scholarly journals N-cadherin mediates plasticity-induced long-term spine stabilization

2010 ◽  
Vol 189 (3) ◽  
pp. 589-600 ◽  
Author(s):  
Pablo Mendez ◽  
Mathias De Roo ◽  
Lorenzo Poglia ◽  
Paul Klauser ◽  
Dominique Muller
Keyword(s):  
Molecular Mechanisms ◽  
Stable State ◽  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Loss Of Function ◽  
Long Term Stability ◽  
Spine Stabilization ◽  
Term Potentiation ◽  
Dynamic Structures

Excitatory synapses on dendritic spines are dynamic structures whose stability can vary from hours to years. However, the molecular mechanisms regulating spine persistence remain essentially unknown. In this study, we combined repetitive imaging and a gain and loss of function approach to test the role of N-cadherin (NCad) on spine stability. Expression of mutant but not wild-type NCad promotes spine turnover and formation of immature spines and interferes with the stabilization of new spines. Similarly, the long-term stability of preexisting spines is reduced when mutant NCad is expressed but enhanced in spines expressing NCad-EGFP clusters. Activity and long-term potentiation (LTP) induction selectively promote formation of NCad clusters in stimulated spines. Although activity-mediated expression of NCad-EGFP switches synapses to a highly stable state, expression of mutant NCad or short hairpin RNA–mediated knockdown of NCad prevents LTP-induced long-term stabilization of synapses. These results identify NCad as a key molecular component regulating long-term synapse persistence.

scholarly journals Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines

2019 ◽  
Vol 400 (9) ◽  
pp. 1129-1139 ◽  
Author(s):  
Iryna Hlushchenko ◽  
Pirta Hotulainen
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Signal Molecule ◽  
Brain Functions ◽  
Dendritic Shaft ◽  
Term Potentiation

Abstract Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.

scholarly journals Inhibition promotes long-term potentiation at cerebellar excitatory synapses

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
F. Binda ◽  
K. Dorgans ◽  
S. Reibel ◽  
K. Sakimura ◽  
M. Kano ◽  
...  
Keyword(s):  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Term Potentiation

Calcium: A Trigger for Long-Term Depression and Potentiation in the Hippocampus

Physiology ◽  
1994 ◽  
Vol 9 (6) ◽  
pp. 256-260
Author(s):  
D Debanne ◽  
SM Thompson
Keyword(s):  
Protein Kinases ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Synaptic Strength ◽  
Excitatory Synapses ◽  
Long Term Depression ◽  
Aspartate Receptor ◽  
Term Potentiation ◽  
Different Levels

Two opposing types of plasticity at excitatory synapses in the hippocampus, long-term potentiation and depression, require N-methyl-D-aspartate receptor activation and Ca2+ influx for their induction.The direction of the change in synaptic strength is determined by a balance between phosphorylation and dephosphorylation, as regulated by protein kinases and phosphatases that are activated selectively by different levels of intracellular Ca2+.

Postsynaptic Application of a cAMP Analogue Reverses Long-Term Potentiation in Hippocampal CA1 Pyramidal Neurons

2002 ◽  
Vol 87 (6) ◽  
pp. 3018-3032 ◽  
Author(s):  
Nikolai Otmakhov ◽  
John E. Lisman
Keyword(s):  
Molecular Mechanisms ◽  
Competitive Inhibition ◽  
Drug Application ◽  
Specific Effect ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Camp Analogue ◽  
And Control ◽  
Dependent Processes

The molecular mechanisms that underlie the maintenance of long-term potentiation (LTP) remain unclear. We have examined the influence of postsynaptic cAMP-dependent processes on LTP maintenance in CA1 hippocampal cells. After LTP induction, drugs affecting cAMP-dependent processes were perfused into the cell through a patch pipette. A cAMP analogue, Rp-cAMPS (4 mM), dramatically decreased the amplitude of potentiated synaptic responses. The amplitude of responses in the control pathway was also decreased but to a lesser extent, indicating a specific effect on the potentiation process. This specific effect was not due to the larger amplitude of potentiated responses, was not use-dependent and, unlike other factors that affect LTP maintenance, did not depend on the delay (2, 10, or 25 min) of drug application after LTP induction. Lower concentrations of Rp-cAMPS (1.0 and 0.4 mM) also produced an inhibitory effect but reduced the LTP and control pathways comparably. One possible action of Rp-cAMPS is competitive inhibition of protein kinase A (PKA). Surprisingly, a potent and noncompetitive PKA inhibitor, regulatory type II subunit of PKA, produced only a weak depression of potentiated and control responses indicating there must be other targets for Rp-cAMPS. Moreover, Sp-8-OH-cAMPS, which is an activator of PKA, and Rp-8-OH-cAMPS, which is a weak inhibitor of PKA, both produced effects similar to those of Rp-cAMPS. We conclude that there are postsynaptic cyclic nucleotide-dependent processes that can specifically alter the mechanisms that maintain LTP and that are not primarily dependent on PKA.

