scholarly journals IL-33 Acts to Express Schaffer Collateral/CA1 LTP and Regulate Learning and Memory by Targeting MyD88

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Tomoyuki Nishizaki
Keyword(s):  
Learning And Memory ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Spatial Learning And Memory ◽  
Dependent Manner ◽  
Wild Type ◽  
Schaffer Collateral ◽  
Deficient Mice ◽  
Wild Type Control

Interleukin-33 (IL-33) is recognized to transmit a signal through a heterodimeric receptor complex ST2/interleukin-1 receptor accessory protein (IL-1RAcP) bearing activation of myeloid differentiation factor 88 (MyD88). High-frequency stimulation to the Schaffer collateral induced long-term potentiation (LTP) in the CA1 region of hippocampal slices from wild-type control mice. Schaffer collateral/CA1 LTP in IL-33-deficient mice was significantly suppressed, which was neutralized by application with IL-33. Similar suppression of the LTP was found with MyD88-deficient mice but not with ST2-deficient mice. In the water maze test, the acquisition latency in IL-33-deficient and MyD88-deficient mice was significantly prolonged as compared with that in wild-type control mice. Moreover, the retention latency in MyD88-deficient mice was markedly prolonged. In contrast, the acquisition and retention latencies in ST2-deficient mice were not affected. Taken together, these results show that IL-33 acts to express Schaffer collateral/CA1 LTP relevant to spatial learning and memory in a MyD88-dependent manner and that the LTP might be expressed through an IL-1R1/IL-1RAcP-MyD88 pathway in the absence of ST2.

Attenuated LTP in Hippocampal Dentate Gyrus Neurons of Mice Deficient in the PAF Receptor

2001 ◽  
Vol 85 (1) ◽  
pp. 384-390 ◽  
Author(s):  
Chu Chen ◽  
Jeffrey C. Magee ◽  
Victor Marcheselli ◽  
Mattie Hardy ◽  
Nicolas G. Bazan
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Wild Type ◽  
In The Wild ◽  
Paf Receptor ◽  
Deficient Mice

Platelet-activating factor (PAF), a bioactive lipid (1- O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) derived from phospholipase A2and other pathways, has been implicated in neural plasticity and memory formation. Long-term potentiation (LTP) can be induced by the application of PAF and blocked by a PAF receptor (PAF-R) inhibitor in the hippocampal CA1 and dentate gyrus. To further investigate the role of PAF in synaptic plasticity, we compared LTP in dentate granule cells from hippocampal slices of adult mice deficient in the PAF-R and their age-matched wild-type littermates. Whole cell patch-clamp recordings were made in the current-clamp mode. LTP in the perforant path was induced by a high-frequency stimulation (HFS) and defined as >20% increase above baseline of the amplitude of excitatory postsynaptic potentials (EPSPs) from 26 to 30 min after HFS. HFS-induced enhancement of the EPSP amplitude was attenuated in cells from the PAF-R-deficient mice (163 ± 14%, mean ± SE; n = 32) when compared with that in wild-type mice (219 ± 17%, n = 32). The incidence of LTP induction was also lower in the cells from the deficient mice (72%, 23 of 32 cells) than in the wild-type mice (91%, 29 of 32 cells). Using paired-pulse facilitation as a synaptic pathway discrimination, it appeared that there were differences in LTP magnitudes in the lateral perforant path but not in the medial perforant path between the two groups. BN52021 (5 μM), a PAF synaptosomal receptor antagonist, reduced LTP in the lateral path in the wild-type mice. However, neither BN52021, nor BN50730 (5 μM), a microsomal PAF-R antagonist, reduced LTP in the lateral perforant path in the receptor-deficient mice. These data provide evidence that PAF-R-deficient mice are a useful model to study LTP in the dentate gyrus and support the notion that PAF actively participates in hippocampal synaptic plasticity.

scholarly journals Impairment of Spike-Timing-Dependent Plasticity at Schaffer Collateral-CA1 Synapses in Adult APP/PS1 Mice Depends on Proximity of Aβ Plaques

2021 ◽  
Vol 22 (3) ◽  
pp. 1378
Author(s):  
Machhindra Garad ◽  
Elke Edelmann ◽  
Volkmar Leßmann
Keyword(s):  
Neurodegenerative Disorder ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Spike Timing ◽  
Dependent Manner ◽  
Spike Timing Dependent Plasticity ◽  
Schaffer Collateral ◽  
Ca1 Neurons ◽  
Dependent Plasticity ◽  
The Impact

