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 Reduced Synaptic Plasticity in the Lateral Perforant Path Input to the Dentate Gyrus of Aged C57BL/6 Mice

2003 ◽  
Vol 90 (1) ◽  
pp. 32-38 ◽  
Author(s):  
David J. Froc ◽  
Brennan Eadie ◽  
Amanda M. Li ◽  
Karl Wodtke ◽  
Maric Tse ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Significant Degree ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Synaptic Efficacy ◽  
Term Potentiation ◽  
Effects Of Aging

Hippocampal slices obtained from C57BL/6 mice (3–25 mo) were used to investigate the effects of aging on excitatory postsynaptic potentials (EPSPs) elicited in dentate gyrus with lateral perforant path stimulation. The maximal amplitude of the EPSP, as well as the degree of paired-pulse facilitation, was significantly reduced in animals aged 12 mo or more compared with younger animals (<12 mo). Although all animals showed equivalent short-term potentiation (STP) in response to high-frequency stimulation, this did not translate into a long-lasting increase in synaptic efficacy in the older animals. A significant degree of long-term potentiation (LTP) of synaptic efficacy was only observed in animals <12 mo of age when measured 30 min after induction. Blocking GABAA-mediated inhibition significantly enhanced STP in younger and older animals; however, a significant degree of LTP was again only observed in slices taken from younger animals. These data indicate that the lateral perforant path input to the dentate gyrus is altered by the aging process, and that this results in a reduction in the capacity of this input to exhibit long-lasting synaptic plasticity.

Medial amygdala enhances synaptic transmission and synaptic plasticity in the dentate gyrus of rats in vivo

1995 ◽  
Vol 74 (5) ◽  
pp. 2201-2203 ◽  
Author(s):  
Y. Ikegaya ◽  
K. Abe ◽  
H. Saito ◽  
N. Nishiyama
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Dentate Gyrus ◽  
High Frequency ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Medial Amygdala ◽  
Frequency Stimulation ◽  
Stimulation Of

1. The present experiment was designed to test whether synaptic transmission and synaptic plasticity in the dentate gyrus were modulated by the medial amygdala (MeA). Field potentials in the dentate gyrus (DG) evoked by stimulations of the medial perforant path (PP) were extracellularly recorded in anesthetized rats. 2. Although single-pulse stimulation of the MeA augmented PP stimulation-evoked population spike amplitude in the DG transiently, high-frequency stimulation (100 Hz for 1 s) of the MeA induced long-lasting enhancement of synaptic transmission that was not occluded by PP tetanus-induced long-term potentiation (LTP). 3. When high-frequency stimulation of the MeA was applied concurrently with weak tetanus of the PP, which alone induced only marginal LTP, the magnitude of LTP increased considerably. 4. These results demonstrate that neuron activities in the MeA induce short- and long-lasting changes in the excitability of the PP-DG synapses and thereby enhance their synaptic plasticity.

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.

scholarly journals Forepaw Sensorimotor Deprivation in Early Life Leads to the Impairments on Spatial Memory and Synaptic Plasticity in Rats

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Fei Li ◽  
Xiaohua Cao ◽  
Xingming Jin ◽  
Chonghuai Yan ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Memory ◽  
Learning And Memory ◽  
Early Life ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Sprague Dawley ◽  
Cellular Mechanisms ◽  
Spatial Reference

To investigate the influence of forepaw sensorimotor deprivation on memory and synaptic plasticity, Sprague-Dawley rats were divided into two groups: a sham-operated group and a group deprived of forepaw sensorimotor function by microsurgical operation at postnatal day 13 (PN13). Behavioral and electrophysiological studies were performed at PN25, PN35, PN45, and PN60. Open field test was used to assess the spontaneous locomotor activity. Morris water maze was used to evaluate spatial reference learning and memory. The long-term potentiation (LTP) in the medial perforant path—dentate gyrus (MPP-DG) pathway was examined with hippocampal slices. We found that forepaw sensorimotor deprivation did not affect spontaneous activity of the rats. However, spatial reference learning and memory were significantly impaired in their early life (PN25, PN35, and PN45). In accordance with the behavior results, LTP in MPP-DG pathway was significantly suppressed in their early life. These data demonstrated that forepaw sensorimotor deprivation led to the impairments on spatial memory via inducing pronounced deficits in the MPP-DG pathway to exhibit LTP, one of the major cellular mechanisms underlying learning and memory.

