Effect of destruction of dentate granule cells on kindling induced by stimulation of the perforant path

1993 ◽  
Vol 53 (1) ◽  
pp. 45-49 ◽  
Author(s):  
Clifford L. Mitchell ◽  
Martha I. Barnes
Keyword(s):  
Granule Cells ◽  
Perforant Path ◽  
Dentate Granule Cells ◽  
Stimulation Of

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

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.

Shunting of excitatory input to dentate gyrus granule cells by a depolarizing GABAA receptor-mediated postsynaptic conductance

1992 ◽  
Vol 68 (1) ◽  
pp. 197-212 ◽  
Author(s):  
K. J. Staley ◽  
I. Mody
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Ampa Receptor ◽  
Time Constant ◽  
Granule Cell ◽  
Granule Cells ◽  
Reversal Potential ◽  
Perforant Path ◽  
Stimulation Of

1. Stimulation of the perforant path in the outer molecular layer of the adult rat dentate gyrus produced a depolarizing post-synaptic potential (DPSP) in granule cells when recorded using whole-cell techniques in the standard hippocampal slice preparation at 34 degrees C. The postsynaptic currents (PSCs) contributing to the DPSP were analyzed using specific receptor antagonists in current- and voltage-clamp recordings. 2. The DPSP reversal potential was dependent on the intracellular chloride concentration, and the amplitude of the DPSP was increased 55% after perfusion of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline methiodide (BMI). The GABAA receptor-mediated PSC reversed at -66 mV, which was 19 mV positive to the resting membrane potential (-85 mV) but hyperpolarized relative to action potential threshold. At -35 mV, the GABAA PSC had a latency to peak of 12.9 ms after the stimulus and decayed monoexponentially with an average time constant of 23.4 ms. 3. The component of the PSC blocked by the Quis/AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) had a latency to peak of 7.1 ms and decayed monoexponentially with a time constant of 9.9 ms at -35 mV. The N-methyl-D-aspartate (NMDA) receptor-mediated PSC, which was blocked by D-amino-5-phosphonovaleric acid (D-AP5), had a waveform that was similar to the GABAA PSC: the latency to peak was 16 ms and the decay was monoexponential with a time constant of 24.5 ms at -35 mV. 4. The ratio of the peak PSCs mediated by GABAA, Quis/AMPA, and NMDA receptors measured at -35 mV with cesium gluconate electrode solutions was 1:0.2:0.1. This ratio was essentially constant over the range of stimulus intensities that produced compound PSC amplitudes of 80-400 pA. 5. Measured at its reversal potential, the GABAA receptor-mediated postsynaptic conductance (GGABA-A) decreased the peak DPSP amplitude by 35%, shunted 50% of the charge transferred to the soma by the excitatory PSC, and completely inhibited the NMDA receptor-mediated component of the DPSP. 6. Simultaneous stimulation of presynaptic fibers from both the perforant path and interneurons results in a large depolarizing GGABA-A that inhibits the granule cell by shunting the excitatory PSCs. As predicted by models of shunting, the similar kinetics of the GABAA and NMDA PSCs leads to particularly effective inhibition of the NMDA PSC. The more rapid Quis/AMPA PSC is less affected by the GGABA-A, so that granule cell excitation under these conditions is primarily due to Quis/AMPA receptor activation.

Epileptogenesis Is Associated With Enhanced Glutamatergic Transmission in the Perforant Path

2006 ◽  
Vol 95 (2) ◽  
pp. 1213-1220 ◽  
Author(s):  
Annalisa Scimemi ◽  
Stephanie Schorge ◽  
Dimitri M. Kullmann ◽  
Matthew C. Walker
Keyword(s):  
Status Epilepticus ◽  
Nmda Receptor ◽  
Temporal Lobe ◽  
Cross Talk ◽  
Granule Cells ◽  
Perforant Path ◽  
Seizure Threshold ◽  
Glutamatergic Transmission ◽  
Dentate Granule Cells ◽  
Receptor Kinetics

The perforant path provides the main excitatory input into the hippocampus and has been proposed to play a critical role in the generation of temporal lobe seizures. It has been hypothesized that changes in glutamatergic transmission in this pathway promote the epileptogenic process and seizure generation. We therefore asked whether epileptogenesis is associated with enhanced glutamatergic transmission from the perforant path to dentate granule cells. We used a rat model of temporal lobe epilepsy in which spontaneous seizures occur after an episode of pilocarpine-induced status epilepticus. Whole cell patch-clamp recordings were obtained from dentate granule cells in hippocampal slices from control and epileptic animals 3 wk after pilocarpine-induced status epilepticus. The paired pulse ratio of perforant path-evoked AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) was reduced in tissue obtained from epileptic rats. This is consistent with an increase in release probability. N-methyl-d-aspartate (NMDA) receptor-mediated EPSCs were also prolonged. This prolongation could not be accounted for by decreased activity of glutamate transporters or by a change in NMDA receptor subunit composition in dentate granule cells, implying a change in NMDA receptor kinetics. This change in NMDA receptor kinetics was associated with the emergence of significant synaptic cross-talk, detected as a use-dependent block of receptors activated by medial perforant path synapses after lateral perforant path stimulation in MK-801. Enhanced glutamatergic transmission and the emergence of cross-talk among perforant path-dentate granule cell synapses may contribute to lowering seizure threshold.

