[P3-141]: FOLATE PREVENTS THE DETRIMENTAL EFFECTS OF OLIGOMERIC Aβ ON INSULIN RECEPTOR LOCALIZATION AND FUNCTION AND LONG-TERM POTENTIATION

2017 ◽  
Vol 13 (7S_Part_20) ◽  
pp. P989-P989
Author(s):  
Athena Ching Jung Wang ◽  
Ron Freund ◽  
Christina M. Coughlan ◽  
Esteban M. Lucero ◽  
Mark DellAcqua ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Long Term Potentiation ◽  
Receptor Localization ◽  
Term Potentiation ◽  
And Function

scholarly journals Astrocytes dystrophy in ageing brain parallels impaired synaptic plasticity

2020 ◽  
Author(s):  
Alexander Popov ◽  
Alexey Brazhe ◽  
Pavel Denisov ◽  
Oksana Sutyagina ◽  
Natalia Lazareva ◽  
...  
Keyword(s):  
Volume Fraction ◽  
Long Term Potentiation ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
Age Dependent ◽  
And Function ◽  
The Impact

Little is known about age-dependent changes in structure and function of astrocytes and of the impact of these into the cognitive decline in the senescent brain. The prevalent view on age-dependent increase in reactive astrogliosis and astrocytic hypertrophy requires scrutiny and detailed analysis. Using two-photon microscopy in conjunction with 3D reconstruction, Sholl and volume fraction analysis we demonstrate a significant reduction in the number and the length of astrocytic processes, in astrocytic territorial domains and in astrocyte-to-astrocyte coupling in the aged brain. Probing physiology of astrocytes with patch-clamp and Ca2+ imaging revealed deficits in K+ and glutamate clearance, and spatiotemporal reorganization of Ca2+ events in old astrocytes. These changes paralleled impaired synaptic long-term potentiation (LTP) in hippocampal CA1 in old mice. Our findings may explain astroglial mechanisms of age-dependent decline in learning and memory.

scholarly journals Brevican-Deficient Mice Display Impaired Hippocampal CA1 Long-Term Potentiation but Show No Obvious Deficits in Learning and Memory

2002 ◽  
Vol 22 (21) ◽  
pp. 7417-7427 ◽  
Author(s):  
Cord Brakebusch ◽  
Constanze I. Seidenbecher ◽  
Fredrik Asztely ◽  
Uwe Rauch ◽  
Henry Matthies ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Long Term Potentiation ◽  
Brain Anatomy ◽  
Perineuronal Nets ◽  
Functional Roles ◽  
Term Potentiation ◽  
And Function ◽  
Deficient Mice

ABSTRACT Brevican is a brain-specific proteoglycan which is found in specialized extracellular matrix structures called perineuronal nets. Brevican increases the invasiveness of glioma cells in vivo and has been suggested to play a role in central nervous system fiber tract development. To study the role of brevican in the development and function of the brain, we generated mice lacking a functional brevican gene. These mice are viable and fertile and have a normal life span. Brain anatomy was normal, although alterations in the expression of neurocan were detected. Perineuronal nets formed but appeared to be less prominent in mutant than in wild-type mice. Brevican-deficient mice showed significant deficits in the maintenance of hippocampal long-term potentiation (LTP). However, no obvious impairment of excitatory and inhibitory synaptic transmission was found, suggesting a complex cause for the LTP defect. Detailed behavioral analysis revealed no statistically significant deficits in learning and memory. These data indicate that brevican is not crucial for brain development but has restricted structural and functional roles.

scholarly journals Stress enhances fear by forming new synapses with greater capacity for long-term potentiation in the amygdala

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130151 ◽  
Author(s):  
Aparna Suvrathan ◽  
Sharath Bennur ◽  
Supriya Ghosh ◽  
Anupratap Tomar ◽  
Shobha Anilkumar ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Conditioned Fear ◽  
Brain Area ◽  
Long Term Potentiation ◽  
Silent Synapses ◽  
Term Potentiation ◽  
Emotional Behaviour ◽  
Synaptic Changes ◽  
And Function

Prolonged and severe stress leads to cognitive deficits, but facilitates emotional behaviour. Little is known about the synaptic basis for this contrast. Here, we report that in rats subjected to chronic immobilization stress, long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated synaptic responses are enhanced in principal neurons of the lateral amygdala, a brain area involved in fear memory formation. This is accompanied by electrophysiological and morphological changes consistent with the formation of ‘silent synapses’, containing only NMDARs. In parallel, chronic stress also reduces synaptic inhibition. Together, these synaptic changes would enable amygdalar neurons to undergo further experience-dependent modifications, leading to stronger fear memories. Consistent with this prediction, stressed animals exhibit enhanced conditioned fear. Hence, stress may leave its mark in the amygdala by generating new synapses with greater capacity for plasticity, thereby creating an ideal neuronal substrate for affective disorders. These findings also highlight the unique features of stress-induced plasticity in the amygdala that are strikingly different from the stress-induced impairment of structure and function in the hippocampus.