scholarly journals Structural homo- and heterosynaptic plasticity in mature and adult newborn rat hippocampal granule cells

2018 ◽  
Vol 115 (20) ◽  
pp. E4670-E4679 ◽  
Author(s):  
Tassilo Jungenitz ◽  
Marcel Beining ◽  
Tijana Radic ◽  
Thomas Deller ◽  
Hermann Cuntz ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Granule Cells ◽  
Molecular Layer ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Spatial Learning And Memory ◽  
Heterosynaptic Plasticity ◽  
Spine Plasticity

Adult newborn hippocampal granule cells (abGCs) contribute to spatial learning and memory. abGCs are thought to play a specific role in pattern separation, distinct from developmentally born mature GCs (mGCs). Here we examine at which exact cell age abGCs are synaptically integrated into the adult network and which forms of synaptic plasticity are expressed in abGCs and mGCs. We used virus-mediated labeling of abGCs and mGCs to analyze changes in spine morphology as an indicator of plasticity in rats in vivo. High-frequency stimulation of the medial perforant path induced long-term potentiation in the middle molecular layer (MML) and long-term depression in the nonstimulated outer molecular layer (OML). This stimulation protocol elicited NMDA receptor-dependent homosynaptic spine enlargement in the MML and heterosynaptic spine shrinkage in the inner molecular layer and OML. Both processes were concurrently present on individual dendritic trees of abGCs and mGCs. Spine shrinkage counteracted spine enlargement and thus could play a homeostatic role, normalizing synaptic weights. Structural homosynaptic spine plasticity had a clear onset, appearing in abGCs by 28 d postinjection (dpi), followed by heterosynaptic spine plasticity at 35 dpi, and at 77 dpi was equally as present in mature abGCs as in mGCs. From 35 dpi on, about 60% of abGCs and mGCs showed significant homo- and heterosynaptic plasticity on the single-cell level. This demonstration of structural homo- and heterosynaptic plasticity in abGCs and mGCs defines the time course of the appearance of synaptic plasticity and integration for abGCs.

scholarly journals Long-term potentiation expands information content of hippocampal dentate gyrus synapses

2018 ◽  
Vol 115 (10) ◽  
pp. E2410-E2418 ◽  
Author(s):  
Cailey Bromer ◽  
Thomas M. Bartol ◽  
Jared B. Bowden ◽  
Dusten D. Hubbard ◽  
Dakota C. Hanka ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Storage Capacity ◽  
Unit Length ◽  
Long Term Potentiation ◽  
Information Storage ◽  
Perforant Path ◽  
Hippocampal Dentate Gyrus ◽  
Term Potentiation

An approach combining signal detection theory and precise 3D reconstructions from serial section electron microscopy (3DEM) was used to investigate synaptic plasticity and information storage capacity at medial perforant path synapses in adult hippocampal dentate gyrus in vivo. Induction of long-term potentiation (LTP) markedly increased the frequencies of both small and large spines measured 30 minutes later. This bidirectional expansion resulted in heterosynaptic counterbalancing of total synaptic area per unit length of granule cell dendrite. Control hemispheres exhibited 6.5 distinct spine sizes for 2.7 bits of storage capacity while LTP resulted in 12.9 distinct spine sizes (3.7 bits). In contrast, control hippocampal CA1 synapses exhibited 4.7 bits with much greater synaptic precision than either control or potentiated dentate gyrus synapses. Thus, synaptic plasticity altered total capacity, yet hippocampal subregions differed dramatically in their synaptic information storage capacity, reflecting their diverse functions and activation histories.