Activity of dentate granule cells during learning: Differentiation of perforant path input

1979 ◽  
Vol 169 (1) ◽  
pp. 29-43 ◽  
Author(s):  
Sam A. Deadwyler ◽  
Mark West ◽  
Gary Lynch
Keyword(s):  
Granule Cells ◽  
Perforant Path ◽  
Dentate Granule Cells

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.

scholarly journals Blockade of excitation reveals inhibition of dentate spiny hilar neurons recorded in rat hippocampal slices

1992 ◽  
Vol 68 (3) ◽  
pp. 978-984 ◽  
Author(s):  
H. E. Scharfman
Keyword(s):  
Granule Cells ◽  
Excitatory Amino Acid ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Perforant Path ◽  
Mossy Cells ◽  
Amino Acid Antagonists ◽  
Hilar Neurons ◽  
Local Circuitry ◽  
Stimulation Of

1. Extracellular and intracellular recordings in rat hippocampal slices were used to compare the synaptic responses to perforant path stimulation of granule cells of the dentate gyrus, spiny “mossy” cells of the hilus, and area CA3c pyramidal cells of hippocampus. Specifically, we asked whether aspects of the local circuitry could explain the relative vulnerability of spiny hilar neurons to various insults to the hippocampus. 2. Spiny hilar cells demonstrated a surprising lack of inhibition after perforant path activation, despite robust paired-pulse inhibition and inhibitory postsynaptic potentials (IPSPs) in adjacent granule cells and area CA3c pyramidal cells in response to the same stimulus in the same slice. However, when the slice was perfused with excitatory amino acid antagonists [6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), or CNQX with 2-amino-5-phosphonovaleric acid (APV)], IPSPs could be observed in spiny hilar cells in response to perforant path stimulation. 3. The IPSPs evoked in spiny hilar cells in the presence of CNQX were similar in their reversal potentials and bicuculline sensitivity to IPSPs recorded in dentate granule cells or hippocampal pyramidal cells in the absence of CNQX. 4. These results demonstrate that, at least in slices, perforant path stimulation of spiny hilar cells is primarily excitatory and, when excitation is blocked, underlying inhibition can be revealed. This contrasts to the situation for dentate and hippocampal principal cells, which are ordinarily dominated by inhibition, and only when inhibition is compromised can the full extent of excitation be appreciated.(ABSTRACT TRUNCATED AT 250 WORDS)

Decrement of GABAA receptor-mediated inhibitory postsynaptic currents in dentate granule cells in epileptic hippocampus

1996 ◽  
Vol 75 (5) ◽  
pp. 1901-1908 ◽  
Author(s):  
M. Isokawa
Keyword(s):  
Nmda Receptor ◽  
Granule Cells ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Patch Clamp Recording ◽  
Dentate Granule Cells ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Pilocarpine Model ◽  
Frequency Stimulation

1. Inhibitory postsynaptic currents (IPSCs) were studied in hippocampal dentate granule cells (DGCs) in the pilocarpine model and human temporal lobe epilepsy, with the use of the whole cell patch-clamp recording technique in slice preparations. 2. In the pilocarpine model, hippocampal slices were prepared from rats that were allowed to experience spontaneous seizures for 2 mo. Human hippocampal specimens were obtained from epileptic patients who underwent surgical treatment for medically intractable seizures. 3. IPSCs were generated by single perforant path stimulation and recorded at a membrane potential (Vm) of 0 mV near the reversal potential of glutamate excitatory postsynaptic currents in the voltage-clamp recording. IPSCs were pharmacologically identified as gamma-aminobutyric acid-A (GABAA) IPSCs by 10 microM bicuculline methiodide. 4. During low-frequency stimulation, IPSCs were not different in amplitude among non-seizure-experienced rat hippocampi, human nonsclerotic hippocampi, seizure-experienced rat hippocampi, and human sclerotic hippocampi. In the last two groups of DGCs, current-clamp recordings indicated the presence of prolonged excitatory postsynaptic potentials (EPSPs) mediated by the N-methyl-D-aspartate (NMDA) receptor. 5. High-frequency stimulation, administered at Vm = -30 mV to activate NMDA currents, reduced GABAA IPSC amplitude specifically in seizure-experienced rat hippocampi (t = 2.5, P < 0.03) and human sclerotic hippocampi (t = 7.7, P < 0.01). This reduction was blocked by an NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV) (50 microM). The time for GABAA IPSCs to recover to their original amplitude was also shortened by the application of APV. 6. I conclude that, when intensively activated, NMDA receptor-mediated excitatory transmission may interact with GABAergic synaptic inhibition in DGCs in seizure-experienced hippocampus to transiently reduce GABA(A) receptor-channel function. Such interactions may contribute to give rise to epileptic excitation in chronically seizure-prone hippocampus.

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