Evidence for Endogenous Excitatory Amino Acids as Mediators in DSI of GABAAergic Transmission in Hippocampal CA1

1999 ◽  
Vol 82 (5) ◽  
pp. 2556-2564 ◽  
Author(s):  
Wade Morishita ◽  
Bradley E. Alger
Keyword(s):  
Amino Acids ◽  
Time Course ◽  
Metabotropic Glutamate Receptor ◽  
Excitatory Amino Acid ◽  
Pyramidal Cells ◽  
Kainate Receptors ◽  
Sulfinic Acid ◽  
Homocysteic Acid ◽  
Group I ◽  
Hippocampal Ca1

Depolarization-induced suppression of inhibition (DSI) is a process whereby brief ∼1-s depolarization to the postsynaptic membrane of hippocampal CA1 pyramidal cells results in a transient suppression of GABAAergic synaptic transmission. DSI is triggered by a postsynaptic rise in [Ca2+]in and yet is expressed presynaptically, which implies that a retrograde signal is involved. Recent evidence based on synthetic metabotropic glutamate receptor (mGluR) agonists and antagonists suggested that group I mGluRs take part in the expression of DSI and raised the possibility that glutamate or a glutamate-like substance is the retrograde messenger in hippocampal CA1. This hypothesis was tested, and it was found that the endogenous amino acidsl-glutamate (l-Glu) and l-cysteine sulfinic acid (l-CSA) suppressed GABAA-receptor–mediated inhibitory postsynaptic currents (IPSCs) and occluded DSI, whereas l-homocysteic acid (l-HCA) and l-homocysteine sulfinic acid (l-HCSA) did not. Activation of metabotropic kainate receptors with kainic acid (KA) reduced IPSCs; however, DSI was not occluded. When iontophoretically applied, both l-Glu andl-CSA produced a transient IPSC suppression similar in magnitude and time course to that observed during DSI. Both DSI and the actions of the amino acids were antagonized by (S)-α-methyl-4-carboxyphenylglycine ([S]-MCPG), indicating that the effects of the endogenous agonists were produced through activation of mGluRs. Blocking excitatory amino acid transport significantly increased DSI and the suppression produced by l-Glu orl-CSA without affecting the time constant of recovery from the suppression. Similar to DSI, IPSC suppression by l-Glu or l-CSA was blocked by N-ethylmaleimide (NEM). Moreover, paired-pulse depression (PPD), which is unaltered during DSI, is also not significantly affected by the amino acids. Taken together, these results support the glutamate hypothesis of DSI and argue that l-Glu or l-CSA are potential retrograde messengers in CA1.

A Fundamental Study of Quantitative Desulfurization of Sulfur Containing Amino Acids by Raney Nickel and its Character

1981 ◽  
Vol 36 (3) ◽  
pp. 370-374 ◽  
Author(s):  
Shinji Ohmori ◽  
Kazuko Takahashi ◽  
Mikiko Ikeda ◽  
Toshihiko Ubuka
Keyword(s):  
Amino Acids ◽  
Raney Nickel ◽  
Hydrogen Gas ◽  
Cysteic Acid ◽  
Sulfinic Acid ◽  
Fundamental Study ◽  
Homocysteic Acid ◽  
Ni Alloy ◽  
Ph Range ◽  
Sulfur Containing

Abstract The desulfurization of several naturally occurring sulfur-containing amino acids by Raney nickel was studied under various conditions. Raney nickel, which was prepared by treating Al-Ni alloy with 5 N NaOH at 60 °C for 30 min, and was not washed with water, was most active and desulfurized, in quantitative yield, methionine, homocysteine, homocystine, homocysteine sulfinic acid, S-(2-carboxy-n-propyl)-L-cysteine, cysteine, cystine, cysteine sulfinic acid and S-methylcysteine sulfoxide. Raney nickel prepared from 100 mg of Al-Ni alloy desulfurized quantitatively up to 40 μmol methionine at 60 °C for 30 min. The desulfurization occurred effectively in the pH range of 7 and 13, but not below 7. Methionine sulfone, cysteic acid, and homocysteic acid were not subject to the reaction. The Raney nickel was deactivated by H2S, and H2O2, or combustion. Desulfurization activity was not enhanced by hydrogen gas.

