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

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.

1970 ◽  
Vol 117 (3) ◽  
pp. 457-465 ◽  
Author(s):  
K. L. Manchester

1. The capacity of insulin to enhance the accumulation by muscle of several amino acids was studied. Reports that threonine uptake is enhanced by insulin were not confirmed, despite its enhanced incorporation into protein. Uptake of β-alanine and γ-aminobutyric acid also did not respond to the hormone. A stimulation of accumulation of alanine, histidine and ethionine was observed. 2. The capacity of inhibitors of protein synthesis to reveal a stimulation by insulin of accumulation of several amino acids, hitherto considered unresponsive to insulin in the absence of inhibitor, was confirmed. Cycloheximide was as effective as puromycin. However, two of these amino acids, alanine and histidine, here showed response to insulin in the absence of inhibitor. The presence of cycloheximide was found to enhance uptake of cycloleucine, ethionine and threonine; in its presence insulin enhanced uptake of β-alanine and α-methyltyrosine. 3. It is concluded that the influence of inhibitors of protein synthesis on amino acid accumulation and the response of amino acid accumulation to insulin are not adequately explained on the basis of inhibition of protein synthesis allowing amino acids to accumulate more readily. 4. The technical problems of whether linear rates of incorporation of amino acids into protein really indicate more than one cell pool are discussed and safeguards suggested. That initial rates of incorporation of label into protein are likely to be non-linear is shown.


1995 ◽  
Vol 74 (3) ◽  
pp. 1244-1247 ◽  
Author(s):  
B. R. Christie ◽  
D. Stellwagen ◽  
W. C. Abraham

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.


2016 ◽  
Vol 115 (6) ◽  
pp. 2997-3007 ◽  
Author(s):  
Kanako Nozaki ◽  
Reika Kubo ◽  
Yasuo Furukawa

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


1964 ◽  
Vol 11 (01) ◽  
pp. 064-074 ◽  
Author(s):  
Robert H Wagner ◽  
William D McLester ◽  
Marion Smith ◽  
K. M Brinkhous

Summary1. The use of several amino acids, glycine, alpha-aminobutyric acid, alanine, beta-alanine, and gamma-aminobutyric acid, as plasma protein precipitants is described.2. A specific procedure is detailed for the preparation of canine antihemophilic factor (AHF, Factor VIII) in which glycine, beta-alanine, and gammaaminobutyric acid serve as the protein precipitants.3. Preliminary results are reported for the precipitation of bovine and human AHF with amino acids.


2008 ◽  
Vol 86 (5) ◽  
pp. 249-256 ◽  
Author(s):  
Takashi Kubota ◽  
Itsuki Jibiki ◽  
Akira Ishikawa ◽  
Tomomi Kawamura ◽  
Sonoko Kurokawa ◽  
...  

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.


2022 ◽  
Author(s):  
Alma Rodenas-Ruano ◽  
Kaoutsar Nasrallah ◽  
Stefano Lutzu ◽  
Maryann Castillo ◽  
Pablo E. Castillo

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.


Author(s):  
A. Zavala ◽  
M. González ◽  
P. Pino

The objective of this research was to determine the quality of the protein present in sausages fortified with quinoa as a substitute for animal protein, through the identification and quantification of amino acids, using gas chromatography and precolumn derivatization. The amino acid composition found in the analyzed products was predominantly composed of: Threonine (THR) with a concentration of 1046.32µmol / L, aminobutyric acid (ABA) with a concentration of 9685.68 µmol / L and glutamic acid (GLU) with a concentration of 1178.71 µmol / L. These values were found in the treatment with the highest percentage of quinoa flour, establishing a directly proportional relationship between the concentrations of these amino acids and the percentage of quinoa. Gas chromatography was an adequate technique for determining the amino acid profile due to its speed and sensitivity. Keywords: amino acids, sausages, quinoa, derivatization, gas chromatography. RESUMEN La presente investigación tiene por objetivo determinar la calidad de la proteína presente en embutidos fortificados con quinua como sustituyente de la proteína animal, a través de la identificación y cuantificación de aminoácidos mediante la aplicación de cromatografía de gases y la derivatización precolumna. La composición de aminoácidos encontrada en los productos analizados destaca la presencia mayoritaria de: Treonina (THR) con una concentración de 1046,32 µmol/L, ácido aminobutírico (ABA) con una concentración de 9685,68 µmol/L  y ácido glutámico (GLU) con una concentración de 1178,71 µmol/L, todos estos valores se presentaron en el tratamiento con mayor porcentaje de harina de quinua estableciéndose una relación directamente proporcional entre las concentraciones de estos aminoácidos y el porcentaje de adición de quinua en los tratamientos estudiados. Se puede concluir que la cromatografía de gases empleada resultó una técnica adecuada para la determinación del perfil aminoacídico por la rapidez y sensibilidad presentada sobre las muestras estudiadas.  Palabras claves: aminoácidos, embutidos, quinua, derivatización, cromatografía de gases.  


1981 ◽  
Vol 36 (3-4) ◽  
pp. 310-318 ◽  
Author(s):  
J. Seredynski ◽  
T. Söylemez ◽  
W. Baumeister

Thin layers of synthetic homopolypeptides (poly-α-Ala, -Arg, -Asn, -Asp, -Glu, -His, -Lys and -Tyr) and proteins (myoglobin, concanavalin A, trypsin-inhibitor) were irradiated under solid state conditions in an electron microscope with 100 keV electrons. Radiolytic changes were investigated by amino acid analysis. The results are discussed in terms of the relative radiosensitivities of the constituent amino acids, and possible topochemical effects on the sensitivity pattern emerging. An attempt is also made to trace at least some of the predominant pathways of amino acid transformation, namely the production of alanine and a-aminobutyric acid


1999 ◽  
Vol 81 (2) ◽  
pp. 564-574 ◽  
Author(s):  
Ümit Sayin ◽  
Paul Rutecki ◽  
Thomas Sutula

NMDA-dependent currents in granule cells of the dentate gyrus contribute to induction but not permanence of kindling. Single-electrode voltage-clamp techniques and bath application of the N-methyl-d-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) were used to study the time course of seizure-induced alterations in NMDA-dependent synaptic currents in granule cells of the dentate gyrus in hippocampal slices from kindled and normal rats. In agreement with previous studies, granule cells from kindled rats examined within 1 wk after the last of 3 or 30–35 generalized tonic-clonic (class V) seizures demonstrated an increase in the NMDA receptor–dependent component of the perforant path–evoked synaptic current. Within 1 wk of the last kindled seizure, NMDA-dependent charge transfer underlying the perforant path–evoked current was increased by 63–111% at a holding potential of −30 mV. In contrast, the NMDA-dependent component of the perforant-evoked current in granule cells examined at 2.5–3 mo after the last of 3 or 90–120 class V seizures did not differ from age-matched controls. Because the seizure-induced increases in NMDA-dependent synaptic currents declined toward control values during a time course of 2.5–3 mo, increases in NMDA-dependent synaptic transmission cannot account for the permanent susceptibility to evoked and spontaneous seizures induced by kindling. The increase in NMDA receptor–dependent transmission was associated with the induction of kindling but was not responsible for the maintenance of the kindled state. The time course of alterations in NMDA-dependent synaptic current and the dependence of the progression of kindling and kindling-induced mossy fiber sprouting on repeated NMDA receptor activation are consistent with the possibility that the NMDA receptor is part of a transmembrane signaling pathway that induces long-term cellular alterations and circuit remodeling in response to repeated seizures, but is not required for permanent seizure susceptibility in circuitry altered by kindling.


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