scholarly journals Differences in GluN2B-containing NMDA receptors result in opposite long-term plasticity and dopaminergic modulation at ipsilateral vs. contralateral cortico-striatal synapses

2019 ◽  
Author(s):  
Wei Li ◽  
Lucas Pozzo-Miller
Keyword(s):  
Synaptic Plasticity ◽  
Primary Motor Cortex ◽  
Glutamate Transporter ◽  
Long Term Potentiation ◽  
D1 Receptors ◽  
Synaptic Structure ◽  
Term Potentiation ◽  
Nmdar Subunit ◽  
And Function

AbstractExcitatory neurons in the primary motor cortex project bilaterally to the striatum. However, whether synaptic structure and function in ipsilateral and contralateral cortico-striatal pathways is identical or different remains largely unknown. Here, we describe that excitatory synapses in the contralateral pathway have higher levels of NMDA-type of glutamate receptors (NMDARs) than those in the ipsilateral pathway, although both synapses utilize the same presynaptic vesicular glutamate transporter. We also show that NMDARs containing the GluN2B subunit, but not GluN2A, contribute to this difference. The altered NMDAR subunit composition in these two pathways results in opposite synaptic plasticity: long-term depression in the ipsilateral pathway and long-term potentiation in the contralateral pathway. Furthermore, we demonstrate that activation of D1 and D2 dopamine (DA) receptors by either selective pharmacological agonists or light-induced release of endogenous DA have no effect on NMDAR-mediated neurotransmission in either pathway. However, blocking basal DAergic tone with either D1 or D2 with selective antagonists revealed that GluN2B-containing NMDARs are modulated by D1 receptors in the contralateral pathway and by D2 receptors in the ipsilateral pathway. Such distinct modulatory actions seem to be permissive rather than sufficient for the induction of long-term synaptic plasticity. Altogether, our results provide novel and unexpected evidence for the lack of bilaterality of NMDAR-mediated synaptic transmission at cortico-striatal pathways due to differences in the expression of GluN2B subunits, which results in differences in bidirectional synaptic plasticity and modulation by dopaminergic inputs.

scholarly journals Synaptic plasticity and cognitive function are disrupted in the absence of Lrp4

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Andrea M Gomez ◽  
Robert C Froemke ◽  
Steven J Burden
Keyword(s):  
Long Term Potentiation ◽  
Neurological Deficits ◽  
Spine Density ◽  
Ca1 Neurons ◽  
Form And Function ◽  
Term Potentiation ◽  
Hippocampal Ca3 ◽  
And Function ◽  
Apical Dendrites

Lrp4, the muscle receptor for neuronal Agrin, is expressed in the hippocampus and areas involved in cognition. The function of Lrp4 in the brain, however, is unknown, as Lrp4−/− mice fail to form neuromuscular synapses and die at birth. Lrp4−/− mice, rescued for Lrp4 expression selectively in muscle, survive into adulthood and showed profound deficits in cognitive tasks that assess learning and memory. To learn whether synapses form and function aberrantly, we used electrophysiological and anatomical methods to study hippocampal CA3–CA1 synapses. In the absence of Lrp4, the organization of the hippocampus appeared normal, but the frequency of spontaneous release events and spine density on primary apical dendrites were reduced. CA3 input was unable to adequately depolarize CA1 neurons to induce long-term potentiation. Our studies demonstrate a role for Lrp4 in hippocampal function and suggest that patients with mutations in Lrp4 or auto-antibodies to Lrp4 should be evaluated for neurological deficits.

scholarly journals Ultrastructure of light-activated axons following optogenetic stimulation to produce late-phase long-term potentiation

2019 ◽  
Author(s):  
Masaaki Kuwajima ◽  
Olga I. Ostrovskaya ◽  
Guan Cao ◽  
Seth A. Weisberg ◽  
Kristen M. Harris ◽  
...  
Keyword(s):  
Late Phase ◽  
Long Term Potentiation ◽  
State Dependent ◽  
Term Potentiation ◽  
Section Electron ◽  
Hippocampal Ca3 ◽  
Ultrastructure And Function ◽  
Ca3 Neurons ◽  
And Function