Group I mGluRs Increase Excitability of Hippocampal CA1 Pyramidal Neurons by a PLC-Independent Mechanism

2002 ◽  
Vol 88 (1) ◽  
pp. 107-116 ◽  
Author(s):  
David R. Ireland ◽  
Wickliffe C. Abraham
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Receptor Subtypes ◽  
Ca1 Pyramidal Neurons ◽  
Group I ◽  
Hippocampal Ca1 ◽  
Group I Mglurs ◽  
Induced Changes

Previous studies have implicated phospholipase C (PLC)-linked Group I metabotropic glutamate receptors (mGluRs) in regulating the excitability of hippocampal CA1 pyramidal neurons. We used intracellular recordings from rat hippocampal slices and specific antagonists to examine in more detail the mGluR receptor subtypes and signal transduction mechanisms underlying this effect. Application of the Group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) suppressed slow- and medium-duration afterhyperpolarizations (s- and mAHP) and caused a consequent increase in cell excitability as well as a depolarization of the membrane and an increase in input resistance. Interestingly, with the exception of the suppression of the mAHP, these effects were persistent, and in the case of the sAHP lasting for more than 1 h of drug washout. Preincubation with the specific mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), reduced but did not completely prevent the effects of DHPG. However, preincubation with both MPEP and the mGluR1 antagonist LY367385 completely prevented the DHPG-induced changes. These results demonstrate that the DHPG-induced changes are mediated partly by mGluR5 and partly by mGluR1. Because Group I mGluRs are linked to PLC via G-protein activation, we also investigated pathways downstream of PLC activation, using chelerythrine and cyclopiazonic acid to block protein kinase C (PKC) and inositol 1,4,5-trisphosphate-(IP3)-activated Ca2+ stores, respectively. Neither inhibitor affected the DHPG-induced suppression of the sAHP or the increase in excitability nor did an inhibitor of PLC itself, U-73122. Taken together, these results argue that in CA1 pyramidal cells in the adult rat, DHPG activates mGluRs of both the mGluR5 and mGluR1 subtypes, causing a long-lasting suppression of the sAHP and a consequent persistent increase in excitability via a PLC-, PKC-, and IP3-independent transduction pathway.

Trans-ACPD, a metabotropic receptor agonist, produces calcium mobilization and an inward current in cultured cerebellar Purkinje neurons

1994 ◽  
Vol 71 (5) ◽  
pp. 1992-1998 ◽  
Author(s):  
D. J. Linden ◽  
M. Smeyne ◽  
J. A. Connor
Keyword(s):  
Dicarboxylic Acid ◽  
Metabotropic Glutamate Receptor ◽  
Pyramidal Cells ◽  
Purkinje Neurons ◽  
Kainate Receptors ◽  
K Channel ◽  
Racemic Mixture ◽  
Tetraacetic Acid ◽  
Metabotropic Receptor ◽  
Inward Current

1. 1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD), a racemic mixture of 1-aminocyclopentane-1S,3R-dicarboxylic acid and 1-aminocyclopentane-1R,3S-dicarboxylic acid, a selective agonist of the metabotropic glutamate receptor, was applied to mouse Purkinje neurons (PNs) in culture. Measurements of free intracellular Ca2+ were made using fura-2 microfluorimetric imaging and of membrane current using perforated-patch voltage-clamp recording in separate experiments. 2. Brief pulses of t-ACPD (< or = 100 microM, 1–5 s) consistently produced a large (200–600 nM) increase in dendritic Ca2+ that was sometimes followed by a somatic increase. The dendrites typically returned to basal Ca2+ levels within 10–30 s. 3. Ca2+ increases produced by t-ACPD were measured in Ca(2+)-free external saline [0.5 mM ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)], suggesting that they result from intracellular mobilization rather than influx. In addition, Ca2+ increases were not attenuated by a mixture of DL-AP5 and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) [antagonists of N-methyl-D-aspartate (NMDA) and AMPA/kainate receptors, respectively], but were almost entirely eliminated by L-AP3 (100 microM), a putative metabotropic receptor antagonist or by preincubation of the cultures in pertussis toxin. 4. Brief pulses of t-ACPD (10 microM) produced a small inward current that was associated with an increase in membrane conductance. This current was reversibly blocked by L-AP3 but not by treatments that attenuate some voltage-gated K+ currents. Thus this current is unlikely to underlie the depolarization that is produced by metabotropic agonists in hippocampal pyramidal cells by K(+)-channel closure. 5. The t-ACPD induced inward current was attenuated by substitution of external Na+ with Li+ or choline, or by application of the membrane-permeable Ca2+ chelator, bis-(2-aminophenoxy)-N,N,N',N'- tetraacetic acid (BAPTA)/AM. One mechanism that could mediate this current is electrogenic Nao/Cai exchange, triggered by Ca2+ mobilization.

