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https://www.readbyqxmd.com/read/29034487/the-role-of-spontaneous-neurotransmission-in-synapse-and-circuit-development
#1
REVIEW
Laura C Andreae, Juan Burrone
In the past, the spontaneous release of neurotransmitter from presynaptic terminals has been thought of as a side effect of evoked release, with little functional significance. As our understanding of the process of spontaneous release has increased over time, this notion has gradually changed. In this review, we focus on the importance of this form of release during neuronal development, a time of extreme levels of plasticity that includes the growth of dendrites and axons as well as the formation of new synaptic contacts...
October 16, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29031852/inhibition-of-cdk5-rejuvenates-inhibitory-circuits-and-restores-experience-dependent-plasticity-in-adult-visual-cortex
#2
Yue Li, Laijian Wang, Xinxin Zhang, Mengyao Huang, Sitong Li, Xinxing Wang, Lin Chen, Bin Jiang, Yupeng Yang
Cyclin-dependent kinase 5 (Cdk5) acts as an essential modulator for neural development and neurological disorders. Here we show that Cdk5 plays a pivotal role in modulating GABAergic signaling and the maturation of visual system. In adult mouse primary visual cortex, Cdk5 formed complex with the GABA synthetic enzyme glutamate decarboxylase GAD67, but not with GAD65. In addition to enhancement in the surface level of NR2B-containing NMDA receptors, inhibition of Cdk5 reduced the protein levels of GADs and Otx2, while leaving intact the expression of vesicular GABA transporter and subunits of GABAA or AMPA receptors...
October 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29030733/high-yield-preparation-of-functionally-active-catalytic-translocation-domain-module-of-botulinum-neurotoxin-type-a-that-exhibits-uniquely-different-enzyme-kinetics
#3
Harkiranpreet Kaur Dhaliwal, Nagarajan Thiruvanakarasu, Raj Kumar, Kruti Patel, Ghuncha Ambrin, Shouwei Cai, Bal Ram Singh
Botulinum neurotoxins (BoNTs) are the most toxic proteins known to cause flaccid muscle paralysis as a result of inhibition of neurotransmitter release from peripheral cholinergic synapses. BoNT type A (BoNT/A) is a 150 kDa protein consisting of two major subunits: light chain (LC) and heavy chain (HC). The LC is required for the catalytic activity of neurotoxin, whereas the C and N terminal domains of the HC are required for cell binding, and translocation of LC across the endosome membranes, respectively...
October 13, 2017: Protein Journal
https://www.readbyqxmd.com/read/29029315/7-8-dihydroxyflavone-rescues-lead-induced-impairment-of-vesicular-release-a-novel-therapeutic-approach-for-lead-intoxicated-children
#4
Xiao-Lei Zhang, Jennifer L McGlothan, Omid Miry, Kirstie H Stansfield, Meredith K Loth, Patric K Stanton, Tomás R Guilarte
Childhood lead (Pb2+) intoxication is a public health problem of global proportion. Lead exposure during development produces multiple effects on the central nervous system including impaired synapse formation, altered synaptic plasticity, and learning deficits.In primary hippocampal neurons in culture and hippocampal slices, Pb2+ exposure inhibits vesicular release and reduces the number of fast-releasing sites, an effect associated with Pb2+ inhibition of NMDA receptor-mediated trans-synaptic Brain-Derived Neurotrophic Factor (BDNF) signaling...
October 4, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29028947/dlx1-and-dlx2-promote-interneuron-gaba-synthesis-synaptogenesis-and-dendritogenesis
#5
Ramon Pla, Amelia Stanco, MacKenzie A Howard, Anna N Rubin, Daniel Vogt, Niall Mortimer, Inma Cobos, Gregory Brian Potter, Susan Lindtner, James D Price, Alex S Nord, Axel Visel, Christoph E Schreiner, Scott C Baraban, David H Rowitch, John L R Rubenstein
The postnatal functions of the Dlx1&2 transcription factors in cortical interneurons (CINs) are unknown. Here, using conditional Dlx1, Dlx2, and Dlx1&2 knockouts (CKOs), we defined their roles in specific CINs. The CKOs had dendritic, synaptic, and survival defects, affecting even PV+ CINs. We provide evidence that DLX2 directly drives Gad1, Gad2, and Vgat expression, and show that mutants had reduced mIPSC amplitude. In addition, the mutants formed fewer GABAergic synapses on excitatory neurons and had reduced mIPSC frequency...
