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1.
Modification of ligand-gated receptor function at the postsynaptic domain is one of the most important mechanisms by which
the efficacy of synaptic transmission in the nervous system is regulated. Traditionally, these types of modifications have
been thought to be achieved mainly by altering the channel-gating properties or conductance of the receptors. However, recent
evidence suggests that AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxayolepropionic acid)-type ligand-gated glutamate receptors are continuously recycling between
the plasma membrane and the intracellular compartments via vesicle-mediated plasma membrane insertion and clathrin-dependent
endocytosis. Regulation of either receptor insertion or endocytosis results in a rapid change in the number of these receptors
expressed on the plasma membrane surface and in the receptor-mediated responses, thereby playing an important role in mediating
certain forms of synaptic plasticity. Thus, controlling the number of postsynaptic receptors by regulating the intracellular
trafficking and plasma membrane expression of the postsynaptic receptors may be a common and important mechanism of synaptic
plasticity in the mammalian central nervous system. 相似文献
2.
Massicotte G 《Cellular and molecular life sciences : CMLS》2000,57(11):1542-1550
Long-term potentiation (LTP) and long-term depression (LTD) are two electrophysiological models that have been studied extensively in recent years as they may represent basic mechanisms in many neuronal networks to store certain types of information. In several brain regions, it has been shown that these two forms of synaptic plasticity require sufficient dendritic depolarization, with the amplitude of the calcium signal being crucial for the generation of either LTP or LTD. The rise in calcium concentration mediated by the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors has been proposed to stimulate various calcium-dependent enzymatic processes that could convert the induction signal into long-lasting changes in synaptic structure; protein kinases and phosphatases have so far been considered predominantly with regard to LTP and LTD formation. According to several lines of experimental evidence, changes in synaptic function observed with LTP and LTD are thought to be the result of modifications of postsynaptic currents mediated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptors. Moreover, it has become apparent recently that activation of the calcium-dependent enzyme phospholipase A2 (PLA2) could be part of the molecular mechanisms involved in alterations of AMPA receptor properties during long-term changes in synaptic operation. In the present review, we will first describe the results that indicate a critical role of the phospholipases in regulating synaptic function. Next, sections will be devoted to the effects of PLA2 and phospholipids on the binding properties of glutamate receptors, and a revised biochemical model will be presented as an attempt to integrate the PLA2 enzyme into the mechanisms ( in particular kinases and phosphatases) that participate in adaptive neural plasticity. Finally, we will review data relevant to the issue of selective changes in AMPA binding after environmental enrichment and LTP. 相似文献
3.
Silvia Bassani Alessandra Folci Jonathan Zapata Maria Passafaro 《Cellular and molecular life sciences : CMLS》2013,70(23):4411-4430
Glutamate ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate most fast excitatory synaptic transmission in the central nervous system. The content and composition of AMPARs in postsynaptic membranes (which determine synaptic strength) are dependent on the regulated trafficking of AMPAR subunits in and out of the membranes. AMPAR trafficking is a key mechanism that drives nascent synapse development, and is the main determinant of both Hebbian and homeostatic plasticity in mature synapses. Hebbian plasticity seems to be the biological substrate of at least some forms of learning and memory; while homeostatic plasticity (also known as synaptic scaling) keeps neuronal circuits stable by maintaining changes within a physiological range. In this review, we examine recent findings that provide further understanding of the role of AMPAR trafficking in synapse maturation, Hebbian plasticity, and homeostatic plasticity. 相似文献
4.
Glutamate, by activation of metabotropic receptors (mGluRs), can lead to a reduction of synaptic efficacy at many synapses.
These forms of synaptic plasticity are referred to as long-term depression (mGluR-LTD). We will distinguish between mGluR-LTD
induced by pre- or postsynaptic receptors and mGluR-LTD induced by the locus of the expression mechanism of the synaptic depression.
We will also review recent evidence that mGluR-mediated responses themselves are subject to depression, which may constitute
a form of metaplasticity.
Received 13 May 2008; received after revision 07 July 2008; accepted 11 July 2008 相似文献
5.
M. B. Moser 《Cellular and molecular life sciences : CMLS》1999,55(4):593-600
Although information may be stored in the brain as changes in the strength of existing synapses, formation of new synapses
has long been thought of as an additional substrate for memory storage. The identification of subcellular structural changes
following learning in mammals poses a serious ‘needle-in-the-haystack’ problem. In most attempts to demonstrate structural
plasticity during learning, animals have been exposed for prolonged periods to complex environments, where they are confronted
with a variety of sensory, motor and spatial challenges throughout the exposure period. These environments are thought to
promote several forms of learning. Repeated exposure to such environments has been shown to increase the density of spines
and dendritic complexity in relevant brain structures. The number of neurons has also been reported to increase in some areas.