Alzheimer’s disease (AD) is a multifaceted neurodegenerative disorder characterized by progressive and irreversible cognitive decline, with no disease-modifying therapy until today. Spike timing-dependent plasticity (STDP) is a Hebbian form of synaptic plasticity, and a strong candidate to underlie learning and memory at the single neuron level. Although several studies reported impaired long-term potentiation (LTP) in the hippocampus in AD mouse models, the impact of amyloid-β (Aβ) pathology on STDP in the hippocampus is not known. Using whole cell patch clamp recordings in CA1 pyramidal neurons of acute transversal hippocampal slices, we investigated timing-dependent (t-) LTP induced by STDP paradigms at Schaffer collateral (SC)-CA1 synapses in slices of 6-month-old adult APP/PS1 AD model mice. Our results show that t-LTP can be induced even in fully developed adult mice with different and even low repeat STDP paradigms. Further, adult APP/PS1 mice displayed intact t-LTP induced by 1 presynaptic EPSP paired with 4 postsynaptic APs (6× 1:4) or 1 presynaptic EPSP paired with 1 postsynaptic AP (100× 1:1) STDP paradigms when the position of Aβ plaques relative to recorded CA1 neurons in the slice were not considered. However, when Aβ plaques were live stained with the fluorescent dye methoxy-X04, we observed that in CA1 neurons with their somata <200 µm away from the border of the nearest Aβ plaque, t-LTP induced by 6× 1:4 stimulation was significantly impaired, while t-LTP was unaltered in CA1 neurons >200 µm away from plaques. Treatment of APP/PS1 mice with the anti-inflammatory drug fingolimod that we previously showed to alleviate synaptic deficits in this AD mouse model did not rescue the impaired t-LTP. Our data reveal that overexpression of APP and PS1 mutations in AD model mice disrupts t-LTP in an Aβ plaque distance-dependent manner, but cannot be improved by fingolimod (FTY720) that has been shown to rescue conventional LTP in CA1 of APP/PS1 mice.

scholarly journals The Effect of Electroacupuncture versus Manual Acupuncture through the Expression of TrkB/NF-κB in the Subgranular Zone of the Dentate Gyrus of Telomerase-Deficient Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Dong Lin ◽  
Jie Zhang ◽  
Wanyu Zhuang ◽  
Xiaodan Yan ◽  
Xiaoting Yang ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning And Memory ◽  
Manual Acupuncture ◽  
Wild Type ◽  
Age Related ◽  
Bdnf Signaling ◽  
Electric Acupuncture ◽  
Neurotropic Factor ◽  
The Brain ◽  
Deficient Mice

Our previous study showed that the acupuncture stimulation on the acupoint (ST-36) could activate the brain-derived neurotropic factor (BDNF) signaling pathways in telomerase-deficient mice. Recently, we set out to investigate whether the manual acupuncture (MA) or electroacupuncture (EA) displays a therapeutic advantage on age-related deterioration of learning and memory. Both telomerase-deficient mice (Terc−/− group, n=24) and wild-type mice (WT group, n=24) were randomly assigned to 3 subgroups (CON, controls with no treatment; MA, mice receiving manual acupuncture; EA, mice receiving electric acupuncture). The mice were subjected to behavior test, and EA/MA were applied at bilateral acupoints (ST36) 30 min daily for 7 successive days. The brain tissues were collected after the last Morris water maze (MWM) test and were subjected to the immunohistochemistry and western blot analysis. The MWM test showed that EA can significantly increase the time in target quadrant (P≤0.01) and frequency of locating platform for Terc−/− mice (P≤0.05), while nothing changed in WT mice. Furthermore, western blotting and immunohistochemistry suggested that EA could also specifically increase the expression of TrkB and NF-κB in Terc−/− mice but not in wild-type mice (P≤0.05). Meanwhile, the expression level and ratio of ERK/p-ERK did not exhibit significant changes in each subgroup. These results indicated that, compared with MA, the application of EA could specifically ameliorate the spatial learning and memory capability for telomerase-deficient mice through the activation of TrkB and NF-κB.

scholarly journals Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hieu Hoang Trung ◽  
Toru Yoshihara ◽  
Akito Nakao ◽  
Katsumi Hayashida ◽  
Yoshiki Hirata ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fear Conditioning ◽  
Open Field ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Regulatory Subunit ◽  
Type I ◽  
Schaffer Collateral ◽  
Normal Behavior ◽  
Collateral Pathway

