PKA and PKC Enhance Excitatory Synaptic Transmission in Human Dentate Gyrus

2003 ◽  
Vol 89 (5) ◽  
pp. 2482-2488 ◽  
Author(s):  
Huan-Xin Chen ◽  
Steven N. Roper
Keyword(s):  
Protein Kinase ◽  
Synaptic Transmission ◽  
Dentate Gyrus ◽  
Phorbol Ester ◽  
Granule Cells ◽  
Excitatory Synaptic Transmission ◽  
Perforant Path ◽  
Short Term ◽  
Dentate Granule Cells ◽  
Presynaptic Mechanisms

cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) are two major modulators of synaptic transmission in the CNS but little is known about how they affect synaptic transmission in the human CNS. In this study, we used forskolin, a PKA activator, and phorbol ester, a PKC activator, to examine the effects of these kinases on synaptic transmission in granule cells of the dentate gyrus in human hippocampal slices using whole-cell recording methods. We found that both forskolin and phorbol ester increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) but left the amplitude unaffected. Inactive forskolin and phorbol ester had no effect on sEPSCs in human dentate granule cells. Prior application of forskolin occluded the effects of phorbol ester on mEPSC frequency. Tetanic stimulation applied to the perforant path induced short-term depression in dentate gyrus granule cells. Both forskolin and phorbol ester significantly enhanced this short-term depression. Taken together, these results demonstrate that PKA and PKC are involved in up-regulation of excitatory synaptic transmission in human dentate granule cells, primarily by presynaptic mechanisms. In addition, the occlusion experiments suggest that the two kinases may share a common signal pathway.

Cancer Metastasis–Suppressing Peptide Metastin Upregulates Excitatory Synaptic Transmission in Hippocampal Dentate Granule Cells

2005 ◽  
Vol 94 (5) ◽  
pp. 3648-3652 ◽  
Author(s):  
Amy C. Arai ◽  
Yan-Fang Xia ◽  
Erika Suzuki ◽  
Markus Kessler ◽  
Olivier Civelli ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Dentate Gyrus ◽  
G Protein ◽  
Tyrosine Kinases ◽  
Map Kinases ◽  
Cancer Metastasis ◽  
Granule Cells ◽  
Excitatory Synaptic Transmission ◽  
Dependent Manner ◽  
Dentate Granule Cells

Metastin is an antimetastatic peptide encoded by the KiSS-1 gene in cancer cells. Recent studies found that metastin is a ligand for the orphan G-protein–coupled receptor GPR54, which is highly expressed in specific brain regions such as the hypothalamus and parts of the hippocampus. This study shows that activation of GPR54 by submicromolar concentrations of metastin reversibly enhances excitatory synaptic transmission in hippocampal dentate granule cells in a mitogen-activated protein (MAP) kinase–dependent manner. Synaptic enhancement by metastin was suppressed by intracellular application of the G-protein inhibitor GDP-β-S and the calcium chelator BAPTA. Analysis of miniature excitatory postsynaptic currents (mEPSCs) revealed an increase in the mean amplitude but no change in event frequency. This indicates that GPR54 and the mechanism responsible for the increase in EPSCs are postsynaptic. Metastin-induced synaptic potentiation was abolished by 50 μM PD98059 and 20 μM U0126, two inhibitors of the MAP kinases ERK1 and ERK2. The effect was also blocked by inhibitors of calcium/calmodulin-dependent kinases and tyrosine kinases. RT-PCR experiments showed that both KiSS-1 and GPR54 are expressed in the hippocampal dentate gyrus. Metastin is thus a novel endogenous factor that modulates synaptic excitability in the dentate gyrus through mechanisms involving MAP kinases, which in turn may be controlled upstream by calcium-activated kinases and tyrosine kinases.

scholarly journals Acute Intrahippocampal Infusion of BDNF Induces Lasting Potentiation of Synaptic Transmission in the Rat Dentate Gyrus

1998 ◽  
Vol 79 (1) ◽  
pp. 496-499 ◽  
Author(s):  
Elhoucine Messaoudi ◽  
Kjetil Bårdsen ◽  
Bolek Srebro ◽  
Clive R. Bramham
Keyword(s):  
Synaptic Transmission ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Molecular Layer ◽  
Epileptiform Activity ◽  
Population Spike ◽  
Perforant Path ◽  
Excitatory Postsynaptic Potential ◽  
Adult Rats ◽  
Fepsp Slope

