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.

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 Bilateral Agenesis of the Hippocampal Dentate Gyrus in a Neurologically Normal Adult

2006 ◽  
Vol 33 (3) ◽  
pp. 296-301 ◽  
Author(s):  
Arthur W. Clark ◽  
Harvey B. Sarnat
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Hippocampal Formation ◽  
Adult Life ◽  
Neurological Deficits ◽  
Null Mouse ◽  
Hippocampal Dentate Gyrus ◽  
Dentate Granule Cells ◽  
Neurodevelopmental Abnormalities ◽  
Neurologically Normal

ABSTRACT:Background:Ontogenic development of granule cells in the hippocampal dentate gyrus is influenced by genes including WNT3, EMX2, NEUROD, and LEF1. Dentate granule cells continue to be generated from stem cell precursors postnatally and during adult life, and are implicated in normal and abnormal neurological function. Developmental privation of dentate granule cells is rare and essentially always occurs in the context of other neurodevelopmental abnormalities. We have found no previous reports of severe, selective agenesis of dentate granule cells in humans.Methods:A gross and microscopic examination of the brain included appropriate histochemical and immunohistochemical preparations and examination of the hippocampal formation at multiple levels bilaterally.Results:This neurologically normal 82-year-old man was found to have bilateral agenesis of the hippocampal dentate gyrus, no identifiable dentate granule cells, and moderate disorganization of the pyramidal cell layer of Ammon's horn. We found no neurodevelopmental abnormalities outside the hippocampus.Conclusion:The hippocampal architectural alterations in this patient are similar to those associated with a murine Lef1 mutation, but our human case does not have the other congenital deficits reported in the Lef1-null mouse. Bilateral agenesis of the hippocampal dentate gyrus, and apparent failure of regeneration of dentate granule cells from stem cells in adult life, may occur without overt clinical neurological deficits.

Evidence for common expression mechanisms underlying heterosynaptic and associative long-term depression in the dentate gyrus

1995 ◽  
Vol 74 (3) ◽  
pp. 1244-1247 ◽  
Author(s):  
B. R. Christie ◽  
D. Stellwagen ◽  
W. C. Abraham
Keyword(s):  
Dentate Gyrus ◽  
High Frequency ◽  
Granule Cells ◽  
Perforant Path ◽  
Long Term Depression ◽  
Anesthetized Rats ◽  
Data Support ◽  
Activity Dependent ◽  
Stimulation Of

1. The extent to which heterosynaptic and prime-associative stimulation protocols generate different forms of long-term depression (LTD) was assessed in the lateral perforant path synapses terminating on dentate gyrus granule cells in pentobarbital-anesthetized rats. 2. Heterosynaptic LTD was induced in the lateral path by repeated tetanization of the medial path. Prime-associative LTD of the lateral path was induced by alternating high-frequency conditioning trains to the medial path and single shocks to the lateral path at 100-ms intervals, all occurring 10 min after priming stimulation of the lateral path (5 Hz, 80 pulses). 3. Induction of LTD by one administration of the prime-associative protocol was normally greater in magnitude than the LTD induced by the heterosynaptic protocol. Saturation of LTD by repeated delivery of the prime-associative protocol completely occluded the subsequent induction of LTD by the heterosynaptic protocol. Saturation of LTD by repeated delivery of the heterosynaptic protocol produced an 80% occlusion of the LTD generated by the prime-associative protocol. 4. These data support the hypothesis that activity-dependent (associative) and activity-independent (heterosynaptic) LTD involve overlapping expression mechanisms, despite having demonstrably different induction 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.

Amino acids and the synaptic pharmacology of granule cells in the dentate gyrus of the rat

1979 ◽  
Vol 57 (9) ◽  
pp. 973-978 ◽  
Author(s):  
T. P. Hicks ◽  
H. McLennan
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Granule Cells ◽  
Aminobutyric Acid ◽  
Perforant Path ◽  
Excitatory Effect ◽  
Anaesthetized Rats ◽  
Stimulation Of

Granule cells of the dentate gyrus in the hippocampi of anaesthetized rats were excited by stimulation of the contralateral hippocampus (the commissural input) and the ipsilateral entorhinal cortex (the perforant path). The cells were also activated by the electrophoretic administration of various amino acids. A selective antagonism of glutamate and perforant path excitations was obtained with glutamic acid diethylester, and of aspartate and other amino acid induced and commissural excitations with D- or DL-α-aminoadipate. An excitatory effect of α-aminoadipate which was sometimes observed was prevented by the γ-aminobutyric acid antagonist bicuculline, and may be a disinhibitory phenomenon. The results lend support to the proposition that the transmitter of the perforant path is glutamate while that of the commissural fibres is aspartate.