Heterosynaptic LTD and Depotentiation in the Medial Perforant Path of the Dentate Gyrus in the Freely Moving Rat

1997 ◽  
Vol 77 (2) ◽  
pp. 571-578 ◽  
Author(s):  
Valérie Doyère ◽  
Bolek Srebro ◽  
Serge Laroche
Keyword(s):  
Dentate Gyrus ◽  
High Frequency ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Tetanic Stimulation ◽  
Frequency Stimulation ◽  
Freely Moving ◽  
Stimulation Of

Doyère, Valérie, Bolek Srebro, and Serge Laroche. Heterosynaptic LTD and depotentiation in the medial perforant path of the dentate gyrus in the freely moving rat. J. Neurophysiol. 77: 571–578, 1997. We examined the characteristics of heterosynaptic long-term depression (LTD) and depotentiation of previously established long-term potentiation (LTP) in the medial and lateral entorhinal afferents to the dentate gyrus in the awake rat. Rats were prepared for chronic recording of dentate gyrus evoked potentials to activation of the medial and lateral perforant paths. This study in awake rats confirms that heterosynaptic LTD can be induced at inactive medial perforant path synapses in conjunction with the induction of LTP produced by high-frequency stimulation of the lateral perforant path. This form of LTD was long lasting and reversible by tetanic stimulation delivered to the depressed pathway. In contrast, tetanic stimulation of the medial perforant path had only a small heterosynaptic effect on the lateral pathway, suggesting that the two input pathways to the dentate gyrus are not symmetrical in their ability to induce heterosynaptic LTD. We also examined the ability of high-frequency stimulation of one pathway to produce depotentiation of the other pathway. We found that when LTP was first induced in the medial perforant path, depotentiation was induced heterosynaptically by tetanization of the lateral pathway. Both newly established LTP (30 min) and LTP induced and saturated by repeated tetanic stimulation over several days can be depotentiated heterosynaptically. Moreover, depotentiation of the medial perforant path synapses was found to be linearly correlated with the magnitude of LTP induced in the lateral perforant path synapses, and subsequent tetanic stimulation of the depotentiated medial perforant path restored LTP to an extent that counterbalanced depotentiation. The saturation and repotentiation experiments provide clear support for the conclusion that the rapid reversal of LTP reflects true depotentiation of the medial input. Again, as with heterosynaptic LTD, tetanization of the medial perforant path had little effect on previously induced LTP in the lateral path. These results provide evidence that medial perforant path synapses can be depressed and depotentiated heterosynaptically. They suggest that in the intact rat synaptic changes in the afferents to the dentate gyrus from the lateral entorhinal cortex exert powerful control over ongoing or recent synaptic plasticity in the medial entorhinal afferents.

Low-frequency stimulation of the perforant path produces long-term potentiation in the dentate gyrus of unanesthetized rats

1983 ◽  
Vol 61 (10) ◽  
pp. 1156-1161 ◽  
Author(s):  
R. W. Skelton ◽  
J. J. Miller ◽  
A. G. Phillips
Keyword(s):  
Dentate Gyrus ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Synaptic Efficacy ◽  
Term Potentiation ◽  
Frequency Stimulation ◽  
Stimulation Of

Brief periods of high-frequency stimulation of hippocampal afferents produce long-term potentiation (LTP) of synaptic transmission, but the minimum frequency capable of inducing this alteration in synaptic efficacy has not been specified. The present study used the repeated measurement of input–output curves in the perforant path – dentate gyrus system of freely moving rats to monitor synaptic efficacy and found that stimulation at 0.2 Hz, but not 0.04 Hz produced LTP. These results suggest that the minimum stimulation frequency capable of producing LTP is lower than previously described. Possible reasons for the discrepancy between the present and previous findings are discussed, along with the implications of low-frequency potentiation.

