Ethanol uncouples dentate granule neurons by increasing junctional resistance: a multineuronal system model approach.

The effects of an acute intoxicating concentration of ethanol (50 mM) on the electrotonic membrane properties of hippocampal dentate granule neurons were studied using a system model incorporating electrotonic coupling between neurons. Uncoupling of cells by other alcohols has been shown in several tissues. The system model allows a quantitative estimation of the changes in coupling and other neuronal electrotonic properties.

Muscarinic potentiation of IK in hippocampal neurons: electrophysiological characterization of the signal transduction pathway.

Central cholinergic (muscarinic) systems play an important role in learning and memory. In mammalian central neurons, muscarinic stimulation depresses several voltage-activated K+ currents and modulates synaptic transmission. Using whole-cell voltage-clamp recordings in hippocampal CA1 neurons of rat brain slices, we report that activation of muscarinic receptors potentiates a voltage-activated, sustained K+ current (IK-type).

Electrophysiological actions of acetate, a metabolite of ethanol, on hippocampal dentate granule neurons: interactions with adenosine.

Acetate is the primary breakdown product of ethanol metabolism in the liver and has been found in the brain following ethanol ingestion in rats. Systemically administered acetate has been shown to cause motor impairment, an effect which is blocked by the adenosine receptor blocker, 8-phenyltheophylline (8-PT). The effects of sodium acetate were investigated in this study using intracellular recording techniques in rat hippocampal dentate granule cells, and were compared to the actions of ethanol and adenosine individually and in conjunction with 8-PT.

Patch-clamp study of postnatal development of CA1 neurons in rat hippocampal slices: membrane excitability and K+ currents.

1. The postnatal development of membrane properties and outward K+ currents in CA1 neurons in rat hippocampal slices was studied with the use of whole-cell patch-clamp techniques. 2.

Rearrangement of centromeric satellite DNA in hippocampal neurons exhibiting long-term potentiation.

In situ hybridization in conjunction with three-dimensional reconstruction was used to examine the topology of satellite DNA (sDNA) sequences in hippocampal CA1 neurons. In slices fixed immediately after preparation, 4-5 signals/nucleus were detected in CA1, CA3 and dentate neurons. 70-80% of 154 neurons examined in these 3 areas displayed all signals at the nuclear periphery.

Development of GABA-mediated, chloride-dependent inhibition in CA1 pyramidal neurones of immature rat hippocampal slices.

1. gamma-Aminobutyric acid (GABA)-mediated, Cl(-)-dependent inhibitory postsynaptic potentials (IPSPs) and GABA currents in immature rat hippocampal CA1 neurones were studied using the whole-cell recording technique in brain slices. 2.

Amphetamine actions on pre- and postpubertal rat hippocampal dentate granule neurons.

Clinical evidence suggests different actions of amphetamine (AMPH) in children and adults. Using intracellular recording techniques, the actions of AMPH at 10 and 40 microM were investigated in granule neurons of hippocampal slices from pre- and postpubertal rats. AMPH (10-40 microM) caused depolarization of most postpubertal neurons, often with increased spontaneous activity, whereas most prepubertal neurons were hyperpolarized.

Postsynaptic and presynaptic effects of the calcium chelator BAPTA on synaptic transmission in rat hippocampal dentate granule neurons.

When applied to rat hippocampal slices, the permeable calcium chelator, BAPTA-AM, caused a reduction of both post-spike train slow afterhyperpolarizations (AHPs) and spike-frequency adaptation in dentate granule cells. This indicated that BAPTA-AM can, like microinjected EGTA, block calcium-activated potassium channels. At perforant pathway synapses, BAPTA-AM caused a reduction of inhibitory postsynaptic potentials (IPSPs) and an initial increase and later decrease of excitatory postsynaptic potentials (EPSPs).

Long-term potentiation of synaptic responses in the rat dentate gyrus is due to increased quantal content.

Long-term potentiation (LTP) of synaptic responses in the dentate gyrus neurons of the rat hippocampus was studied in in vitro slices with the use of intracellular recordings. The goal of the study was to determine if the expression of LTP is pre- or postsynaptic. LTP was induced by tetanic stimulation of the perforant pathway in the presence of bicuculline.

Late auditory evoked potentials in alcoholics. Identifying those with a history of epileptic seizures during withdrawal.

The N1-P2 wave of the auditory evoked potential was studied in 19 alcoholics, six of whom had withdrawal seizures on previous admissions. The recordings were made at 1 and 5 days after cessation of drinking. Eight nonalcoholic volunteers were used as controls.

Kindling-induced epilepsy alters calcium currents in granule cells of rat hippocampal slices.

Single electrode voltage-clamp recordings were obtained from dentate gyrus granule cells (GCs) in hippocampal slices of control and commissurally kindled rats. Two types of calcium currents, a transient and a sustained current, were studied in control and kindled neurons. The threshold of the transient calcium current was lowered in kindled GCs.

NMDA depolarizations and long-term potentiation are reduced in the aged rat neocortex.

N-Methyl-D-aspartate (NMDA) responses were recorded intracellularly in layer V neocortical neurons in in vitro slices taken from young (4-6 months) and aged (27-29 months) Fischer 344 rats. Increasing amounts of NMDA produced membrane depolarizations in both groups of cells. The regression analysis showed significantly reduced sensitivity to NMDA in old neurons compared to young.

Whole-cell patch study of GABAergic inhibition in CA1 neurons of immature rat hippocampal slices.