September 28, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29026183/developmental-emergence-of-sparse-coding-a-dynamic-systems-approach
#6
Vahid Rahmati, Knut Kirmse, Knut Holthoff, Lars Schwabe, Stefan J Kiebel
During neocortical development, network activity undergoes a dramatic transition from largely synchronized, so-called cluster activity, to a relatively sparse pattern around the time of eye-opening in rodents. Biophysical mechanisms underlying this sparsification phenomenon remain poorly understood. Here, we present a dynamic systems modeling study of a developing neural network that provides the first mechanistic insights into sparsification. We find that the rest state of immature networks is strongly affected by the dynamics of a transient, unstable state hidden in their firing activities, allowing these networks to either be silent or generate large cluster activity...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024789/in-vitro-pharmacological-characterization-of-the-bispyridinium-non-oxime-compound-mb327-and-its-2-and-3-regioisomers
#7
K V Niessen, T Seeger, S Rappenglück, T Wein, G Höfner, K T Wanner, H Thiermann, F Worek
The primary toxic mechanism of organophosphorus compounds, i.e. nerve agents or pesticides, is based on the irreversible inhibition of acetylcholinesterase. In consequence of the impaired hydrolysis, the neurotransmitter acetylcholine accumulates in cholinergic synapses and disturbs functional activity of nicotinic and muscarinic acetylcholine receptors by overstimulation and subsequent desensitization. The resulting cholinergic syndrome will become acute life-threatening, if not treated adequately. The current standard treatment, consisting of administration of a competitive mAChR antagonist (e...
October 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29024665/astrocyte-secreted-glypican-4-regulates-release-of-neuronal-pentraxin-1-from-axons-to-induce-functional-synapse-formation
#8
Isabella Farhy-Tselnicker, Adriana C M van Casteren, Aletheia Lee, Veronica T Chang, A Radu Aricescu, Nicola J Allen
The generation of precise synaptic connections between developing neurons is critical to the formation of functional neural circuits. Astrocyte-secreted glypican 4 induces formation of active excitatory synapses by recruiting AMPA glutamate receptors to the postsynaptic cell surface. We now identify the molecular mechanism of how glypican 4 exerts its effect. Glypican 4 induces release of the AMPA receptor clustering factor neuronal pentraxin 1 from presynaptic terminals by signaling through presynaptic protein tyrosine phosphatase receptor δ...
October 11, 2017: Neuron
https://www.readbyqxmd.com/read/29020745/transcriptional-mapping-of-the-primary-somatosensory-cortex-upon-sensory-deprivation
#9
Koen Kole, Yutaro Komuro, Jan Provaznik, Jelena Pistolic, Vladimir Benes, Paul Tiesinga, Tansu Celikel
Experience-dependent plasticity (EDP) is essential for anatomical and functional maturation of sensory circuits during development. Although the principal synaptic and circuit mechanisms of EDP are increasingly well studied experimentally and computationally, its molecular mechanisms remain largely elusive. EDP can be readily studied in the rodent barrel cortex, where each "barrel column" preferentially represents deflections of its own principal whisker. Depriving select whiskers while sparing their neighbours introduces competition between barrel columns, ultimately leading to weakening of intracortical, translaminar (i...
October 1, 2017: GigaScience
https://www.readbyqxmd.com/read/29020622/homeostatic-presynaptic-plasticity-is-specifically-regulated-by-p-q-type-ca-2-channels-at-mammalian-hippocampal-synapses
#10
Alexander F Jeans, Fran C van Heusden, Bashayer Al-Mubarak, Zahid Padamsey, Nigel J Emptage
Voltage-dependent Ca(2+) channels (VGCC) represent the principal source of Ca(2+) ions driving evoked neurotransmitter release at presynaptic boutons. In mammals, presynaptic Ca(2+) influx is mediated mainly via P/Q-type and N-type VGCC, which differ in their properties. Changes in their relative contributions tune neurotransmission both during development and in Hebbian plasticity. However, whether this represents a functional motif also present in other forms of activity-dependent regulation is unknown. Here, we study the role of VGCC in homeostatic plasticity (HSP) in mammalian hippocampal neurons using optical techniques...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/29018766/acute-angle-closure-following-periorbital-botulinum-toxin-injection-in-a-patient-with-retinitis-pigmentosa
#11
Jen-Chia Tsai
A 50-year-old female presented with bilateral retinitis pigmentosa (RP) and acute angle closure (AAC) with fixed mid-dilated pupil and high intraocular pressure (IOP) in the left eye following left side periorbital botulinum toxin A injection for blepharospasm. Glaucomatous optic neuropathy and retinal nerve fiber layer defect were observed in the affected eye using optical coherence tomography although the IOP was maintained at <21 mmHg after the treatment. Botulinum toxin acts at the cholinergic synapse and inhibits acetylcholine release; hence, it can cause transient mydriasis and may lead to AAC in high-risk populations such as patients with RP...