Increase in extracellular dopamine levels during clozapine-induced potentiation in the hippocampal dentate gyrus of chronically prepared rabbits

2008 ◽  
Vol 86 (5) ◽  
pp. 249-256 ◽  
Author(s):  
Takashi Kubota ◽  
Itsuki Jibiki ◽  
Akira Ishikawa ◽  
Tomomi Kawamura ◽  
Sonoko Kurokawa ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Nmda Receptor ◽  
Dentate Gyrus ◽  
Negative Symptoms ◽  
Clinical Effect ◽  
Perforant Path ◽  
Hippocampal Dentate Gyrus ◽  
Extracellular Dopamine ◽  
Stimulation Of ◽  
Synaptic Responses

We previously found that 20 mg/kg clozapine i.p. potentiated the excitatory synaptic responses elicited in the dentate gyrus by single electrical stimulation of the perforant path in chronically prepared rabbits. We called this phenomenon clozapine-induced potentiation and proved that it was an NMDA receptor-mediated event. This potentiation is presumably related to clozapine’s clinical effect on negative symptoms and cognitive dysfunctions in schizophrenia. In the present study, to investigate the mechanisms underlying clozapine-induced potentiation, we examined whether extracellular dopamine and 5-HT levels changed during the potentiation by using a microdialysis technique in the dentate gyrus. The extracellular concentrations of dopamine and 5-HT levels were measured every 5 min during all experiments. Extracellular 5-HT levels did not change, but dopamine levels eventually increased significantly during clozapine-induced potentiation. The increase in the dopamine levels occurred almost simultaneously with the induction of clozapine-induced potentiation. These results suggest that clozapine-induced potentiation is at least partly attributable to a dopamine-mediated potentiation of excitatory synaptic transmission. The present study implies that such phenomena occur also in the perforant path–dentate gyrus pathway.

scholarly journals Regionally Localized Recurrent Excitation in the Dentate Gyrus of a Cortical Contusion Model of Posttraumatic Epilepsy

2010 ◽  
Vol 103 (3) ◽  
pp. 1490-1500 ◽  
Author(s):  
Robert F. Hunt ◽  
Stephen W. Scheff ◽  
Bret N. Smith
Keyword(s):  
Head Injury ◽  
Dentate Gyrus ◽  
Action Potentials ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Granule Cell Layer ◽  
Mossy Fiber Sprouting ◽  
Posttraumatic Epilepsy ◽  
Dentate Granule Cells ◽  
Cortical Contusion

Posttraumatic epilepsy is a frequent consequence of brain trauma, but relatively little is known about how neuronal circuits are chronically altered after closed head injury. We examined whether local recurrent excitatory synaptic connections form between dentate granule cells in mice 8–12 wk after cortical contusion injury. Mice were monitored for behavioral seizures shortly after brain injury and ≤10 wk postinjury. Injury-induced seizures were observed in 15% of mice, and spontaneous seizures were observed weeks later in 40% of mice. Timm's staining revealed mossy fiber sprouting into the inner molecular layer of the dorsal dentate gyrus ipsilateral to the injury in 95% of mice but not contralateral to the injury or in uninjured controls. Whole cell patch-clamp recordings were made from granule cells in isolated hippocampal brain slices. Cells in slices with posttraumatic mossy fiber sprouting had an increased excitatory postsynaptic current (EPSC) frequency compared with cells in slices without sprouting from injured and control animals ( P < 0.001). When perfused with Mg2+-free artificial cerebrospinal fluid containing 100 μM picrotoxin, these cells had spontaneous bursts of EPSCs and action potentials. Focal glutamate photostimulation of the granule cell layer evoked a burst of EPSCs and action potentials indicative of recurrent excitatory connections in granule cells of slices with mossy fiber sprouting. In granule cells of slices without sprouting from injured animals and controls, spontaneous or photostimulation-evoked epileptiform activity was never observed. These results suggest that a new regionally localized excitatory network forms between dentate granule cells near the injury site within weeks after cortical contusion head injury.

scholarly journals Heterosynaptic NMDA Receptor Plasticity in Hippocampal Dentate Granule Cells

2022 ◽  
Author(s):  
Alma Rodenas-Ruano ◽  
Kaoutsar Nasrallah ◽  
Stefano Lutzu ◽  
Maryann Castillo ◽  
Pablo E. Castillo
Keyword(s):  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Information Transfer ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Dentate Granule Cells ◽  
Hippocampus Proper ◽  
Receptor Plasticity ◽  
Activity Dependent

The dentate gyrus is a key relay station that controls information transfer from the entorhinal cortex to the hippocampus proper. This process heavily relies on dendritic integration by dentate granule cells (GCs) of excitatory synaptic inputs from medial and lateral entorhinal cortex via medial and lateral perforant paths (MPP and LPP, respectively). N-methyl-D-aspartate receptors (NMDARs) can contribute significantly to the integrative properties of neurons. While early studies reported that excitatory inputs from entorhinal cortex onto GCs can undergo activity-dependent long-term plasticity of NMDAR-mediated transmission, the input-specificity of this plasticity along the dendritic axis remains unknown. Here, we examined the NMDAR plasticity rules at MPP-GC and LPP-GC synapses using physiologically relevant patterns of stimulation in acute rat hippocampal slices. We found that MPP-GC, but not LPP-GC synapses, expressed homosynaptic NMDAR-LTP. In addition, induction of NMDAR-LTP at MPP-GC synapses heterosynaptically potentiated distal LPP-GC NMDAR plasticity. The same stimulation protocol induced homosynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-LTP at MPP-GC but heterosynaptic AMPAR-LTD at distal LPP synapses, demonstrating that NMDAR and AMPAR are governed by different plasticity rules. Remarkably, heterosynaptic but not homosynaptic NMDAR-LTP required Ca2+ release from intracellular, ryanodine-dependent Ca2+ stores. Lastly, the induction and maintenance of both homo- and heterosynaptic NMDAR-LTP were blocked by GluN2D antagonism, suggesting the recruitment of GluN2D-containing receptors to the synapse. Our findings uncover a mechanism by which distinct inputs to the dentate gyrus may interact functionally and contribute to hippocampal-dependent memory formation.

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