting neuronal excitability, inhibitory or excitatory transmission. Yet, one third of patients presents an intractable form of epilepsy and fails to respond to pharmacological anti-epileptic strategies. The ketogenic diet is a well-established non-pharmacological treatment that has been proven to be effective in reducing seizure frequency in the pharmaco-resistant patients. This dietary solution is however extremely restrictive and can be associated with complications caused by the high [fat]:[carbohydrate + protein] ratio...
July 14, 2017: Scientific Reports
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