It is not clear, however, whether the new synapses emerging from these forms of plasticity mediate specific information storage,
or whether they reflect a more general sophistication of the excited parts of the network. 相似文献
6.
Franciosi S 《Cellular and molecular life sciences : CMLS》2001,58(7):921-930
α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors are one type of ionotropic glutamate receptor involved
in rapid excitatory synaptic transmission. AMPA receptors have been increasingly implicated in long-term potentiation, and
recent evidence suggests that they may play a role in disorders affecting the nervous system. The finding that early in postnatal
development AMPA receptors are not expressed has lately been the focus of much attention. Resolving the factors involved in
AMPA receptor expression suggests that their induction is a developmentally regulated process with the possibility that alterations
in receptor expression may be correlated with pathology in neurological disorders. This paper provides an overview of factors
involved in AMPA receptor induction as well as of their role in plasticity and neuronal pathologies.
Received 5 December 2000; received after revision 12 January 2001; accepted 2 February 2001 相似文献
7.
Tissue-specific modulation of rat glucocorticoid receptor binding activity by melatonin 总被引:1,自引:0,他引:1
P. St. Persengiev DVM Ph.D. I. I. Kondova 《Cellular and molecular life sciences : CMLS》1993,49(4):332-334
The effect of melatonin and 2-Iodomelatonin on nuclear and cytosolic glucocorticoid receptors in the brain, pituitary, thymus and liver has been examined. The results indicate that both melatonin and 2-Iodomelatonin administration is associated with marked changes in the density and the affinity of cytosolic and nuclear forms of glucocorticoid receptors. These observations are discussed in the context of a possible involvement of pineal melatonin in the mechanisms regulating the behaviour and metabolism of steroid receptors. 相似文献
8.
Molecular and functional heterogeneity of GABAergic synapses 总被引:1,自引:1,他引:0
Fritschy JM Panzanelli P Tyagarajan SK 《Cellular and molecular life sciences : CMLS》2012,69(15):2485-2499
Knowledge of the functional organization of the GABAergic system, the main inhibitory neurotransmitter system, in the CNS has increased remarkably in recent years. In particular, substantial progress has been made in elucidating the molecular mechanisms underlying the formation and plasticity of GABAergic synapses. Evidence available ascribes a key role to the cytoplasmic protein gephyrin to form a postsynaptic scaffold anchoring GABA(A) receptors along with other transmembrane proteins and signaling molecules in the postsynaptic density. However, the mechanisms of gephyrin scaffolding remain elusive, notably because gephyrin can auto-aggregate spontaneously and lacks PDZ protein interaction domains found in a majority of scaffolding proteins. In addition, the structural diversity of GABA(A) receptors, which are pentameric channels encoded by a large family of subunits, has been largely overlooked in these studies. Finally, the role of the dystrophin-glycoprotein complex, present in a subset of GABAergic synapses in cortical structures, remains ill-defined. In this review, we discuss recent results derived mainly from the analysis of mutant mice lacking a specific GABA(A) receptor subtype or a core protein of the GABAergic postsynaptic density (neuroligin-2, collybistin), highlighting the molecular diversity of GABAergic synapses and its relevance for brain plasticity and function. In addition, we discuss the contribution of the dystrophin-glycoprotein complex to the molecular and functional heterogeneity of GABAergic synapses. 相似文献
9.
Rafael Andrés Posada-Duque Omar Ramirez Steffen Härtel Nibaldo C. Inestrosa Felipe Bodaleo Christian González-Billault Alfredo Kirkwood Gloria Patricia Cardona-Gómez 《Cellular and molecular life sciences : CMLS》2017,74(1):153-172
CDK5 is a serine/threonine kinase that is involved in the normal function of the adult brain and plays a role in neurotransmission and synaptic plasticity. However, its over-regulation has been associated with Tau hyperphosphorylation and cognitive deficits. Our previous studies have demonstrated that CDK5 targeting using shRNA-miR provides neuroprotection and prevents cognitive deficits. Dendritic spine morphogenesis and forms of long-term synaptic plasticity—such as long-term potentiation (LTP)—have been proposed as essential processes of neuroplasticity. However, whether CDK5 participates in these processes remains controversial and depends on the experimental model. Using wild-type mice that received injections of CDK5 shRNA-miR in CA1 showed an increased LTP and recovered the PPF in deficient LTP of APPswe/PS1Δ9 transgenic mice. On mature hippocampal neurons CDK5, shRNA-miR for 12 days induced increased dendritic protrusion morphogenesis, which was dependent on Rac activity. In addition, silencing of CDK5 increased BDNF expression, temporarily increased phosphorylation of CaMKII, ERK, and CREB; and facilitated calcium signaling in neurites. Together, our data suggest that CDK5 downregulation induces synaptic plasticity in mature neurons involving Ca2+ signaling and BDNF/CREB activation. 相似文献
10.
