Adenosine depresses excitatory but not fast inhibitory synaptic transmission in area CA1 of the rat hippocampus.
Animals; Rats; In Vitro Techniques; Quinoxalines/pharmacology; 2-Amino-5-phosphonovalerate/pharmacology; Membrane Potentials/drug effects; Hippocampus/drug effects/*physiology; Evoked Potentials/drug effects; Synaptic Transmission/*drug effects; Adenosine/*pharmacology; Synapses/*drug effects; Theophylline/analogs & derivatives/pharmacology
The effects of adenosine on inhibitory synaptic transmission in area CA1 were examined using the rat hippocampal slice preparation and intracellular recording. Adenosine did not change fast inhibitory synaptic potentials (IPSPs) but depressed late IPSPs evoked by direct activation of interneurons in the presence of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV). Directly activated IPSPs were unchanged by the selective adenosine A1 receptor antagonist 8-cyclopentyltheophylline (CPT), but CPT reversed hyperpolarization and depression of late IPSPs produced by adenosine. These results indicate that adenosine depresses disynaptic IPSPs in area CA1 by decreasing synaptic activation of inhibitory neurons.
Lambert N A; Teyler T J
Neuroscience letters
1991
1991-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0304-3940(91)90190-5" target="_blank" rel="noreferrer noopener">10.1016/0304-3940(91)90190-5</a>
Effects of extracellular potassium concentration and postsynaptic membrane potential on calcium-induced potentiation in area CA1 of rat hippocampus.
Animals; Rats; Action Potentials/drug effects; Membrane Potentials/drug effects; Potassium/*pharmacology; Hippocampus/drug effects/*physiology; Neuronal Plasticity/*drug effects; Calcium/*pharmacology
Long-lasting potentiation can be induced in area CA1 of hippocampus by a relatively brief (7-10 min) exposure to a higher (4.0 mM) than normal (2.0 mM) extracellular calcium concentration. We have found that long-lasting calcium-induced potentiation is dependent on extracellular potassium concentration. Slices exposed to high extracellular calcium in the presence of normal extracellular potassium (3.35 mM) showed a transient facilitation. Long-lasting potentiation was induced by exposure to high calcium only in slices also exposed to higher than normal extracellular potassium (6.25 mM). In intracellular experiments we found that injection of depolarizing current into postsynaptic neurons could substitute for high extracellular potassium. These results suggest that calcium-induced potentiation involves a postsynaptic, voltage-dependent mechanism. A similar conclusion has been reached for tetanus-induced potentiation. We also found that calcium-induced potentiation, like tetanus-induced potentiation, is not accompanied by an increase in postsynaptic input resistance.
Grover L M; Teyler T J
Brain research
1990
1990-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0006-8993(90)91198-p" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(90)91198-p</a>
Hyperpolarizing and depolarizing GABAA receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus.
2-Amino-5-phosphonovalerate/pharmacology; Animals; Bicuculline/analogs & derivatives/pharmacology; Chlorides/pharmacology; Dendrites/drug effects/*physiology; Evoked Potentials/drug effects; GABA-A Receptor Antagonists; GABA-A/drug effects/*physiology; Hippocampus/*physiology; In Vitro Techniques; Kinetics; Mathematics; Membrane Potentials/drug effects; Models; Neurological; Neurons/drug effects/*physiology; Organophosphorus Compounds/pharmacology; Pyramidal Tracts/drug effects/*physiology; Quinoxalines/pharmacology; Rats; Receptors; Synapses/drug effects/physiology
1. gamma-Aminobutyric acidA (GABAA) receptor-mediated inhibition of pyramidal neuron dendrites was studied in area CA1 of the rat hippocampal slice preparation with the use of intracellular and extracellular recording and one-dimensional current source-density (CSD) analysis. 2. Electrical stimulation of Schaffer collateral/commissural fibers evoked monosynaptic excitatory postsynaptic potentials (EPSPs) and population EPSPs, which were followed by biphasic inhibitory postsynaptic potentials (IPSPs). In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV), stimulation in stratum radiatum evoked monosynaptic fast, GABAA and late, GABAB receptor-mediated IPSPs and fast and late positive field potentials recorded in s. radiatum. 3. Fast monosynaptic IPSPs and fast positive field potentials evoked in the presence of DNQX and APV were reversibly abolished by the GABAA receptor antagonist bicuculline methiodide (BMI; 30 microM) and were not changed by the GABAB receptor antagonist
Lambert N A; Borroni A M; Grover L M; Teyler T J
Journal of neurophysiology
1991
1991-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.1991.66.5.1538" target="_blank" rel="noreferrer noopener">10.1152/jn.1991.66.5.1538</a>
Endogenous mGluR activity suppresses GABAergic transmission in avian cochlear nucleus magnocellularis neurons.