Messaoudi, Elhoucine, Kjetil Bårdsen, Bolek Srebro, and Clive R. Bramham. Acute intrahippocampal infusion of BDNF induces lasting potentiation of synaptic transmission in the rat dentategyrus. J. Neurophysiol. 79: 496–499, 1998. The effect of acuteintrahippocampal infusion of brain-derived neurotrophic factor (BDNF) on synaptic transmission in the dentate gyrus was investigated in urethan-anesthetized rats. Medial perforant path-evoked field potentials were recorded in the dentate hilus and BDNF-containing buffer was infused (4 μl, 25 min) immediately above the dentate molecular layer. BDNF led to a slowly developing increase of the field excitatory postsynaptic potential (fEPSP) slope and population spike amplitude. The potentiation either reached a plateau level at ∼2 h after BDNF infusion or continued to increase for the duration of experiment; the longest time point recorded was 10 h. Mean increases at 4 h after BDNF infusion were 62.2 and 224% for the fEPSP slope and population spike, respectively. No changes in responses were observed in controls receiving buffer medium only or buffer containing cytochrome C. BDNF-induced potentiation developed in the absence of epileptiform activity in the hippocampal electroencephalogram or changes in recurrent inhibition on granule cells as assessed by paired-pulse inhibition of the population spike. We conclude that exogenous BDNF induces a lasting potentiation of synaptic efficacy in the dentate gyrus of anesthetized adult rats.

Effect of Chronic Stress on Synaptic Currents in Rat Hippocampal Dentate Gyrus Neurons

2003 ◽  
Vol 89 (1) ◽  
pp. 625-633 ◽  
Author(s):  
Henk Karst ◽  
Marian Joëls
Keyword(s):  
Dentate Gyrus ◽  
Chronic Stress ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Perforant Path ◽  
Maximal Response ◽  
Stress Exposure ◽  
Dentate Granule Cells ◽  
Prior Stress ◽  
Synaptic Responses

We investigated the effect of chronic stress on synaptic responses of rat dentate granule cells to perforant path stimulation. Rats were subjected for 3 wk to unpredictable stressors twice daily or to control handling. One day after the last stressor, hippocampal slices were prepared and synaptic responses were determined with whole-cell recording. At that time, adrenal weight was found to be increased and thymus weight as well as gain in body weight were decreased in the stressed versus control animals, indicative of corticosterone hypersecretion during the stress period. In slices from rats with basal corticosteroid levels (at the circadian trough, under rest), no effect of prior stress exposure was observed on synaptic responses. However, synaptic responses of dentate granule cells from chronically stressed and control rats were differently affected by in vitro activation of glucocorticoid receptors, i.e., 1–4 h after administration of 100 nM corticosterone for 20 min. Thus the maximal response to synaptic activation of dentate cells at holding potential of −70 mV [when N-methyl-d-aspartate (NMDA) receptors are blocked by magnesium] was significantly enhanced after corticosterone administration in chronically stressed but not in control animals. In accordance, the amplitude of α-amino-3-hydroxy-5-methylisolazole-4-propionic acid (AMPA) but not of NMDA receptor-mediated currents was increased by corticosterone in stressed rats, over the entire voltage range. Corticosterone treatment also decreased the time to peak of AMPA currents, but this effect did not depend on prior stress exposure. The data indicate that following chronic stress exposure synaptic excitation of dentate granule cells may be enhanced when corticosterone levels rise. This enhanced synaptic flow could contribute to enhanced excitation of projection areas of the dentate gyrus, most notably the CA3 hippocampal region.

Orphanin FQ/Nociceptin Inhibits Synaptic Transmission and Long-Term Potentiation in Rat Dentate Gyrus Through Postsynaptic Mechanisms

1998 ◽  
Vol 80 (3) ◽  
pp. 1277-1284 ◽  
Author(s):  
Tzu-Ping Yu ◽  
Cui-Wei Xie
Keyword(s):  
Synaptic Transmission ◽  
Dentate Gyrus ◽  
Nmda Receptors ◽  
Opioid Receptor ◽  
Granule Cells ◽  
Long Term Potentiation ◽  
Orphanin Fq ◽  
Dentate Granule Cells ◽  
Term Potentiation