Requirement of Protein Synthesis for Group I mGluR-Mediated Induction of Epileptiform Discharges

1998 ◽  
Vol 80 (2) ◽  
pp. 989-993 ◽  
Author(s):  
Lisa R. Merlin ◽  
Peter J. Bergold ◽  
Robert K. S. Wong
Keyword(s):  
Protein Synthesis ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Progressive Increase ◽  
Protein Synthesis Inhibitors ◽  
Burst Frequency ◽  
Metabotropic Glutamate ◽  
Epileptiform Discharges ◽  
Group I

Merlin, Lisa R., Peter J. Bergold, and Robert K. S. Wong. Requirement of protein synthesis for group I mGluR-mediated induction of epileptiform discharges. J. Neurophysiol. 80: 989–993, 1998. Picrotoxin (50 μM) elicited rhythmic synchronized bursting in CA3 pyramidal cells in guinea pig hippocampal slices. Addition of the selective group I metabotropic glutamate receptor (mGluR) agonist ( S)-3,5-dihydroxyphenylglycine (25 μM) elicited an increase in burst frequency. This was soon followed by a slowly progressive increase in burst duration (BD), converting the brief 250–520 ms picrotoxin-induced synchronized bursts into prolonged discharges of 1–5 s in duration. BD was significantly increased within 60 min and reached a maximum after 2–2.5 h of agonist exposure. The protein synthesis inhibitors anisomycin (15 μM) or cycloheximide (25 μM) significantly impeded the mGluR-mediated development of the prolonged bursts; 90–120 min of agonist application failed to elicit the expected burst prolongation. By contrast, the mGluR-mediated enhancement of burst frequency progressed unimpeded. Furthermore, protein synthesis inhibitors had no significant effect on the frequency or duration of fully developed mGluR-induced prolonged discharges. These results suggest that the group I mGluR-mediated prolongation of synchronized bursts has a protein synthesis-dependent mechanism.

Group I mGluR Activation Turns on a Voltage-Gated Inward Current in Hippocampal Pyramidal Cells

2000 ◽  
Vol 83 (5) ◽  
pp. 2844-2853 ◽  
Author(s):  
Shih-Chieh Chuang ◽  
Riccardo Bianchi ◽  
Robert K. S. Wong
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Calcium Currents ◽  
Resting Potential ◽  
Inward Current ◽  
Voltage Gated ◽  
Group I ◽  
Ionic Mechanisms ◽  
Ca3 Pyramidal Cells

A unique property of the group I metabotropic glutamate receptor (mGluR)-induced depolarization in hippocampal cells is that the amplitude of the depolarization is larger when the response is elicited at more depolarized membrane potentials. Our understanding of the conductance mechanism underlying this voltage-dependent response is incomplete. Through the use of current-clamp and single-electrode voltage-clamp recordings in guinea pig hippocampal slices, we examined the group I mGluR-induced depolarization in CA3 pyramidal cells. The group I mGluR agonists ( S)-3-hydroxyphenylglycine and ( S)-3,5-dihydroxyphenylglycine turned on a voltage-gated inward current ( I mGluR(V)), which was pharmacologically distinct from the voltage-gated sodium and calcium currents intrinsic to the cells. I mGluR(V)was a slowly activating, noninactivating current with a threshold at about −75 mV. In addition to the activation of I mGluR(V), group I mGluR stimulation also produced a voltage-independent decrease in the K+conductance. Our results suggest that the depolarization induced by group I mGluR activation is generated by two ionic mechanisms—a heretofore unrecognized voltage-gated inward current ( I mGluR(V)) that is turned on by depolarization and a voltage-insensitive inward current that results from a turn-off of the K+ conductance. The low-threshold and noninactivating properties of I mGluR(V)allow the current to play a significant role in setting the resting potential and firing pattern of CA3 pyramidal cells.

scholarly journals Cell type-specific regulation of inhibition via cannabinoid type 1 receptors in rat neocortex

