Biomedical subjects

N A Lambert

Publications and source records attributed to N A Lambert.

25 records · Page 2Linked to original sources

PubMed1991

Evidence for mu opiate receptors on inhibitory terminals in area CA1 of rat hippocampus.

The mechanism of disinhibition produced by opioid peptides was studied using intracellular recording in area CA1 of rat hippocampal slices. The mu-selective opioid peptide [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAGO) reversibly depressed directly-activated, 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) in a naloxone-sensitive manner. Depression of monosynaptic inhibitory postsynaptic potentials (IPSPs) by DAGO was not prevented by 1-2 mM Ba2+. DAGO reversibly depressed monosynaptic IPSPs when applied locally close to the recording site, but was ineffective when applied close to the stimulating site in stratum radiatum. These results suggest that DAGO disinhibits pyramidal neurons in area CA1 of the rat hippocampus by activating mu opiate receptors located on the terminals of inhibitory neurons, and by a Ba(2+)-insensitive mechanism.

2-Amino-5-phosphonovalerate↗

PubMed1991

Adenosine depresses excitatory but not fast inhibitory synaptic transmission in area CA1 of the rat hippocampus.

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.

2-Amino-5-phosphonovalerate↗

PubMed1991

Hyperpolarizing and depolarizing GABAA receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus.

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 P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35,348; 0.1-1.0 mM). CGP 35,348 (0.1 mM) reversibly blocked late monosynaptic IPSPs and late positive field potentials. These results suggest that fast field potentials are GABAA receptor-mediated population IPSPs (GABAA, fast pIPSPs) and that late field potentials are GABAB receptor-mediated population IPSPs (GABAB, late pIPSPs). 4. Fast pIPSPs were reversibly abolished when the extracellular Cl- concentration [( Cl-]o) was reduced from 132 to 26 mM in parallel with a depolarizing shift in the reversal potential of fast IPSPs. Paired or repetitive stimulation in s. radiatum reversibly depressed fast pIPSPs and fast IPSPs. Paired-pulse depression of fast pIPSPs was reversibly antagonized by CGP 35,348 (0.4-0.8 mM). 5. Laminar analysis of s. radiatum-evoked fast pIPSPs and one-dimensional CSD analysis revealed active current sources in s. radiatum and passive current sinks in s. oriens and s. lacunosum moleculare. S. radiatum sources were abolished by pressure application of BMI in s. radiatum but not in s. oriens. Stimulation in s. oriens, s. pyramidale, or s. lacunosum moleculare evoked GABAA current sources horizontal to the stimulation site. Changes in the dendritic location of inhibitory current with changes in stimulus location paralleled changes in the distribution of excitatory current. 6. In the presence of 4-aminopyridine (50-100 microM), DNQX and APV long-lasting depolarizing GABAA receptor-mediated responses (LLDs) occurred spontaneously or could be evoked. Current sinks associated with s. radiatum-evoked LLDs were located in the same dendritic area as sources associated with hyperpolarizing fast IPSPs.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1990

The actions of 2-hydroxy-saclofen at presynaptic GABAB receptors in the rat hippocampus.

The actions of 2-hydroxy-saclofen (2-OH-S), a recently developed analog of baclofen, were studied at presynaptic GABAB receptors in the rat hippocampal slice. Baclofen (0.5-20 microM) reduces the amplitude of excitatory postsynaptic potentials (EPSPs) recorded from hippocampal CA1 pyramidal neurons. In the presence of 200-500 microM 2-OH-S, the synaptic depressant action of baclofen is significantly reduced. These data show that 2-OH-S is an effective antagonist at presynaptic GABAB receptors on excitatory terminals in the hippocampus.

Animals↗

PubMed1990

Analogs of cyclic AMP decrease gamma-aminobutyric acidA receptor-mediated chloride current in cultured rat hippocampal neurons via an extracellular site.

We have studied the effects of the membrane-permeant cyclic AMP analogs 8-bromo-cyclic AMP and 8-(4-chlorophenylthio)-cyclic AMP (CPT-cAMP) on the gamma-aminobutyric acidA (GABAA) receptor-mediated chloride current in cultured rat hippocampal neurons. External perfusion with 8-bromo-cyclic AMP or CPT-cAMP caused a reversible, concentration-dependent decrease in the response to GABA. Adding the protein kinase inhibitor H-8 to the perfusing medium or the intracellular recording solution did not affect the response to GABA, which was decreased by CPT-cAMP as before. L858051, a water-soluble derivative of the adenylate cyclase activator forskolin, did not decrease the response to GABA even in the presence of the phosphodiesterase inhibitor 3-isobutylmethylxanthine. External cyclic AMP also caused a reversible, concentration-dependent decrease in the response to GABA with a potency similar to that of 8-Br-cAMP. When cAMP was present in the intracellular recording solution cAMP and CPT-cAMP decreased the response to GABA as before. These experiments suggest that analogs of cAMP decrease GABAA receptor-activated chloride current by acting at an extracellular site.

1-Methyl-3-isobutylxanthine↗

PubMed1989

Blockade of the late IPSP in rat CA1 hippocampal neurons by 2-hydroxy-saclofen.

The effects of the GABAB receptor antagonist 2-hydroxy-saclofen were studied using intracellular recording of synaptic potential from CA1 hippocampal neurons. 2-Hydroxy-saclofen (50-200 microM) reversibly blocked the late, GABAB receptor-mediated inhibitory postsynaptic potential (IPSP) but not the early, GABAA receptor-mediated IPSP. In addition, the hyperpolarizing response to baclofen was reduced by similar concentrations of 2-hydroxy-saclofen. This suggests that 2-hydroxy-saclofen is a potent antagonist at postsynaptic GABAB receptors on hippocampal neurons.

Action Potentials↗

PubMed1989

Modification of GABAA receptor function by an analog of cyclic AMP.

Chloride-dependent current responses to gamma-aminobutyric acid (GABA) were recorded from cultured rat hippocampal neurons under voltage clamp. In the presence of the membrane-permeable cyclic AMP analog, 8-bromo-cyclic AMP (8-Br-cAMP), the peak current response to GABA was reduced, although the reversal potential for the current evoked by GABA was unaltered; similar concentrations of 8-bromo-cyclic GMP did not alter the GABA response. 8-Br-cAMP also increased spontaneous activity of the neurons and blocked accommodation of firing. It is possible that the alterations in responses to GABA result from the activation of cyclic AMP-dependent protein kinase (cAMP-PK) and subsequent phosphorylation of the GABAA receptor.

8-Bromo Cyclic Adenosine Monophosphate↗