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Hyun Geun Shim, Dong Cheol Jang, Jaegeon Lee, Geehoon Chung, Sukchan Lee, Yong Gyu Kim, Da Eun Jeon, Sang Jeong Kim
Long-term depression (LTD) at the parallel fiber (PF)-to-cerebellar Purkinje cell (PC) synapse is implicated in the output of PCs, the sole output of the cerebellar cortex. In addition to synaptic plasticity, intrinsic excitability is also one of the components that determines PC output. Although long-term potentiation of intrinsic excitability (LTP-IE) has been suggested, it has yet to be investigated how PF-PC LTD modifies intrinsic excitability of PCs. Here, we show that pairing of the PF and climbing fiber (CF) for PF-PC LTD induction evokes LTD-IE in cerebellar PCs from male C57BL/6 mice...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Eriola Hoxha, Filippo Tempia, Pellegrino Lippiello, Maria Concetta Miniaci
The parallel fiber-Purkinje cell (PF-PC) synapse represents the point of maximal signal divergence in the cerebellar cortex with an estimated number of about 60 billion synaptic contacts in the rat and 100,000 billions in humans. At the same time, the Purkinje cell dendritic tree is a site of remarkable convergence of more than 100,000 parallel fiber synapses. Parallel fiber activity generates fast postsynaptic currents via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and slower signals, mediated by mGlu1 receptors, resulting in Purkinje cell depolarization accompanied by sharp calcium elevation within dendritic regions...
2016: Frontiers in Synaptic Neuroscience
Xiaojie Liu, Yao Chen, Casey R Vickstrom, Yan Li, Andreu Viader, Benjamin F Cravatt, Qing-Song Liu
The endocannabinoid 2-arachidonoylglycerol (2-AG) mediates retrograde synaptic depression including depolarization-induced suppression of excitation (DSE) and inhibition (DSI). 2-AG is degraded primarily by monoacylglycerol lipase (MAGL), which is expressed in neurons and astrocytes. Using knockout mice in which MAGL is deleted globally or selectively in neurons or astrocytes, we investigated the relative contribution of neuronal and astrocytic MAGL to the termination of DSE and DSI in Purkinje cells (PCs) in cerebellar slices...
October 24, 2016: Scientific Reports
Kazuhiko Yamaguchi, Shigeyoshi Itohara, Masao Ito
Long-term depression (LTD) of synaptic transmission from parallel fibers (PFs) to a Purkinje cell (PC) in the cerebellum has been considered to be a core mechanism of motor learning. Recently, however, discrepancies between LTD and motor learning have been reported in mice with a mutation that targeted the expression of PF-PC LTD by blocking AMPA-subtype glutamate receptor internalization regulated via the phosphorylation of AMPA receptors. In these mice, motor learning behavior was normal, but no PF-PC LTD was observed...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
Jonathan Elegheert, Wataru Kakegawa, Jordan E Clay, Natalie F Shanks, Ester Behiels, Keiko Matsuda, Kazuhisa Kohda, Eriko Miura, Maxim Rossmann, Nikolaos Mitakidis, Junko Motohashi, Veronica T Chang, Christian Siebold, Ingo H Greger, Terunaga Nakagawa, Michisuke Yuzaki, A Radu Aricescu
Ionotropic glutamate receptor (iGluR) family members are integrated into supramolecular complexes that modulate their location and function at excitatory synapses. However, a lack of structural information beyond isolated receptors or fragments thereof currently limits the mechanistic understanding of physiological iGluR signaling. Here, we report structural and functional analyses of the prototypical molecular bridge linking postsynaptic iGluR δ2 (GluD2) and presynaptic β-neurexin 1 (β-NRX1) via Cbln1, a C1q-like synaptic organizer...
July 15, 2016: Science
Zhen Yang, Fidel Santamaria
Coding in cerebellar Purkinje cells not only depends on synaptic plasticity but also on their intrinsic membrane excitability. We performed whole cell patch-clamp recordings of Purkinje cells in sagittal cerebellar slices in mice. We found that inducing long-term depression (LTD) in the parallel fiber to Purkinje cell synapses results in an increase in the gain of the firing rate response. This increase in excitability is accompanied by an increase in the input resistance and a decrease in the amplitude of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated voltage sag...
September 1, 2016: Journal of Neurophysiology
Yuan Wang, Jing Dong, Yi Wang, Wei Wei, Binbin Song, Zhongyan Shan, Weiping Teng, Jie Chen
Iodine is a significant micronutrient. Iodine deficiency (ID)-induced hypothyroxinemia and hypothyroidism during developmental period can cause cerebellar dysfunction. However, mechanisms are still unclear. Therefore, the present research aims to study effects of developmental hypothyroxinemia caused by mild ID and hypothyroidism caused by severe ID or methimazole (MMZ) on parallel fiber-Purkinje cell (PF-PC) synapses in filial cerebellum. Maternal hypothyroxinemia and hypothyroidism models were established in Wistar rats using ID diet and deionized water supplemented with different concentrations of potassium iodide or MMZ water...