April 2017: Taiwan Journal of Ophthalmology
https://www.readbyqxmd.com/read/28990294/genetic-and-molecular-risk-factors-within-the-newly-identified-primate-specific-exon-of-the-sap97-dlg1-gene-in-the-3q29-schizophrenia-associated-locus
#12
Akihito Uezato, Naoki Yamamoto, Daisuke Jitoku, Emiko Haramo, Eri Hiraaki, Yoshimi Iwayama, Tomoko Toyota, Masakazu Umino, Asami Umino, Yasuhide Iwata, Katsuaki Suzuki, Mitsuru Kikuchi, Tasuku Hashimoto, Nobuhisa Kanahara, Akeo Kurumaji, Takeo Yoshikawa, Toru Nishikawa
The synapse-associated protein 97/discs, large homolog 1 of Drosophila (DLG1) gene encodes synaptic scaffold PDZ proteins interacting with ionotropic glutamate receptors including the N-methyl-D-aspartate type glutamate receptor (NMDAR) that is presumed to be hypoactive in brains of patients with schizophrenia. The DLG1 gene resides in the chromosomal position 3q29, the microdeletion of which confers a 40-fold increase in the risk for schizophrenia. In the present study, we performed genetic association analyses for DLG1 gene using a Japanese cohort with 1808 schizophrenia patients and 2170 controls...
October 9, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28982705/sk-channels-regulate-resting-properties-and-signaling-reliability-of-a-developing-fast-spiking-neuron
#13
Yihui Zhang, Hai Huang
Reliable and precise signal transmission is essential in circuits of the auditory brainstem in order to encode timing with submillisecond accuracy. Globular bushy cells reliably and faithfully transfer spike signals to the principal neurons of the medial nucleus of the trapezoid body (MNTB) through the giant glutamatergic synapse, the calyx of Held. Thus, the MNTB works as a relay nucleus that preserves the temporal pattern of firing at high frequency. Using whole-cell patch-clamp recordings, we observed a K(+) conductance mediated by small-conductance calcium-activated potassium (SK) channels in the MNTB neurons from rats of either sex...
October 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28982282/long-synfire-chains-emerge-by-spike-timing-dependent-plasticity-modulated-by-population-activity
#14
Felix Weissenberger, Florian Meier, Johannes Lengler, Hafsteinn Einarsson, Angelika Steger
Sequences of precisely timed neuronal activity are observed in many brain areas in various species. Synfire chains are a well-established model that can explain such sequences. However, it is unknown under which conditions synfire chains can develop in initially unstructured networks by self-organization. This work shows that with spike-timing dependent plasticity (STDP), modulated by global population activity, long synfire chains emerge in sparse random networks. The learning rule fosters neurons to participate multiple times in the chain or in multiple chains...
September 7, 2017: International Journal of Neural Systems
https://www.readbyqxmd.com/read/28981586/gabapentin-prevents-progressive-increases-in-excitatory-connectivity-and-epileptogenesis-following-neocortical-trauma
#15
D K Takahashi, Sha Jin, D A Prince
Neocortical injury initiates a cascade of events, some of which result in maladaptive epileptogenic reorganization of surviving neural circuits. Research focused on molecular and organizational changes that occur following trauma may reveal processes that underlie human post-traumatic epilepsy (PTE), a common and unfortunate consequence of traumatic brain injury. The latency between injury and development of PTE provides an opportunity for prophylactic intervention, once the key underlying mechanisms are understood...
