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Biomedical subjects

G R Siggins

Publications and source records attributed to G R Siggins.

At least 73 records · Page 4Linked to original sources
PubMed1985

Electrophysiological actions of corticotropin-releasing factor in the central nervous system.

A review of recent studies of the effects of corticotropin-releasing factor (CRF) on the electrical activity of central neurons indicates that CRF has predominantly excitatory actions in locus ceruleus, hippocampus, cortex, and some regions of hypothalamus. These brain areas are reported to contain immunoreactive CRF. Intracellular recordings in the hippocampal slice preparation demonstrate that the excitation in this preparation may arise from reduction of the afterhyperpolarizations (AHPs) following bursts of spikes. The postburst AHPs probably are produced by a Ca2+-dependent K+ conductance. Inasmuch as "Ca2+ spikes" recorded in the presence of tetrodotoxin are not diminished by CRF, this peptide appears to be acting either at the level of the Ca2+-dependent K+ conductance itself, or at the linkage between this conductance and Ca2+ influx or Ca2+ recognition sites. These excitatory effects are consistent with electroencephalographic recordings in awake animals, where intracerebroventricular CRF activates cortical and limbic areas and, at higher doses, evokes epileptiform activity in amygdala and hippocampus. However, predominantly inhibitory actions of CRF have been seen with extracellular single-unit recordings in a few central nervous system (CNS) areas such as lateral septum, thalamus, and the hypothalamic paraventricular nucleus. These findings, combined with those from immunohistochemical, biochemical, and behavioral studies, suggest 1) a possible neuromessenger role for CRF in extrahypothalamic regions and 2) a possible concerted function by CRF-containing elements in the CNS in an integrated behavioral response to stress.

Action Potentials↗
PubMed1983

Rhythmic neuronal activities in the nucleus of the tractus solitarius isolated in vitro.

Coronal slices of the rat medulla were used for an electrophysiological study of the nucleus of the tractus solitarius isolated in vitro. Half of the spontaneously active neurons in the ventral NTS exhibited a rhythmic repetitive spike discharge. In contrast, bursting activity was virtually absent in the isolated NTS. Resetting of repetitive discharges could be obtained by electrical stimulation of the glossopharyngeal-vagal afferent terminals in the tractus solitarius. These results are discussed in relation to the proposed role of the NTS in the neurogenesis of the respiratory rhythm.

Animals↗
PubMed1983

Corticotropin releasing factor decreases postburst hyperpolarizations and excites hippocampal neurons.

Corticotropin releasing factor in concentrations of 15 to 250 nanomoles per liter increased the spontaneous discharge frequency and decreased the size of hyperpolarizations after burst discharges in CA1 and CA3 pyramidal neurons of rat hippocampal slices. Concentrations greater than 250 nanomoles per liter also depolarized the cells. These excitatory actions of corticotropin releasing factor may involve a novel calcium-dependent process.

Action Potentials↗
PubMed1983

Dynorphin-A alters the excitability of pyramidal neurons of the rat hippocampus in vitro.

The effects of dynorphin-A (Dyn) and [Leu5]-enkephalin (Enk) were compared in the vitro hippocampal slice preparation, using extracellular field potential and intracellular voltage recordings. In the CA1 region, Dyn, like Enk, consistently increased the size of the extracellularly recorded population spike (PS) evoked by stratum radiatum (StR) stimulation of the Schaffer collaterals. These responses were naloxone reversible. In contrast, in the CA3 region, Dyn both increased and decreased the PSs evoked by mossy fiber stimulation, whereas Enk slightly enhanced the PS. Intracellular recordings from CA3 pyramidal neurons (HPNs) revealed both excitatory and inhibitory actions of Dyn on spontaneous activity. Associated membrane potential changes were variable. In contrast, Enk had only weak effects on spontaneous activity and no effect on membrane potential. These data suggest regional differences in the effect of Dyn and Enk on hippocampal activity.

Animals↗
PubMed1982

Ethanol and some tetrahydroisoquinolines alter the discharge of cortical and hippocampal neurons: relationship to endogenous opioids.