Inhibitory processes mediated by gamma-aminobutyric acid (GABA) were studied in immature rat hippocampal slices using the whole-cell patch clamp technique. Orthodromically evoked hyperpolarizing inhibitory postsynaptic potentials (IPSPs) were observed in CA1 neurons of postnatal 2-5 (P2-5) and 7-13 (P7-13) day old rats under conditions of low internal [Cl-]. In the whole-cell voltage-clamp mode, applications of GABA evoked outwards currents which reversed at -55 mV and -62 mV in P2-5 and P7-13 CA1 neurons, respectively, with comparable reversal potential for the IPSPs for each age.

Phencyclidine actions measured intracellularly in hippocampal CA1 neurons.

The electrophysiological effects of phencyclidine (PCP) were measured intracellularly in guinea pig hippocampal CA1 neurons in vitro. At all doses tested (0.2 microM - 10 mM), PCP increased the width of action potentials (APs).

Serotonin agonist and antagonist actions in hippocampal CA1 neurons.

The actions of serotonin (5-HT) and its putative agonists and antagonists were examined in vitro on hippocampal CA1 neurons using intracellular recordings, demonstrating that the cellular pharmacological effects can not necessarily be predicted from binding characteristics alone. The first response following 5-HT application was often a long-lasting (several minutes) hyperpolarization associated with decreased input resistance. Subsequent 5-HT applications caused only brief hyperpolarizations (30-120 s) and associated decreased input resistance, often followed by membrane depolarization.

Movement disorders in alcoholism: a review.

A wide variety of movement disorders are associated with alcohol abuse. Some idiopathic movement disorders are markedly improved by small amounts of alcohol and this response occasionally may lead to alcoholism. Alcohol abuse alone or combined with hepatic encephalopathy can cause various types of tremor, asterixis, and cerebellar dysfunction.

NMDA and quisqualate reduce a Ca-dependent K+ current by a protein kinase-mediated mechanism.

Stimulation of N-methyl-D-aspartate (NMDA) or quisqualate (Quis) receptors by submicromolar concentrations of NMDA or Quis but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) reduced post-spike train after hyperpolarizations (AHPs) and blocked the underlying Iahp in dentate granule (DG) neurones in vitro. The NMDA but not Quis action was blocked by the NMDA receptor blocker 2-D,L-aminophosphonovaleric acid (APV). Actions of both NMDA and Quis were abolished by isoquinolinesulphonyl-2-methyl-piperazine dihydrochloride (H-7), an inhibitor of several protein kinases.

A glutathione conjugate of hepoxilin A3: formation and action in the rat central nervous system.

Incubation of (8R)- and (8S)-[1-14C]hepoxilin A3 [where hepoxilin A3 is 8-hydroxy-11,12-epoxyeicosa-(5Z,9E,14Z)-trienoic acid] and glutathione with homogenates of rat brain hippocampus resulted in a product that was identified as the (8R) and (8S) diastereomers of 11-glutathionyl hepoxilin A3 by reversed-phase high performance liquid chromatographic comparison with the authentic standard made by total synthesis. Identity was further confirmed by cleavage of the isolated product with gamma-glutamyltranspeptidase to yield the corresponding cysteinylglycinyl conjugate that was identical by reversed-phase high performance liquid chromatographic analysis with the enzymic cleavage product derived from the synthetic glutathionyl conjugate. The glutathionyl and cysteinylglycinyl conjugate are referred to as hepoxilin A3-C and hepoxilin A3-D, respectively, by analogy with the established leukotriene nomenclature.

Large reductions in composite monosynaptic EPSP amplitude following conditioning stimulation are not accounted for by increased postsynaptic conductances in motoneurons.

A compartmental neuronal model was used to show that increased compartmental leak conductances distal to the site of excitatory postsynaptic potential (EPSP) generation have little effect on EPSP amplitude but decrease half-width markedly. Using intracellular recording from cat hindlimb motoneurons, reductions of composite Ia EPSP amplitude by up to 70% unaccompanied by reductions in half-width were seen following conditioning stimuli to hindlimb nerves. Appropriate condition-test intervals produced large reductions in EPSP amplitude that were unaccompanied by detectable increases in motoneuron conductance.

Ethanol tolerance in hippocampal neurons: adaptive changes in cellular responses to ethanol measured in vitro.

The passive and synaptic membrane properties of hippocampal CA1 and dentate gyrus granule neurons have been compared in hippocampal slices obtained from control and ethanol-tolerant rats given ethanol up to 24 hr before sacrifice. In addition, the effects of in vitro exposure to a low concentration (20 mM) of ethanol have been examined in neurons obtained from both groups of animals. No differences were observed in the passive or synaptic membrane properties of dentate granule neurons obtained from control and chronically ethanol-exposed rats.

Parkinsonism in alcohol withdrawal: a follow-up study.

Transient parkinsonism associated with alcohol intake and withdrawal has previously been described. We followed-up three patients with acute alcohol withdrawal-induced parkinsonism 9-11 years after their initial presentation. None showed any evidence of parkinsonism at follow-up.

Acute, withdrawal, and chronic alcohol effects in man: event-related potential and quantitative EEG techniques.

The results presented here strongly suggest that quantitative electroencephalography and event-related potentials are excellent research tools and may be clinically useful as non-invasive monitors of psychotropic drug action and encephalopathies. Our initial data with acute mild alcohol intoxication show that acute tolerance may be reflected in qEEG but not in P3 latency. Since predictably some brain functions may show tolerance, and others not, these approaches may be useful probes.

Late auditory evoked potentials: a method for monitoring drug effects on the central nervous system.

An auditory event-related potential paradigm was designed to objectively quantify the effects of drugs on the central nervous system (CNS). A series of tones was presented at three random interstimulus intervals (ISI). The amplitude of N1-P2 and the recovery of this complex across ISI appear to be rapid, reliable and sensitive measures of changes in brain function associated with drug intake.