October 2016: Biological Trace Element Research
K B Ramakrishnan, Kai Voges, Licia De Propris, Chris I De Zeeuw, Egidio D'Angelo
In the cerebellar network, a precise relationship between plasticity and neuronal discharge has been predicted. However, the potential generation of persistent changes in Purkinje cell (PC) spike discharge as a consequence of plasticity following natural stimulation patterns has not been clearly determined. Here, we show that facial tactile stimuli organized in theta-patterns can induce stereotyped N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA-A) receptor-dependent changes in PCs and molecular layer interneurons (MLIs) firing: invariably, all PCs showed a long-lasting increase (Spike-Related Potentiation or SR-P) and MLIs a long-lasting decrease (Spike-Related Suppression or SR-S) in baseline activity and spike response probability...
2016: Frontiers in Cellular Neuroscience
Andrew R Gallimore, A Radu Aricescu, Michisuke Yuzaki, Radu Calinescu
The expression of long-term depression (LTD) in cerebellar Purkinje cells results from the internalisation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) from the postsynaptic membrane. This process is regulated by a complex signalling pathway involving sustained protein kinase C (PKC) activation, inhibition of serine/threonine phosphatase, and an active protein tyrosine phosphatase, PTPMEG. In addition, two AMPAR-interacting proteins-glutamate receptor-interacting protein (GRIP) and protein interacting with C kinase 1 (PICK1)-regulate the availability of AMPARs for trafficking between the postsynaptic membrane and the endosome...
January 2016: PLoS Computational Biology
Jing Zhang, Jing Chen, Xiao-Li Tan, Ying-Ge Ren, Yong-Ping Du, Yue-Ping Zhang
OBJECTIVE: To investigate the protective effect of succinic acid (SA) on the cerebellar Purkinje cells (PCs) of neonatal rats with convulsion. METHODS: A total of 120 healthy neonatal Sprague-Dawley rats aged 7 days were randomly divided into a neonatal period group and a developmental period group. Each of the two groups were further divided into 6 sub-groups: normal control, convulsion model, low-dose phenobarbital (PB) (30 mg/kg), high-dose PB (120 mg/kg), low-dose SA (30 mg/kg), and high-dose SA (120 mg/kg)...
January 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Romain Ly, Guy Bouvier, German Szapiro, Haydn M Prosser, Andrew D Randall, Masanobu Kano, Kenji Sakimura, Philippe Isope, Boris Barbour, Anne Feltz
KEY POINTS: At the parallel fibre-Purkinje cell glutamatergic synapse, little or no Ca(2+) entry takes place through postsynaptic neurotransmitter receptors, although postsynaptic calcium increases are clearly involved in the synaptic plasticity. Postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid postsynaptic Ca(2+) signalling mechanism, making it essential to understand how they contribute to the synaptic signalling. Using a selective T-type calcium channel antagonist, we describe a T-type component of the EPSC that is activated by the AMPA receptor-mediated depolarization of the spine and thus will contribute to the local calcium dynamics...
February 15, 2016: Journal of Physiology
Hester R Trompetter, Ernst T Bohlmeijer, Jean-Paul Fox, Karlein M G Schreurs
The underlying mechanisms of the effectiveness of cognitive behavioural interventions for chronic pain need further clarification. The role of, and associations between, pain-related psychological flexibility (PF) and pain catastrophizing (PC) were examined during a randomized controlled trial on internet-based Acceptance & Commitment Therapy (ACT) for chronic pain. We assessed (1) the unique and combined indirect effects of PF and PC on outcomes, and (2) the causality of relations between PF, PC and the primary outcome pain interference in daily life (MPI) during ACT...
November 2015: Behaviour Research and Therapy
J Mans, T Y Murray, S Nadan, R Netshikweta, N A Page, M B Taylor
From 2009 to 2013 the diversity of noroviruses (NoVs) in children (⩽5 years) hospitalized with gastroenteritis in South Africa was investigated. NoVs were genotyped based on nucleotide sequence analyses of partial RNA-dependent RNA polymerase (RdRp) and capsid genes. Seventeen RdRp genotypes (GI.P2, GI.P3, GI.P6, GI.P7, GI.P not assigned (NA), GI.Pb, GI.Pf, GII.P2, GII.P4, GII.P7, GII.P13, GII.P16, GII.P21, GII.Pc, GII.Pe, GII.Pg, GII.PNA) and 20 capsid genotypes (GI.1, GI.2, GI.3, GI.5, GI.6, GI.7, GI.NA, GII...