Differential effect of FHM2 mutation on synaptic plasticity in distinct hippocampal regions

Cephalalgia ◽  
2019 ◽  
Vol 39 (10) ◽  
pp. 1333-1338 ◽  
Author(s):  
Antonio de Iure ◽  
Petra Mazzocchetti ◽  
Guendalina Bastioli ◽  
Barbara Picconi ◽  
Cinzia Costa ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Familial Hemiplegic Migraine ◽  
Loss Of Function ◽  
Hemiplegic Migraine ◽  
Term Potentiation ◽  
Atp1a2 Gene ◽  
Ca1 Area ◽  
Reduced Rate

Introduction Familial hemiplegic migraine 2 is a pathology linked to mutation of the ATP1A2 gene producing loss of function of the α2 Na+/K+-ATPase (NKA). W887R/+ knock-in (KI) mice are used to model the familial hemiplegic migraine 2 condition and are characterized by 50% reduced NKA expression in the brain and reduced rate of K+ and glutamate clearance by astrocytes. These alterations might, in turn, produce synaptic changes in synaptic transmission and plasticity. Memory and learning deficits observed in familial hemiplegic migraine patients could be ascribed to a possible alteration of hippocampal neuronal plasticity and measuring possible changes of long-term potentiation in familial hemiplegic migraine 2 KI mice might provide insights to strengthen this link. Results Here we have investigated synaptic plasticity in distinct hippocampal regions in familial hemiplegic migraine 2 KI mice. We show that the dentate gyrus long-term potentiation of familial hemiplegic migraine 2 mice is abnormally increased in comparison with control animals. Conversely, in the CA1 area, KI and WT mice express long-term potentiation of similar amplitude. Conclusions The familial hemiplegic migraine 2 KI mice show region-dependent hippocampal plasticity abnormality, which might underlie some of the memory deficits observed in familial migraine.

scholarly journals Inducible molecular switches for the study of long-term potentiation

2003 ◽  
Vol 358 (1432) ◽  
pp. 797-804 ◽  
Author(s):  
Gaël Hédou ◽  
Isabelle M. Mansuy
Keyword(s):  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Knock Out ◽  
Technical Developments ◽  
Term Potentiation ◽  
Dependent Protein ◽  
Strength And Plasticity ◽  
Regulated Gene Expression ◽  
Molecular Bases

This article reviews technical and conceptual advances in unravelling the molecular bases of long-term potentiation (LTP), learning and memory using genetic approaches. We focus on studies aimed at testing a model suggesting that protein kinases and protein phosphatases balance each other to control synaptic strength and plasticity. We describe how gene ‘knock-out’ technology was initially exploited to disrupt the Ca 2+ /calmodulin-dependent protein kinase II α (CaMKII α ) gene and how refined knock-in techniques later allowed an analysis of the role of distinct phosphorylation sites in CaMKII. Further to gene recombination, regulated gene expression using the tetracycline-controlled transactivator and reverse tetracycline-controlled transactivator systems, a powerful new means for modulating the activity of specific molecules, has been applied to CaMKII α and the opposing protein phosphatase calcineurin. Together with electro-physiological and behavioural evaluation of the engineered mutant animals, these genetic methodologies have helped gain insight into the molecular mechanisms of plasticity and memory. Further technical developments are, however, awaited for an even higher level of finesse.

scholarly journals Chronic Fluoxetine Treatment Induces Brain Region-Specific Upregulation of Genes Associated with BDNF-Induced Long-Term Potentiation