June 26, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28979189/uncorrelated-neural-firing-in-mouse-visual-cortex-during-spontaneous-retinal-waves
#16
Matthew T Colonnese, Jing Shen, Yasunobu Murata
Synchronous firing among the elements of forming circuits is critical for stabilization of synapses. Understanding the nature of these local network interactions during development can inform models of circuit formation. Within cortex, spontaneous activity changes throughout development. Unlike the adult, early spontaneous activity occurs in discontinuous population bursts separated by long silent periods, suggesting a high degree of local synchrony. However, whether the micro-patterning of activity within early bursts is unique to this early age and specifically tuned for early development is poorly understood, particularly within the column...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28979185/the-membrane-glycoprotein-m6a-endocytic-recycling-pathway-involves-clathrin-mediated-endocytosis-and-affects-neuronal-synapses
#17
Micaela D Garcia, Karina Formoso, Gabriela I Aparicio, Alberto C C Frasch, Camila Scorticati
Single point mutations or variations in the expression of the gene encoding the neuronal glycoprotein M6a have been associated with psychiatric disorders such as Alzheimer's disease, depression and schizophrenia. In cultured neurons, M6a positively contributes to neurite extension, axon guidance, filopodia/spine outgrowth, and synapse formation. The endocytic processes of neuronal membrane proteins are linked to the differentiation, growth, signaling and plasticity of neurons. However, the roles of M6a and the precise mechanisms through which M6a internalizes and recycles back to the neuronal membrane are unknown...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28978806/dock8-enforces-immunological-tolerance-by-promoting-il-2-signaling-and-immune-synapse-formation-in-tregs
#18
Erin Janssen, Sudha Kumari, Mira Tohme, Sumana Ullas, Victor Barrera, Jeroen Mj Tas, Marcela Castillo-Rama, Roderick T Bronson, Shariq M Usmani, Darrell J Irvine, Thorsten R Mempel, Raif S Geha
Patients deficient in the guanine nucleotide exchange factor DOCK8 have decreased numbers and impaired in vitro function of Tregs and make autoantibodies, but they seldom develop autoimmunity. We show that, similarly, Dock8-/- mice have decreased numbers and impaired in vitro function of Tregs but do not develop autoimmunity. In contrast, mice with selective DOCK8 deficiency in Tregs develop lymphoproliferation, autoantibodies, and gastrointestinal inflammation, despite a normal percentage and in vitro function of Tregs, suggesting that deficient T effector cell function might protect DOCK8-deficient patients from autoimmunity...
October 5, 2017: JCI Insight
https://www.readbyqxmd.com/read/28978465/sarm1-deletion-but-not-wld-s-confers-lifelong-rescue-in-a-mouse-model-of-severe-axonopathy
#19
Jonathan Gilley, Richard R Ribchester, Michael P Coleman
Studies with the Wld(S) mutant mouse have shown that axon and synapse pathology in several models of neurodegenerative diseases are mechanistically related to injury-induced axon degeneration (Wallerian degeneration). Crucially, an absence of SARM1 delays Wallerian degeneration as robustly as Wld(S), but their relative capacities to confer long-term protection against related, non-injury axonopathy and/or synaptopathy have not been directly compared. While Sarm1 deletion or Wld(S) can rescue perinatal lethality and widespread Wallerian-like axonopathy in young NMNAT2-deficient mice, we report that an absence of SARM1 enables these mice to survive into old age with no overt phenotype, whereas those rescued by Wld(S) invariantly develop a progressive neuromuscular defect in their hindlimbs from around 3 months of age...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28973908/substance-p-induces-plasticity-and-synaptic-tagging-capture-in-rat-hippocampal-area-ca2
#20
Ananya Dasgupta, Nimmi Baby, Kumar Krishna, Muhammad Hakim, Yuk Peng Wong, Thomas Behnisch, Tuck Wah Soong, Sreedharan Sajikumar
The hippocampal area Cornu Ammonis (CA) CA2 is important for social interaction and is innervated by Substance P (SP)-expressing supramammillary (SuM) nucleus neurons. SP exerts neuromodulatory effects on pain processing and central synaptic transmission. Here we provide evidence that SP can induce a slowly developing NMDA receptor- and protein synthesis-dependent potentiation of synaptic transmission that can be induced not only at entorhinal cortical (EC)-CA2 synapses but also at long-term potentiation (LTP)-resistant Schaffer collateral (SC)-CA2 synapses...
September 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
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