MAGUKs in synapse assembly and function: an emerging view 总被引:4,自引:0,他引:4
Montgomery JM Zamorano PL Garner CC 《Cellular and molecular life sciences : CMLS》2004,61(7-8):911-929
11.
Parameshwaran K Buabeid MA Karuppagounder SS Uthayathas S Thiruchelvam K Shonesy B Dityatev A Escobar MC Dhanasekaran M Suppiramaniam V 《Cellular and molecular life sciences : CMLS》2012,69(5):829-841
In the developing brain, nicotinic acetylcholine receptors (nAChRs) are involved in cell survival, targeting, formation of
neural and sensory circuits, and development and maturation of other neurotransmitter systems. This regulatory role is disrupted
when the developing brain is exposed to nicotine, which occurs with tobacco use during pregnancy. Prenatal nicotine exposure
has been shown to be a strong risk factor for memory deficits and other behavioral aberrations in the offspring. The molecular
mechanisms underlying these neurobehavioral outcomes are not clearly elucidated. We used a rodent model to assess behavioral,
neurophysiological, and neurochemical consequences of prenatal nicotine exposure in rat offspring with specific emphasis on
the hippocampal glutamatergic system. Pregnant dams were infused with nicotine (6 mg/kg/day) subcutaneously from the third
day of pregnancy until birth. Results indicate that prenatal nicotine exposure leads to increased anxiety and depressive-like
effects and impaired spatial memory. Synaptic plasticity in the form of long-term potentiation (LTP), basal synaptic transmission,
and AMPA receptor-mediated synaptic currents were reduced. The deficit in synaptic plasticity was paralleled by declines in
protein levels of vesicular glutamate transporter 1 (VGLUT1), synaptophysin, AMPA receptor subunit GluR1, phospho(Ser845)
GluR1, and postsynaptic density 95 (PSD-95). These results suggest that prenatal nicotine exposure by maternal smoking could
result in alterations in the glutamatergic system in the hippocampus contributing to the abnormal neurobehavioral outcomes. 相似文献
12.
A set of fundamental issues in neuroethology concerns the neural mechanisms underlying behavior and behavioral plasticity. We have recently analyzed these issues by combining a simple systems approach in the marine mollusc Aplysia with a developmental analysis aimed at examining the emergence and maturation of different forms of behavior and learning. We have focussed on two kinds of questions: 1) How are specific neural circuits developmentally assembled to mediate different types of behaviors? and 2) how is plasticity integrated with these circuits to give rise to different forms of learning? From our analysis of the development of learning and memory in Aplysia, several themes have emerged: 1) Different forms of learning emerge according to different developmental timetables. 2) Cellular analogs of learning have the same developmental timetables as their respective forms of behavioral learning. 3) An analysis of non-decremented responses prior to the emergence of sensitization reveals a novel inhibitory process on both behavioral and cellular levels. 4) Sensitization emerges simultaneously in diverse response systems, suggesting an underlying general process. 5) A widespread proliferation of central neurons occurs in the same developmental stage as the emergence of sensitization, raising the possibility that some aspect of the trigger for neuronal proliferation may also contribute to the expression of sensitization. 相似文献
13.
Stenberg D 《Cellular and molecular life sciences : CMLS》2007,64(10):1187-1204
Sleep is regulated by homeostatic and circadian factors, and the regulation of sleep of mammals shares many molecular properties
with the rest state of submammalian species. Several brain structures take part in waking: the basal forebrain, posterior
and lateral hypothalamus, and nuclei in the tegmentum and pons. Active sleep mechanisms are located to the preoptic/anterior
hypothalamic area. In addition to acetylcholine and monoamines, glutamate and hypocretin/orexin are important waking factors.
Gamma-aminobutyric acid and several peptide factors, including cytokines, growth hormone-releasing hormone and prolactin,
are related to sleep promotion. Adenosine is an important homeostatic sleep factor acting in basal forebrain and preoptic
areas through A1 and A2A receptors. Prolonged waking activates inducible nitric oxide synthase in the basal forebrain, which
through energy depletion causes adenosine release and recovery sleep. Numerous genes have been found differentially displayed
in waking compared with sleep, and they relate to neural transmission, synaptic plasticity, energy metabolism and stress protection.
The genetic background of a few sleep disorders has been solved. 相似文献
14.