BDNF and Control of Synaptic Plasticity in the Adult Brain

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
C. Bramham
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Antidepressant Drugs ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Adult Brain ◽  
Early Gene ◽  
Perforant Path ◽  
Mammalian Brain

Experience-dependent changes in synaptic connectivity are thought to play a vital role not only in memory formation, but also in long-term adaptive responses involved in mood regulation, reward behavior, and pain control. The neurotrophin, brain-derived neurotrophic factor (BDNF), which has recently been implicated in memory formation and aspects of major depression, is also an important regulator of long-term synaptic plasticity in the adult mammalian brain. We have investigated BDNF function in the dentate gyrus, a brain region implicated in depression and the action of antidepressant drugs. Local infusion of BDNF into the dentate gyrus generated a long-term potentiation (LTP) of synaptic efficacy at medial perforant path-granule cell synapses. This LTP is associated with expression of the immediate early gene, Arc, in postsynaptic granule cells and transport of Arc mRNA to synaptic regions on dendrites. Using local infusion of antisense oligodeoxynucleotides to block Arc synthesis, we show that Arc is required for the induction and time-dependent consolidation of BDNF-induced LTP. The sustained synthesis of Arc during a critical time-window is required for local expansion of the actin cytoskeletal network in dendritic spines. These results identify Arc as a critical mediator of BDNF in long-term synaptic plasticity in the adult brain. Microarray expression profiling has further revealed a panel of genes that, like Arc, are strongly upregulated following acute BDNF infusion or chronic treatment with the antidepressant fluoxetine.

P42/44 MAP Kinase Inhibitor PD98059 Attenuates Multiple Forms of Synaptic Plasticity in Rat Dentate Gyrus In Vitro

1999 ◽  
Vol 81 (1) ◽  
pp. 103-110 ◽  
Author(s):  
Andrew N. Coogan ◽  
Deirdre M. O'Leary ◽  
John J. O'Connor
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Map Kinase ◽  
Channel Blocker ◽  
Kinase Inhibitor ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Multiple Forms

Coogan, Andrew N., Deirdre M. O'Leary, and John J. O'Connor. P42/44 MAP kinase inhibitor PD98059 attenuates multiple forms of synaptic plasticity in rat dentate gyrus in vitro. J. Neurophysiol. 81: 103–110, 1999. The effects of the specific p42/44 mitogen-activated protein (MAP) kinase cascade inhibitor, PD98059, were investigated on three types of long-term potentiation (LTP) in the medial perforant path of the rat dentate gyrus in vitro: LTP induced by 1) high-frequency stimulation (HFS-LTP), 2) application for 10 min of the K+ channel blocker, tetraethylammonium chloride (TEA-LTP), and 3) application of the metabotropic glutamate receptor (mGluR) agonist (S)-dihydrophenylglycine (S-DHPG) for 2 min (DHPG-LTP). Bath perfusion of PD98059 (50 μM) for 1 h inhibited HFS-LTP (111 ± 5%, mean ± SE, at 90 min posttetanus in test slices compared with 144 ± 5% in control slices; n = 6–7). Concentrations of 10 and 20 μM PD98059 had no effect on HFS-LTP ( n = 6). PD98059 (50 μM) had no effect on the isolated N-methyl-d-aspartate excitatory postsynaptic potential (NMDA-EPSP) or on the maintenance phase of HFS-LTP. PD98059 (50 μM) did not affect paired-pulse depression (PPD; interstimulus intervals of 10 and 100 ms) of synaptic transmission as is typically observed in the medial perforant path of the dentate gyrus. Bath application of (S)-DHPG (40 μM) for 2 min gave rise to a potentiation of the EPSPs slope (148 ± 4% at 1 h post-DHPG wash out; n = 5). Pretreatment of slices with PD98059 (50 μM) inhibited the DHPG-LTP (98 ± 3% at 1 h post-DHPG wash out; n = 5). The TEA-LTP (125 ± 4% at 1 h post-TEA wash out; n = 6) was found to be both d-2-amino-5-phosphonopentanoic acid (d-AP5; 100 μM) and nifedipine (20 μM) independent. However, the T type voltage-dependent calcium-channel blocker, NiCl2 (50 μM), completely inhibited the observed potentiation. The mGluR receptor antagonist α-methyl-4-carboxy-phenyl glycine (MCPG; 100 μM) and PD98059 (50 μM) caused a complete block of the TEA-LTP. These data show for the first time an involvement of the p42/44 MAP kinase in the induction and expression of both an NMDA-dependent and two forms of NMDA-independent LTP in the dentate gyrus.

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