2013 ◽  
Vol 109 (1) ◽  
pp. 216-224 ◽  
Author(s):  
Claire L. De-May ◽  
Afia B. Ali
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Cell ◽  
Metabotropic Glutamate Receptor ◽  
Pyramidal Cells ◽  
Cb1 Receptor ◽  
Cb1 Receptors ◽  
Cell Type ◽  
Group I ◽  
Cell Type Specific

Endogenous cannabinoid type 1 (CB1) receptors demonstrate a cell type-specific expression and are potent modulators of synaptic transmission within the central nervous system. We aimed to investigate whether two classes of multipolar interneuron in the neocortex displayed a form of short-term synaptic plasticity, depolarization-induced suppression of inhibition (DSI), and whether the DSI was mediated by a common receptor. Paired whole cell recordings combined with biocytin labeling were performed between pyramidal cells and either multipolar adapting or multipolar nonadapting interneurons in layers II–IV of male Wistar rat (postnatal day 17–22) somatosensory cortex. Inhibitory postsynaptic potentials elicited by multipolar adapting interneurons were sensitive to DSI, which was blocked by the CB1 receptor antagonist AM-251 (8 μM), indicating that the suppression of inhibition was mediated by CB1 receptors. Two subpopulations of multipolar nonadapting interneuron-to-pyramidal cell connections were discovered on the basis of their susceptibility to DSI. Whereas 50% were insensitive to DSI, the remaining half were sensitive to DSI, which could not be prevented by AM-251. DSI at these connections was also insensitive to the group I (mGluRIa) and III metabotropic glutamate receptor antagonists ( RS)-1-aminoindan-1,5-dicarboxylic acid (100 μM) and ( RS)-α-cyclopropyl-4-phosphonophenylglycine (100 μM) and the group III agonist l-2-amino-4-phosphonobutanoate (50 μM). However, multipolar nonadapting interneuron-to-pyramidal cell connections were sensitive to the endocannabinoid anandamide (9 μM), mimicking the effects of DSI, which also could not be prevented by AM-251, implying a CB1 receptor-independent suppression of inhibition. These results reveal an interneuron type-specific modulation of synaptic transmission via CB receptors in the neocortex.

scholarly journals Relationship of glutamate and aspartate to the periaqueductal gray-raphe magnus projection: analysis using immunocytochemistry and microdialysis.

1990 ◽  
Vol 38 (12) ◽  
pp. 1755-1765 ◽  
Author(s):  
A J Beitz
Keyword(s):  
Amino Acids ◽  
Excitatory Amino Acid ◽  
Strong Support ◽  
Periaqueductal Gray ◽  
Microdialysis Probe ◽  
Double Labeling ◽  
Homocysteic Acid ◽  
Raphe Magnus ◽  
Projection Analysis ◽  
Relationship Of

This study tested the hypothesis that the excitatory amino acid transmitters glutamate and/or aspartate are associated with the periaqueductal gray (PAG)-raphe magnus (NRM) projection. Retrograde neuroanatomical tracing procedures utilizing the tracers WGA-HRP or D-[3H]-aspartate were combined with immunocytochemical localization of glutamate or aspartate to determine if glutamate and/or aspartate immunostained neurons projected to the NRM. Both glutamate- and aspartate-immunoreactive cells in the PAG were found to project to the NRM. Double labeling immunocytochemichemical procedures indicated that glutamate and aspartate are co-localized in many PAG neurons, suggesting the following possibilities: (a) one of these two amino acids may serve as a precursor to the other; (b) both amino acids may be co-released from the same PAG neuron; or (c) both amino acids are present in high levels in the perikarya for metabolic purposes. At the EM level, both glutamate- and aspartate-immunoreactive terminals were identified in the NRM, strengthening the concept that both amino acids participate in synaptic transmission in this medullary nucleus. To determine if glutamate and aspartate are in fact released from PAG-NRM axons, the PAG was stimulated chemically with homocysteic acid (HCA) and amino acids were collected from the NRM using a microdialysis probe. Microinjection of HCA, but not vehicle, into the PAG resulted in the release of both glutamate and aspartate in the nucleus raphe magnus. These data suggest that both glutamate and aspartate are released from PAG fibers terminating in the NRM and provide strong support for the hypothesis that excitatory amino acids play a neurotransmitter role in the PAG-NRM pathway.

Sign in / Sign up

Export Citation Format

Share Document