AbstractAnalysis of neuronal compartments has revealed many state-dependent changes in geometry but establishing synapse-specific mechanisms at the nanoscale has proven elusive. We co-expressed channelrhodopsin2-GFP and mAPEX2 in a subset of hippocampal CA3 neurons and used trains of light to induce late-phase long-term potentiation (L-LTP) in area CA1. L-LTP was shown to be specific to the labeled axons by severing CA3 inputs, which prevented back-propagating recruitment of unlabeled axons. Membrane-associated mAPEX2 tolerated microwave-enhanced chemical fixation and drove tyramide signal amplification to deposit Alexa Fluor dyes in the light-activated axons. Subsequent post-embedding immunogold labeling resulted in outstanding ultrastructure and clear distinctions between labeled (activated), and unlabeled axons without obscuring subcellular organelles. The gold-labeled axons in potentiated slices were reconstructed through serial section electron microscopy; presynaptic vesicles and other constituents could be quantified unambiguously. The genetic specification, reliable physiology, and compatibility with established methods for ultrastructural preservation make this an ideal approach to link synapse ultrastructure and function in intact circuits.

scholarly journals Long-term potentiation in the hippocampus: discovery, mechanisms and function

Neuroforum ◽  
2018 ◽  
Vol 24 (3) ◽  
pp. A103-A120 ◽  
Author(s):  
Tim V.P. Bliss ◽  
Graham L. Collingridge ◽  
Richard G.M. Morris ◽  
Klaus G. Reymann
Keyword(s):  
Learning And Memory ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
And Function

Abstract In this review we reflect upon our contributions to the study of the properties and mechanisms of long-term potentiation (LTP) and describe some of the major influences on our work. We then go on to consider whether LTP has fulfilled its early promise of providing a compelling account of the synaptic basis of learning and memory.

scholarly journals CaMKII holoenzyme mechanisms that govern the LTP versus LTD decision

2021 ◽  
Vol 7 (16) ◽  
pp. eabe2300
Author(s):  
Sarah G. Cook ◽  
Olivia R. Buonarati ◽  
Steven J. Coultrap ◽  
K. Ulrich Bayer
Keyword(s):  
Stimulus Frequency ◽  
Long Term Potentiation ◽  
Inhibitory Synapses ◽  
Brain Functions ◽  
Term Potentiation ◽  
Autonomous Activity ◽  
And Function ◽  
Higher Brain Functions ◽  
Feed Forward Inhibition

Higher brain functions are thought to require synaptic frequency decoding that can lead to long-term potentiation (LTP) or depression (LTD). We show that the LTP versus LTD decision is determined by complex cross-regulation of T286 and T305/306 autophosphorylation within the 12meric CaMKII holoenzyme, which enabled molecular computation of stimulus frequency, amplitude, and duration. Both LTP and LTD require T286 phosphorylation, but T305/306 phosphorylation selectively promoted LTD. In response to excitatory LTP versus LTD stimuli, the differential T305/306 phosphorylation directed CaMKII movement to either excitatory or inhibitory synapses, thereby coordinating plasticity at both synapse types. Fast T305/306 phosphorylation required prior T286 phosphorylation and then curbed CaMKII activity by two mechanisms: (i) a cis-subunit reaction reduced both Ca2+ stimulation and autonomous activity and (ii) a trans-subunit reaction enabled complete activity shutdown and feed-forward inhibition of further T286 phosphorylation. These are fundamental additions to the long-studied CaMKII regulation and function in neuronal plasticity.

scholarly journals Kalirin and Trio proteins serve critical roles in excitatory synaptic transmission and LTP

2016 ◽  
Vol 113 (8) ◽  
pp. 2264-2269 ◽  
Author(s):  
Bruce E. Herring ◽  
Roger A. Nicoll
Keyword(s):  
Ampa Receptor ◽  
Rho Gtpases ◽  
Imaging Techniques ◽  
Long Term Potentiation ◽  
Structure And Function ◽  
Receptor Expression ◽  
Term Potentiation ◽  
And Function ◽  
Necessary And Sufficient

The molecular mechanism underlying long-term potentiation (LTP) is critical for understanding learning and memory. CaMKII, a key kinase involved in LTP, is both necessary and sufficient for LTP induction. However, how CaMKII gives rise to LTP is currently unknown. Recent studies suggest that Rho GTPases are necessary for LTP. Rho GTPases are activated by Rho guanine exchange factors (RhoGEFs), but the RhoGEF(s) required for LTP also remain unknown. Here, using a combination of molecular, electrophysiological, and imaging techniques, we show that the RhoGEF Kalirin and its paralog Trio play critical and redundant roles in excitatory synapse structure and function. Furthermore, we show that CaMKII phosphorylation of Kalirin is sufficient to enhance synaptic AMPA receptor expression, and that preventing CaMKII signaling through Kalirin and Trio prevents LTP induction. Thus, our data identify Kalirin and Trio as the elusive targets of CaMKII phosphorylation responsible for AMPA receptor up-regulation during LTP.

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