The action of some analogues of the excitatory amino acids in the dentate gyrus of the rat

1984 ◽  
Vol 62 (4) ◽  
pp. 424-429 ◽  
Author(s):  
G. L. Collingridge ◽  
S. J. Kehl ◽  
H. McLennan
Keyword(s):  
Amino Acids ◽  
Dentate Gyrus ◽  
Nmda Receptors ◽  
Aspartic Acid ◽  
Excitatory Amino Acids ◽  
Granule Cells ◽  
Nmda Antagonist ◽  
Dentate Granule Cells

We have confirmed that γ-D-glutamylglycine and the L-isomer of 2-amino-4-phosphonobutyric acid, and have shown also that L-2-amino-5-phosphonovaleric (L-APV) acid, are antagonists of synaptic excitations of dentate granule cells induced from both lateral and medial perforant paths. The N-methyl-D-aspartic acid (NMDA) antagonist D-APV is without effect. The synaptic antagonists reduce the presynaptic fibre volley particularly in the lateral path, suggesting that a reduced transmitter output contributes to their action. NMDA receptors exist upon the granule cells, but they are not involved with these synaptic processes.

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 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.

The chemokine SDF1 regulates migration of dentate granule cells

Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4249-4260 ◽  
Author(s):  
Anil Bagri ◽  
Theresa Gurney ◽  
Xiaoping He ◽  
Yong-Rui Zou ◽  
Dan R. Littman ◽  
...  
Keyword(s):  
Cell Migration ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Granule Cells ◽  
Ectopic Expression ◽  
Dentate Granule Cell ◽  
Vitro Assay ◽  
Dentate Granule Cells ◽  
Cell Position

The dentate gyrus is the primary afferent pathway into the hippocampus, but there is little information concerning the molecular influences that govern its formation. In particular, the control of migration and cell positioning of dentate granule cells is not clear. We have characterized more fully the timing and route of granule cell migration during embryogenesis using in utero retroviral injections. Using this information, we developed an in vitro assay that faithfully recapitulates important events in dentate gyrus morphogenesis. In searching for candidate ligands that may regulate dentate granule cell migration, we found that SDF1, a chemokine that regulates cerebellar and leukocyte migration, and its receptor CXCR4 are expressed in patterns that suggest a role in dentate granule cell migration. Furthermore, CXCR4 mutant mice have a defect in granule cell position. Ectopic expression of SDF1 in our explant assay showed that it directly regulates dentate granule cell migration. Our study shows that a chemokine is necessary for the normal development of the dentate gyrus, a forebrain structure crucial for learning and memory.

scholarly journals Biochemical Markers of Excitability in Human Neocortex

1991 ◽  
Vol 18 (S4) ◽  
pp. 640-644 ◽  
Author(s):  
A.L. Sherwin ◽  
O. Vernet ◽  
F. Dubeau ◽  
A. Olivier
Keyword(s):  
Amino Acids ◽  
Tyrosine Hydroxylase ◽  
Glutamic Acid ◽  
Aspartic Acid ◽  
Biochemical Markers ◽  
Excitatory Amino Acids ◽  
Inhibitory Neurotransmitters ◽  
Catecholamine Biosynthesis ◽  
Interictal Spike ◽  
Inhibitory Mechanisms

ABSTRACT:We measured biochemical markers of excitability in brain excised for neurosurgical therapy of epilepsy. Intraoperative electrocorticography was used to identify and compare samples from regions of persistent interictal spike discharges and areas of the cerebral convexity which were free of interictal piking. We found that interictal spiking was associated with elevated tissue levels of the excitatory amino acids glutamic acid (26%, p < 0.001) and aspartic acid (25%, p < 0.05). There was also a significant increase in the activity of the enzymes glutamic acid dehydrogenase (20%, p < 0.01) and aspartate acid aminotransferase (18%, p < 0.01) which are involved in their formation. There was no change in the levels of the inhibitory neurotransmitters GABA or taurine. We also found a significant increase in the activity of tyrosine hydroxylase (52%, p < 0.001), the rate controlling enzyme in catecholamine biosynthesis. There was a reduction in the density (Bmax) of cortical alpha-1 adrenoceptors (26%, p < 0.01) and a concommitant diminution of receptor coupled phosphatidylinositide metabolism (21%, p < 0.01). This blunting of inhibitory noradrenergic transmembrane signaling may contribute to a relative imbalance between excitatory and inhibitory mechanisms in epileptogenic neocortex.

scholarly journals Does a Unique Type of CA3 Pyramidal Cell in Primates Bypass the Dentate Gate?

2005 ◽  
Vol 94 (1) ◽  
pp. 896-900 ◽  
Author(s):  
Paul S. Buckmaster
Keyword(s):  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Synaptic Input ◽  
Granule Cells ◽  
Molecular Layer ◽  
Pyramidal Cells ◽  
Dendritic Morphology ◽  
Dentate Granule Cells ◽  
Excitatory Synaptic Input ◽  
Ca3 Pyramidal Cells

The predominant excitatory synaptic input to the hippocampus arises from entorhinal cortical axons that synapse with dentate granule cells, which in turn synapse with CA3 pyramidal cells.Thus two highly excitable brain areas—the entorhinal cortex and the CA3 field—are separated by dentate granule cells, which have been proposed to function as a gate or filter. However, unlike rats, primates have “dentate” CA3 pyramidal cells with an apical dendrite that extends into the molecular layer of the dentate gyrus, where they could receive strong, monosynaptic, excitatory synaptic input from the entorhinal cortex. To test this possibility, the dentate gyrus molecular layer was stimulated while intracellular recordings were obtained from CA3 pyramidal cells in hippocampal slices from neurologically normal macaque monkeys. Stimulus intensity of the outer molecular layer of the dentate gyrus was standardized by the threshold intensity for evoking a dentate gyrus field potential population spike. Recorded proximal CA3 pyramidal cells were labeled with biocytin, processed with diaminobenzidine for visualization, and classified according to their dendritic morphology. In response to stimulation of the dentate gyrus molecular layer, action potential thresholds were similar in proximal CA3 pyramidal cells with different dendritic morphologies. These findings do not support the hypothesis that dentate CA3 pyramidal cells receive stronger synaptic input from the entorhinal cortex than do other proximal CA3 pyramidal cells.

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