AbstractThe RIβ subunit of cAMP-dependent protein kinase (PKA), encoded by Prkar1b, is a neuronal isoform of the type I regulatory subunit of PKA. Mice lacking the RIβ subunit exhibit normal long-term potentiation (LTP) in the Schaffer collateral pathway of the hippocampus and normal behavior in the open-field and fear conditioning tests. Here, we combined genetic, electrophysiological, and behavioral approaches to demonstrate that the RIβ subunit was involved in body tremor, LTP in the Schaffer collateral pathway, and fear conditioning memory in rats. Genetic analysis of WTC-furue, a mutant strain with spontaneous tremors, revealed a deletion in the Prkar1b gene of the WTC-furue genome. Prkar1b-deficient rats created by the CRISPR/Cas9 system exhibited body tremor. Hippocampal slices from mutant rats showed deficient LTP in the Schaffer collateral–CA1 synapse. Mutant rats also exhibited decreased freezing time following contextual and cued fear conditioning, as well as increased exploratory behavior in the open field. These findings indicate the roles of the RIβ subunit in tremor pathogenesis and contextual and cued fear memory, and suggest that the hippocampal and amygdala roles of this subunit differ between mice and rats and that rats are therefore beneficial for exploring RIβ function.

scholarly journals Imaging spatio-temporal patterns of long-term potentiation in mouse hippocampus

2003 ◽  
Vol 358 (1432) ◽  
pp. 689-693 ◽  
Author(s):  
Toshiyuki Hosokawa ◽  
Masaki Ohta ◽  
Takeshi Saito ◽  
Alan Fine
Keyword(s):  
Hippocampal Slices ◽  
Temporal Patterns ◽  
Long Term Potentiation ◽  
Optical Recording ◽  
Stratum Radiatum ◽  
High Frequency Stimulation ◽  
Optical Signals ◽  
Term Potentiation ◽  
Spatio Temporal

Spatio-temporal patterns of neuronal activity before and after the induction of long-term potentiation in mouse hippocampal slices were studied using a real-time high-resolution optical recording system. After staining the slices with voltage-sensitive dye, transmitted light images and extracellular field potentials were recorded in response to stimuli applied to CA1 stratum radiatum. Optical and electrical signals in response to single test pulses were enhanced for at least 30 minutes after brief high-frequency stimulation at the same site. In two-pathway experiments, potentiation was restricted to the tetanized pathway. The optical signals demonstrated that both the amplitude and area of the synaptic response were increased, in patterns not predictable from the initial, pretetanus, pattern of activation. Optical signals will be useful for investigating spatio-temporal patterns of synaptic enhancement underlying information storage in the brain.

2.45 GHz microwave radiation impairs learning, memory, and hippocampal synaptic plasticity in the rat

2018 ◽  
Vol 34 (12) ◽  
pp. 873-883 ◽  
Author(s):  
Narges Karimi ◽  
Mahnaz Bayat ◽  
Masoud Haghani ◽  
Hamed Fahandezh Saadi ◽  
Gholam Reza Ghazipour
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Continuous Wave ◽  
Glutamate Release ◽  
Average Power ◽  
Field Potential ◽  
Long Term Potentiation ◽  
Whole Body ◽  
Spatial Learning And Memory ◽  
Hippocampal Synaptic Plasticity

Microwave (MW) radiation has a close relationship with neurobehavioral disorders. Due to the widespread usage of MW radiation, especially in our homes, it is essential to investigate the direct effect of MW radiation on the central nervous system. Therefore, this study was carried out to determine the effect of MW radiation on memory and hippocampal synaptic plasticity. The rats were exposed to 2.45 GHz MW radiation (continuous wave with overall average power density of 0.016 mW/cm2 and overall average whole-body specific absorption rate value of 0.017 W/kg) for 2 h/day over a period of 40 days. Spatial learning and memory were tested by radial maze and passive avoidance tests. We evaluated the synaptic plasticity and hippocampal neuronal cells number by field potential recording and Giemsa staining, respectively. Our results showed that MW radiation exposure decreased the learning and memory performance that was associated with decrement of long-term potentiation induction and excitability of CA1 neurons. However, MW radiation did not have any effects on short-term plasticity and paired-pulse ratio as a good indirect index for measurement of glutamate release probability. The evaluation of hippocampal morphology indicated that the neuronal density in the hippocampal CA1 area was significantly decreased by MW.

scholarly journals Tripchlorolide May Improve Spatial Cognition Dysfunction and Synaptic Plasticity after Chronic Cerebral Hypoperfusion