April 2016: Epidemiology and Infection
Karen Siu-Lan Cheung, Bobo Hi-Po Lau
OBJECTIVES: This study applied a multidimensional model on a continuum to examine successful aging (SA) and investigated whether SA is associated with biomedical and psychosocial-demographic factors among Hong Kong Chinese near-centenarians and centenarians. METHOD: A cross-sectional data analysis was performed on a geographically representative sample of 120 near-centenarians and centenarians with an age range of 95-108 years. We developed an integrated and cumulative Successful Aging Index (SAI) based on participants' performance in four dimensions: (1) physical and functional health (PF), (2) psychological well-being and cognition (PC), (3) social engagement and family support (SF), (4) economic resources and financial security (EF)...
December 2016: Aging & Mental Health
Valentina Vanni, Francesca Puglisi, Paola Bonsi, Giulia Ponterio, Marta Maltese, Antonio Pisani, Georgia Mandolesi
Early-onset torsion dystonia (DYT1) is an autosomal-dominant movement disorder characterized by sustained muscle contractions and abnormal posturing. It is caused by a three base-pair deletion (ΔGAG) in the gene encoding the AAA(+) protein torsinA, which gives rise to a loss of function mutation responsible of neuronal functional abnormalities. Symptoms typically appear during childhood, suggesting the presence of an early critical period of sensorimotor circuit susceptibility to torsinA dysfunction. Here, we identified in two different DYT1 mouse strains, heterozygous torsinA knockout mice (Tor1a+/-) and human ΔGAG mutant torsinA transgenic mice (hMT), the anatomical abnormalities in the cerebellum, during a critical age for synaptogenesis (postnatal day 14, P14)...
September 2015: Experimental Neurology
Akira Iizuka, Yasunori Matsuzaki, Ayumu Konno, Hirokazu Hirai
Retinoid-related orphan receptor α (RORα) is a critical master transcription factor that governs postnatal cerebellar development. An RORα-deficient cerebellum has a persistent external granular layer (EGL), rudimentary Purkinje cell (PC) dendrites, grossly reduced numbers of immature parallel fiber (PF)-PC synapses, and multiple climbing fibers (CF) innervating PCs in mice after 3 weeks of age when these features have disappeared in wild-type mice. Functionally, metabotropic glutamate receptor (mGluR)-mediated signaling in PCs is completely abrogated...
July 2016: Brain Structure & Function
Yan-Hua Bing, Mao-Cheng Wu, Chun-Ping Chu, De-Lai Qiu
Cerebellar long-term synaptic plasticity has been proposed to provide a cellular mechanism for motor learning. Numerous studies have demonstrated the induction and mechanisms of synaptic plasticity at parallel fiber-Purkinje cell (PF-PC), parallel fiber-molecular layer interneurons (PF-MLI) and mossy fiber-granule cell (MF-GC) synapses, but no study has investigated sensory stimulation-evoked synaptic plasticity at MLI-PC synapses in the cerebellar cortex of living animals. We studied the expression and mechanism of MLI-PC GABAergic synaptic plasticity induced by a train of facial stimulation in urethane-anesthetized mice by cell-attached recordings and pharmacological methods...
2015: Frontiers in Cellular Neuroscience
Wei Teng, Changill Ban, Jong Hoon Hahn
This paper describes a new and facile approach for the formation of pore-spanning bilayer lipid membranes (BLMs) within a poly(dimethylsiloxane) (PDMS) microfluidic device. Commercially, readily available polycarbonate (PC) membranes are employed for the support of BLMs. PC sheets with 5 μm, 2 μm, and 0.4 μm pore diameters, respectively, are thermally bonded into a multilayer-stack, reducing the pore density of 0.4 μm-pore PC by a factor of 200. The BLMs on this support are considerably stable (a mean lifetime: 17 h)...
March 2015: Biomicrofluidics
Lowell M Smoger, Clare K Fitzpatrick, Chadd W Clary, Adam J Cyr, Lorin P Maletsky, Paul J Rullkoetter, Peter J Laz
The mechanics of the knee are complex and dependent on the shape of the articular surfaces and their relative alignment. Insight into how anatomy relates to kinematics can establish biomechanical norms, support the diagnosis and treatment of various pathologies (e.g., patellar maltracking) and inform implant design. Prior studies have used correlations to identify anatomical measures related to specific motions. The objective of this study was to describe relationships between knee anatomy and tibiofemoral (TF) and patellofemoral (PF) kinematics using a statistical shape and function modeling approach...
November 2015: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Céline Bidoret, Guy Bouvier, Annick Ayon, Germán Szapiro, Mariano Casado
N-methyl-D-aspartate receptors (NMDARs) in cerebellar molecular layer interneurons (MLIs) are expressed and activated in unusual ways: at parallel fibre (PF) synapses they are only recruited by repetitive stimuli, suggesting an extrasynaptic location, whereas their activation by climbing fibre is purely mediated by spillover. NMDARs are thought to play an important role in plasticity at different levels of the cerebellar circuitry. Evaluation of the location, functional properties and physiological roles of NMDARs will be facilitated by knowledge of the NMDAR isoforms recruited...
2015: Frontiers in Synaptic Neuroscience
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