2-Amino-5-phosphonovalerate/pharmacology; Amino Acids/pharmacology; Animals; Chickens/*physiology; Cochlear Nucleus/*cytology/*physiology; Electric Stimulation; Excitatory Amino Acid Antagonists/pharmacology; Excitatory Postsynaptic Potentials/physiology; GABA-B Receptor Agonists; GABA-B Receptor Antagonists; GABA-B/physiology; gamma-Aminobutyric Acid/*physiology; Glycine/analogs & derivatives/pharmacology; In Vitro Techniques; Kinetics; Membrane Potentials/drug effects; Metabotropic Glutamate/agonists/antagonists & inhibitors/*metabolism/physiology; Models; Neurological; Neurons/*physiology; Patch-Clamp Techniques; Receptors; Resorcinols/pharmacology; Synapses/physiology; Synaptic Transmission/*physiology; Xanthenes/pharmacology
GABAergic transmission in the avian cochlear nucleus magnocellularis (NM) of the chick is subject to modulation by gamma-aminobutyric acid type B (GABA(B)) autoreceptors. Here, I investigated modulation of GABAergic transmission in NM by metabotropic glutamate receptors (mGluRs) with whole cell recordings in brain slice preparations. I found that tACPD, a nonspecific mGluR agonist, exerted dose-dependent suppression on evoked inhibitory postsynaptic currents (eIPSCs) in NM neurons. At concentrations of 100 or 200 microM, tACPD increased the failure rate of GABAergic transmission. Agonists for group I (3,5-DHPG, 200 microM), group II (DCG-IV, 2 microM), and group III (L-AP4, 10 microM) mGluRs produced a significant reduction in the amplitude of eIPSCs and a significant increase in failure rate, indicating the involvement of multiple mGluRs in this modulation. The frequency, but not the amplitude, of miniature IPSCs (mIPSCs) was decreased significantly by 3,5-DHPG or DCG-IV. Neither frequency nor amplitude of mIPSCs was affected by L-AP4. mGluR antagonists LY341495 (20 microM) plus CPPG (10 microM) significantly increased the amplitude of eIPSCs, indicating that endogenous mGluR activity suppresses GABA release to NM neurons. Furthermore, blockage of mGluRs increased GABA-evoked discharges recorded under physiological Cl(-) concentrations, whereas tACPD (100 microM) eliminated them. The results indicate that mGluRs play important roles in achieving balanced excitation and inhibition in NM and preserving fidelity of temporal information encoded by NM neurons.
Lu Yong
Journal of neurophysiology
2007
2007-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.00883.2006" target="_blank" rel="noreferrer noopener">10.1152/jn.00883.2006</a>
Activation of metabotropic glutamate receptor 1 dimers requires glutamate binding in both subunits.
Blotting; Calcium Channels/drug effects/metabolism; DNA/biosynthesis/genetics; Dose-Response Relationship; Drug; Fluorescent Antibody Technique; Genes; Glutamic Acid/*metabolism; Humans; Membrane Potentials/drug effects; Metabotropic Glutamate/genetics/*metabolism; myc/genetics; Patch-Clamp Techniques; Plasmids/genetics; Receptors; Signal Transduction/drug effects; Superior Cervical Ganglion/cytology/drug effects/metabolism; Sympathetic Nervous System/cytology/drug effects/metabolism; Western
Group I metabotropic glutamate receptors (mGluRs) form stable, disulfide-linked homodimers. Lack of a verifiably monomeric mGluR1 mutant has led to difficulty in assessing the role of dimerization in the molecular mechanism of mGluR1 activation. The related GABA(B) receptor exhibits striking intradimer cross talk (ligand binding at one subunit effectively produces G protein activation at the other), but it is unclear whether group I mGluRs exhibit analogous cross talk. Signaling of heterologously expressed mGluR1 was examined in isolated rat sympathetic neurons by measuring glutamate-mediated inhibition of native calcium currents. To examine mGluR1 activity when only one dimer subunit has access to glutamate ligand, wildtype mGluR1 was coexpressed with mGluR1 Y74A, a mutant with impaired glutamate binding, and the activity of the heterodimer (mutant/wild type) was examined. The mGluR1 Y74A mutant alone had a dose-response curve that was shifted by about 2 orders of magnitude. The half-maximal dose of glutamate shifted from 1.3 (wild-type mGluR1) to about 450 (mGluR1 Y74A) microM. However, the maximal effect was similar. Wild-type mGluR1 was expressed with excess Y74A mGluR1 to generate a receptor population consisting largely of mutant homodimers and mutant/wild-type heterodimers but without detectable wild-type homodimers. Under these conditions, no glutamate-mediated calcium current inhibition was observed below approximately 300 microM glutamate, although wild-type mGluR1 protein was detectable with immunofluorescence. These data suggest that mutant/wild-type heterodimeric receptors are inactive at ligand concentrations favoring glutamate association with receptor dimers at only one subunit.