2007 ◽  
Vol 2007 ◽  
pp. 1-9 ◽  
Author(s):  
Maria Nordheim Alme ◽  
Karin Wibrand ◽  
Grethe Dagestad ◽  
Clive R. Bramham
Keyword(s):  
Dentate Gyrus ◽  
Brain Region ◽  
Molecular Mechanisms ◽  
Antidepressant Treatment ◽  
Antidepressant Drugs ◽  
Long Term Potentiation ◽  
Specific Pattern ◽  
Early Gene ◽  
Term Potentiation

Several lines of evidence implicate BDNF in the pathogenesis of stress-induced depression and the delayed efficacy of antidepressant drugs. Antidepressant-induced upregulation of BDNF signaling is thought to promote adaptive neuronal plasticity through effects on gene expression, but the effector genes downstream of BDNF has not been identified. Local infusion of BDNF into the dentate gyrus induces a long-term potentiation (BDNF-LTP) of synaptic transmission that requires upregulation of the immediate early gene Arc. Recently, we identified five genes (neuritin, Narp, TIEG1, Carp, and Arl4d) that are coupregulated with Arc during BDNF-LTP. Here, we examined the expression of these genes in the dentate gyrus, hippocampus proper, and prefrontal cortex after antidepressant treatment. We show that chronic, but not acute, fluoxetine administration leads to upregulation of these BDNF-LTP-associated genes in a brain region-specific pattern. These findings link chronic effects of antidepressant treatment to molecular mechanisms underlying BDNF-induced synaptic plasticity.

scholarly journals Activity-Induced Long-Term Potentiation of Excitatory Synapses in Developing Zebrafish Retina In Vivo

Neuron ◽  
2012 ◽  
Vol 75 (3) ◽  
pp. 479-489 ◽  
Author(s):  
Hong-ping Wei ◽  
Yuan-yuan Yao ◽  
Rong-wei Zhang ◽  
Xiao-feng Zhao ◽  
Jiu-lin Du
Keyword(s):  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Term Potentiation

scholarly journals Dissecting the Roles of Kalirin-7/PSD95/GluN2B Interactions in Different Forms of Synaptic Plasticity

2019 ◽  
Author(s):  
Mason L. Yeh ◽  
Jessica R. Yasko ◽  
Eric S. Levine ◽  
Betty A. Eipper ◽  
Richard E. Mains
Keyword(s):  
Synaptic Plasticity ◽  
Knockout Mice ◽  
Molecular Mechanisms ◽  
Postsynaptic Density ◽  
Long Term Potentiation ◽  
Surface Expression ◽  
Multiple Components ◽  
Term Potentiation ◽  
Knockout Animals

AbstractKalirin-7 (Kal7) is a Rac1/RhoG GEF and multidomain scaffold localized to the postsynaptic density which plays an important role in synaptic plasticity. Behavioral and physiological phenotypes observed in the Kal7 knockout mouse are quite specific: genetics of breeding, growth, strength and coordination are normal; Kal7 knockout animals self-administer cocaine far more than normal mice, show exaggerated locomotor responses to cocaine, but lack changes in dendritic spine morphology seen in wildtype mice; Kal7 knockout mice have depressed surface expression of GluN2B receptor subunits and exhibit marked suppression of long-term potentiation and depression in hippocampus, cerebral cortex, and spinal cord; and Kal7 knockout mice have dramatically blunted perception of pain. To address the underlying cellular and molecular mechanisms which are deranged by loss of Kal7, we administered intracellular blocking peptides to acutely change Kal7 function at the synapse, to determine if plasticity deficits in Kal7-/-mice are the product of developmental processes since conception, or could be detected on a much shorter time scale. We found that specific disruption of the interactions of Kal7 with PSD-95 or GluN2B resulted in significant suppression of long-term potentiation and long-term depression. Biochemical approaches indicated that Kal7 interacted with PSD-95 at multiple sites within Kal7.Graphical Table of ContentsThe postsynaptic density is an integral player in receiving, interpreting and storing signals transmitted by presynaptic terminals. The correct molecular composition is crucial for successful expression of synaptic plasticity. Key components of the postsynaptic density include ligand-gated ion channels, structural and binding proteins, and multidomain scaffolding plus enzymatic proteins. These studies address whether the multiple components of the synaptic density bind together in a static or slowly adapting molecular complex, or whether critical interactions are fluid on a minute-to-minute basis.

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