Mocchetti I 《Cellular and molecular life sciences : CMLS》2005,62(19-20):2283-2294
Gangliosides, a heterogeneous family of glycosphingolipids abundant in the brain, have been shown to affect neuronal plasticity during development, adulthood and aging. This review will examine old and recent evidence that exogenous gangliosides and in particular GM1, the prototype member of this family, exhibit multimodal neurotrophic effects. Since these compounds are a potential therapeutic tool for the treatment of various forms of acute or chronic neurodegenerative diseases, understanding the dynamic interplay of gangliosides and neuronal cells is essential in the effort to cure neurological disorders. Focus will be given to the novel and provocative hypothesis that gangliosides' neuroprotective properties may derive from their ability to mimic endogenous neurotrophic factors. 相似文献
15.
Brice Hoffmann Ahmad Elbahnsi Pierre Lehn Jean-Luc Décout Fabio Pietrucci Jean-Paul Mornon Isabelle Callebaut 《Cellular and molecular life sciences : CMLS》2018,75(20):3829-3855
Cryo-electron microscopy (cryo-EM) has recently provided invaluable experimental data about the full-length cystic fibrosis transmembrane conductance regulator (CFTR) 3D structure. However, this experimental information deals with inactive states of the channel, either in an apo, quiescent conformation, in which nucleotide-binding domains (NBDs) are widely separated or in an ATP-bound, yet closed conformation. Here, we show that 3D structure models of the open and closed forms of the channel, now further supported by metadynamics simulations and by comparison with the cryo-EM data, could be used to gain some insights into critical features of the conformational transition toward active CFTR forms. These critical elements lie within membrane-spanning domains but also within NBD1 and the N-terminal extension, in which conformational plasticity is predicted to occur to help the interaction with filamin, one of the CFTR cellular partners. 相似文献
16.
E. A. Marcus T. G. Nolen C. H. Rankin M. Stopfer T. J. Carew 《Cellular and molecular life sciences : CMLS》1988,44(5):415-423
Summary A set of fundamental issues in neuroethology concerns the neural mechanisms underlying behavior and behavioral plasticity. We have recently analyzed these issues by combining a simple systems approach in the marine molluscAplysia with a developmental analysis aimed at examining the emergence and maturation of different forms of behavior and learning. We have focussed on two kinds of questions: 1) How are specific neural circuits developmentally assembled to mediate different types of behaviors? and 2) how is plasticity integrated with these circuits to give rise to different forms of learning? From our analysis of the development of learning and memory inAplysia, several themes have emerged: 1) Different forms of learning emerge according to different developmental timetables. 2) Cellular analogs of learning have the same developmental timetables as their respective forms of behavioral learing. 3) An analysis of non-decremented responses prior to the emergence of sensitization reveals a novel inhibitory process on both behavioral and cellular levels. 4) Sensitization emerges simultaneously in diverse response systems, suggesting an underlying general process. 5) A widespread proliferation of central neurons occurs in the same developmental stage as the emergence of sensitization, raising the possibility that some aspect of the trigger for neuronal proliferation may also contribute to the expression of sensitization. 相似文献
17.
18.
Gonadotropin or TSH treated newborn animals reacted to TSH treatment in their adult age in a lesser degree than control ones. This suggests the plasticity of hormone receptors and the possibility of their deformation in neonatal age. 相似文献
19.
Summary Gonadotropin or TSH treated newborn animals reacted to TSH treatment in their adult age in a lesser degree than control ones. This suggests the plasticity of hormone receptors and the possibility of their deformation in neonatal age. 相似文献
20.
Zeilhofer HU 《Cellular and molecular life sciences : CMLS》2005,62(18):2027-2035
Alterations in synaptic transmission within the spinal cord dorsal horn play a key role in the development of pathological pain. While N-methyl-D-aspartate (NMDA) receptors and activity-dependent synaptic plasticity have been the focus of research for many years, recent evidence attributes very specific functions to inhibitory glycinergic and γ-aminobutyric acid (GABA)-ergic neurotransmission in the generation of inflammatory and neuropathic pain. The central component of inflammatory pain originates from a disinhibition of dorsal horn neurons, which are relieved from glycinergic neurotransmission by the inflammatory mediator prostaglandin E2 (PGE2). PGE2 activates prostaglandin E receptors of the EP2 subtype and leads to a protein kinase A-dependent phosphorylation and inhibition of glycine receptors containing the α3 subunit (GlyRα3). This GlyRα3 is distinctly expressed in the superficial dorsal horn, where nociceptive afferents terminate. Other but probably very similar disinhibitory mechanisms may well contribute to abnormal pain occurring after peripheral nerve injury.Received 11 March 2005; received after revision 1 April 2005; accepted 19 April 2005 相似文献