Yu, Tzu-Ping and Cui-Wei Xie. Orphanin FQ/nociceptin inhibits synaptic transmission and long-term potentiation in the rat dentate gyrus through postsynaptic mechanisms. J. Neurophysiol. 80: 1277–1284, 1998. Orphanin FQ/nociceptin (OFQ), a recently characterized natural ligand for the opioid receptor-like 1 (ORL1) receptor, shares structural similarity to the endogenous opioids. Our previous study found that OFQ, like classical opioids, modulated synaptic transmission and long-term potentiation (LTP) in the hippocampal CA1 region, suggesting a modulatory role for OFQ in synaptic plasticity involved in learning and memory. In the present study we investigated the action of OFQ in the dentate gyrus and explored possible underlying cellular mechanisms. Field potential recordings showed that OFQ significantly inhibited excitatory synaptic transmission and LTP induction in the dentate lateral perforant path. In the presence of OFQ, the excitatory postsynaptic potential (EPSP) slope-population spike (E-S) curve was shifted to the right, and no significant change was found in paired-pulse facilitation, suggesting a postsynaptic mechanism responsible for the inhibition of synaptic transmission. Under whole cell voltage-clamp conditions, bath application of OFQ activated K+ currents in most granule cells tested at a holding potential of −50 mV, suggesting that OFQ could reduce the excitability of dentate granule cells by hyperpolarizing cell membranes. OFQ also inhibited the amplitude of N-methyl-d-aspartate (NMDA) receptor–mediated excitatory postsynaptic currents (EPSCs) without affecting α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor–mediated EPSCs. This inhibition was not blocked by opioid receptor antagonists. Furthermore, the inward currents evoked by focal application of NMDA to granule cells were suppressed by OFQ in a dose-dependent manner, suggesting that OFQ may suppress LTP by inhibiting the function of postsynaptic NMDA receptors. These results demonstrate that OFQ may negatively modulate synaptic transmission and plasticity in the dentate gyrus through postsynaptic mechanisms, including hyperpolarization of granule cells as well as inhibition of the function of postsynaptic NMDA receptors/channels in dentate granule cells.

scholarly journals Serotonin modulates the excitatory synaptic transmission in the dentate granule cells

2016 ◽  
Vol 115 (6) ◽  
pp. 2997-3007 ◽  
Author(s):  
Kanako Nozaki ◽  
Reika Kubo ◽  
Yasuo Furukawa
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Hippocampal Formation ◽  
Membrane Resistance ◽  
Perforant Path ◽  
Excitatory Synapses ◽  
Dentate Granule Cells ◽  
Pulse Ratio ◽  
Mossy Cell ◽  
Stimulation Of

Serotonergic fibers from the raphe nuclei project to the hippocampal formation, the activity of which is known to modulate the inhibitory interneurons in the dentate gyrus. On the other hand, serotonergic modulation of the excitatory synapses in the dentate gyrus is not well examined. In the present study, we examined the effects of 5-HT on the excitatory postsynaptic potentials (EPSPs) in the dentate granule cells evoked by the selective stimulation of the lateral perforant path (LPP), the medial perforant path (MPP), or the mossy cell fibers (MCF). 5-HT depressed the amplitude of unitary EPSPs (uEPSPs) evoked by the stimulation of LPP or MPP, whereas uEPSPs evoked by MCF stimulation were little affected. The effect was partly explained by the decrease of the resting membrane resistance following the activation of 5-HT1A receptors, which was confirmed by computer simulations. We also found that the probability of evoking uEPSP by LPP stimulation but not MPP or MCF stimulation was reduced by 5-HT and that the paired-pulse ratio of LPP-evoked EPSP but not that of MPP- or MCF-evoked ones was increased by 5-HT. These effects were blocked by 5-HT2 antagonist, suggesting that the transmitter release in the LPP-granule cell synapse is inhibited by the activation of 5-HT2 receptors. The present results suggest that 5-HT can modulate the EPSPs in the dentate granule cells by at least two distinct mechanisms

scholarly journals Effect of Adrenalectomy on Membrane Properties and Synaptic Potentials in Rat Dentate Granule Cells

2001 ◽  
Vol 85 (2) ◽  
pp. 699-707 ◽  
Author(s):  
M. Joëls ◽  
C. Stienstra ◽  
Y. Karten
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Cell Loss ◽  
Perforant Path ◽  
Membrane Properties ◽  
Similar Extent ◽  
Dentate Granule Cells ◽  
Field Response ◽  
Induced Changes ◽  
Synaptic Responses

Adrenalectomy is known to accelerate both neurogenesis and cell death of granule cells located in the suprapyramidal blade of the rat dentate gyrus. Three days after adrenalectomy, some granule cells have already died by apoptosis while newly formed cells are not yet incorporated in the cell layer, resulting in a temporary loss of granule cells. Concomitantly, the field response to stimulation of perforant path afferents is reduced. While the temporary cell loss is likely to attenuate synaptic field responses, adrenalectomy-induced changes in properties of the surviving cells may also contribute to the reduction in field response amplitude. To address this possibility, we here investigated the membrane properties and synaptic responses of dentate granule cells, 3 days after adrenalectomy. We found that passive and most of the active membrane properties of granule cells in adrenalectomized rats were not significantly different from the cell properties in sham-operated controls. However, intracellularly recorded synaptic responses from surviving granule cells were markedly reduced after adrenalectomy. The N-methyl-d-aspartate (NMDA)– and the non-NMDA receptor–mediated components were reduced to a similar extent, suggesting that the attenuation of synaptic transmission after adrenalectomy could be partly of presynaptic origin. The data indicate that the earlier observed attenuation of synaptic field responses after adrenalectomy may be partly due to a diminished glutamatergic input to the dentate gyrus and not exclusively to a loss of granule cells participating in the synaptic circuit.

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