Kammermeier Paul J; Yun June
The Journal of pharmacology and experimental therapeutics
2005
2005-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1124/jpet.104.073155" target="_blank" rel="noreferrer noopener">10.1124/jpet.104.073155</a>
The effects of anticonvulsant drugs on long-term potentiation (LTP) in the rat hippocampus.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Anticonvulsants/*pharmacology; Calcium Channel Blockers/pharmacology; Enzyme Inhibitors/pharmacology; Excitatory Amino Acid Agonists/pharmacology; Female; Hippocampus/*drug effects; Isoquinolines/pharmacology; Long-Term Potentiation/*drug effects; Male; Membrane Potentials/drug effects; N-Methylaspartate/pharmacology; Piperazines/pharmacology; Protein Kinase C/antagonists & inhibitors; Rats; Synapses/drug effects
In hippocampal CA1 area, there are at least two forms of long-term potentiation (LTP): one is N-methyl-D-aspartate (NMDA) receptor-dependent LTP (NMDA LTP), which is induced with a 25 Hz tetanus and blocked by 50 microM
Lee G Y; Brown L M; Teyler T J
Brain research bulletin
1996
1996
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0361-9230(95)02041-1" target="_blank" rel="noreferrer noopener">10.1016/0361-9230(95)02041-1</a>
Induction of giant depolarizing potentials by zinc in area CA1 of the rat hippocampus does not result from block of GABAB receptors.
*GABA-A Receptor Antagonists; 2-Amino-5-phosphonovalerate/pharmacology; Animals; Baclofen/pharmacology; Hippocampus/cytology/*drug effects; In Vitro Techniques; Interneurons/drug effects/physiology; Membrane Potentials/drug effects; Quinoxalines/pharmacology; Rats; Synapses/drug effects; Zinc/*pharmacology
The possibility that zinc (Zn2+) induces giant depolarizing potentials (GDPs) by blocking pre- and postsynaptic gamma-aminobutyric acidB (GABAB) receptors in area CA1 of rat hippocampal slices was investigated. Monosynaptic GABAA receptor-mediated fast and GABAB receptor-mediated late inhibitory postsynaptic potentials (IPSPs) were evoked in the presence of the excitatory amino acid (EAA) receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-amino-5-phosphonovalerate (APV). Addition of Zn2+ (0.3 mM) resulted in the appearance of long-lasting GDPs which obscured monosynaptic late IPSPs. The GABAA receptor antagonist bicuculline methiodide (BMI; 30 microM) blocked fast monosynaptic IPSPs and GDPs, revealing a monosynaptic late IPSP that was prolonged in the presence of Zn2+ and blocked by the GABAB receptor antagonist CGP 35,348 (100 microM). The selective GABAB receptor agonist baclofen (10 microM) depressed monosynaptic IPSPs and population excitatory postsynaptic potentials (pEPSPs) by acting at presynaptic GABAB receptors. Depression of synaptic potentials by baclofen was unaffected by Zn2+. These results suggest that induction of GDPs in area CA1 does not result from an action of Zn2+ at GABAB receptors. We suggest instead that Zn2+ induces GDPs by inducing synchronized discharge of GABAergic interneurons.
Lambert N A; Levitin M; Harrison N L
Neuroscience letters
1992
1992-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0304-3940(92)90439-e" target="_blank" rel="noreferrer noopener">10.1016/0304-3940(92)90439-e</a>
Cholinergic disinhibition in area CA1 of the rat hippocampus is not mediated by receptors located on inhibitory neurons.
2-Amino-5-phosphonovalerate/pharmacology; Action Potentials/drug effects; Adenosine/pharmacology; Animals; Baclofen/pharmacology; Carbachol/pharmacology; Cholinergic/*drug effects; Evoked Potentials/drug effects; GABA-A Receptor Antagonists; Hippocampus/*drug effects; In Vitro Techniques; Membrane Potentials/drug effects; Neurons/*drug effects; Parasympathetic Nervous System/*drug effects; Phorbol Esters/pharmacology; Quinoxalines/pharmacology; Rats; Receptors; Synaptic Transmission/physiology
We studied the effects of carbamylcholine (carbachol; CCh) on monosynaptic inhibitory postsynaptic potentials (IPSPs) evoked in the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV). CCh (30 microM) blocked late afterhyperpolarizations but did not depress GABAA receptor-mediated fast monosynaptic IPSPs or GABAB receptor-mediated late monosynaptic IPSPs. In the presence of CCh the GABAB receptor agonist (+/- )-baclofen (2 microM) reversibly hyperpolarized pyramidal neurons and depressed monosynaptic IPSPs as under control conditions. Phorbol-12,13-diacetate (PDAc; 10 microM) increased fast and depressed late monosynaptic IPSPs, and prevented depression of IPSPs by baclofen. These results suggest that cholinergic disinhibition in area CA1 of the hippocampus results from decreased synaptic excitation of inhibitory neurons.
Lambert N A; Teyler T J
European journal of pharmacology
1991
1991-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0014-2999(91)90801-v" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(91)90801-v</a>