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Zhao-Hui Yao ◽  
Xiao-li Yao ◽  
Shao-feng Zhang ◽  
Ji-chang Hu ◽  
Yong Zhang
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Long Term Potentiation ◽  
Chronic Cerebral Hypoperfusion ◽  
Synaptic Proteins ◽  
Cerebral Hypoperfusion ◽  
Spatial Learning And Memory ◽  
Pathophysiological Mechanism

Chronic cerebral hypoperfusion (CCH) is a common pathophysiological mechanism that underlies cognitive decline and degenerative processes in dementia and other neurodegenerative diseases. Low cerebral blood flow (CBF) during CCH leads to disturbances in the homeostasis of hemodynamics and energy metabolism, which in turn results in oxidative stress, astroglia overactivation, and synaptic protein downregulation. These events contribute to synaptic plasticity and cognitive dysfunction after CCH. Tripchlorolide (TRC) is an herbal compound with potent neuroprotective effects. The potential of TRC to improve CCH-induced cognitive impairment has not yet been determined. In the current study, we employed behavioral techniques, electrophysiology, Western blotting, immunofluorescence, and Golgi staining to investigate the effect of TRC on spatial learning and memory impairment and on synaptic plasticity changes in rats after CCH. Our findings showed that TRC could rescue CCH-induced spatial learning and memory dysfunction and improve long-term potentiation (LTP) disorders. We also found that TRC could prevent CCH-induced reductions in N-methyl-D-aspartic acid receptor 2B, synapsin I, and postsynaptic density protein 95 levels. Moreover, TRC upregulated cAMP-response element binding protein, which is an important transcription factor for synaptic proteins. TRC also prevented the reduction in dendritic spine density that is caused by CCH. However, sham rats treated with TRC did not show any improvement in cognition. Because CCH causes disturbances in brain energy homeostasis, TRC therapy may resolve this instability by correcting a variety of cognitive-related signaling pathways. However, for the normal brain, TRC treatment led to neither disturbance nor improvement in neural plasticity. Additionally, this treatment neither impaired nor further improved cognition. In conclusion, we found that TRC can improve spatial learning and memory, enhance synaptic plasticity, upregulate the expression of some synaptic proteins, and increase the density of dendritic spines. Our findings suggest that TRC may be beneficial in the treatment of cognitive impairment induced by CCH.

Trif is not required for immune complex glomerulonephritis: dying cells activate mesangial cells via Tlr2/Myd88 rather than Tlr3/Trif

2009 ◽  
Vol 296 (4) ◽  
pp. F867-F874 ◽  
Author(s):  
Julia Lichtnekert ◽  
Volker Vielhauer ◽  
Daniel Zecher ◽  
Onkar P. Kulkarni ◽  
Sebastian Clauss ◽  
...  
Keyword(s):  
Mesangial Cells ◽  
Apoptotic Cell ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Wild Type ◽  
Tlr Agonists ◽  
Rabbit Igg ◽  
Dying Cells ◽  
Myd88 Signaling ◽  
Deficient Mice

Viral RNA or bacterial products can activate glomerular mesangial cells via a subset of Toll-like receptors (Tlr). Because Tlr2-deficient mice were recently found to have attenuated nephrotoxic serum nephritis (NSN), we hypothesized that endogenous Tlr agonists can activate glomerular mesangial cells. Primary mesangial cells from C57BL/6 mice expressed Tlr1-6 and Tlr11 mRNA at considerable levels and produced Il-6 when being exposed to the respective Tlr ligands. Exposure to necrotic cells activated cultured primary mesangial cells to produce Il-6 in a Tlr2/Myd88-dependent manner. Apoptotic cells activated cultured mesangial cells only when being enriched to high numbers. Apoptotic cell-induced Il-6 release was Myd88 dependent, and only purified apoptotic cell RNA induced Trif signaling in mesangial cells. Does Trif signaling contribute to disease activity in glomerulonephritis? To answer this question, we induced autologous NSN by injection of NS raised in rabbits in Trif-mutant and wild-type mice. Lack of Trif did not alter the functional and histomorphological abnormalities of NSN, including the evolution of anti-rabbit IgG and anti-rabbit-specific nephritogenic T cells. We therefore conclude that apoptotic cell RNA is a poor activator of Trif signaling in mesangial cells and that necrotic cells' releases rather activate mesangial cells via the Tlr2/Myd88 signaling pathway.

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