The activity of single neurons in rat cortex or hippocampus (HPC) was recorded to test two hypotheses: (1) neuronal effects of ethanol are mediated by an endogenous opiate-like mechanism (for example, by release of an endogenous opioid peptide), and; (2) ethanol-induced formation of aldehyde-catecholamine condensation products (tetrahydroisoquinolines; TIQs) might contribute to some acute actions of ethanol. Ethanol and all TIQs were applied to single neurons from multibarrel micropipettes by electroosmosis or pressure. Ethanol most often inhibited neurons of the parietal cortex, while activating most HPC pyramidal neurons. Tetrahydropapaveroline (THP) most often inhibited the spontaneous and glutamate- or acetylcholine (ACh)-induced firing of neurons in both these regions, although some excitations were also seen. In contrast, salsolinol and 7-O-methyl-salsolinol predominantly excited HPC pyramidal neurons, but depressed most parietal cortical neurons. Iontophoretic or SC naloxone usually antagonized the excitatory actions of ethanol, salsolinol and methionine5-enkephalin on HPC pyramidal cells; however, ACh-induced speeding also was antagonized occasionally. Conversely, the antimuscarinic agent scopolamine antagonized the excitatory actions of salsolinol, but not those of met-enkephalin, in some HPC pyramidal cells. These results and those of previous studies show that acutely applied ethanol or salsolinol elicits a region-specific pattern of neuronal effects in brain similar to that previously described for opiates: activity is inhibited in several tested brain areas but excited in hippocampus. Furthermore, these excitatory effects are antagonized by naloxone. However, because of the occasional apparent non-specific effects of naloxone and the puzzling antagonism of the salsolinol-induced excitations by scopolamine, some doubt remains whether the opiate-like actions of these substances can be completely attributed to mediation by opiate receptors.

Animals↗
PubMed1981

Explant cultures of adult amphibian sympathetic ganglia: electrophysiological and pharmacological investigation of neurotransmitter and nucleotide action.

Explant cultures from adult bullfrog sympathetic ganglia can be maintained in vitro for several months and are suitable for electrophysiological recording. The cultured neurons display morphological, electrophysiological and pharmacological characteristics similar, in most respects, to those reported for acutely isolated sympathetic ganglia. Individual cells were visualized by Nomarski optics and impaled with a glass micropipette, which was used for voltage recording and current injection. The average specific membrane properties, calculated from cell dimensions and responses to current injection, were Vm = -46 mV, Rin = 27 M omega, Rm = 1665 omega cm2, tau m = 5 msec, and Cm = 3.2 microF/cm2. Bath perfusion of the cholinergic agonist muscarine depolarized most neurons with an increase in input resistance, while carbachol depolarized neurons with both increases and decreases in input resistance. GABA depolarized all neurons tested with a decreased resistance. High concentrations of catecholamines (2-5 mM) generally hyperpolarized explanted neurons, usually in association with an increased resistance. Extracellularly or intracellularly applied cyclic AMP and two other analogues produced weak and inconsistent hyperpolarizations. In contrast, perfusion or iontophoresis of most non-cyclic purine and pyrimidine nucleotides markedly depolarized most neurons in association with an increased input resistance. UTP and UDP were most potent, revealing threshold concentrations of about 10(-8) to 5 x 10(-8) M. The related nucleosides were largely ineffective. The nucleotide-evoked depolarizations were similar to the muscarine responses but were not blocked by atropine. These results suggest that the purine or pyrimidine nucleotides should be considered for a possible involvement in neurotransmission in sympathetic ganglia.

Animals↗
PubMed1981

Somatostatin hyperpolarizes hippocampal pyramidal cells in vitro.

Superfusion onto hippocampal slices of low concentrations of the tetradecapeptide somatostatin (SS), or an SS analogue having CNS activity, reversibly hyperpolarized pyramidal neurons, as revealed by intracellular recording. The hyperpolarizations were accompanied by reductions in spontaneous and evoked spike discharge and in input resistance; the magnitude of the hyperpolarizations was not influenced by 10 mM MgCl2 added to the perfusate to block synaptic transmission.

Animals↗
PubMed1981

Adenosine depression of hippocampal neurons in vitro: an intracellular study of dose-dependent actions on synaptic and membrane potentials.

In CA1 pyramidal neurons, 5 micrometer adenosine had no measurable effect on resting membrane potential or resistance, while excitatory and inhibitory postsynaptic potentials generated by orthodromic stimulation of the stratum radiatum were reduced by 20--60%. However, 10--20 micrometers adenosine not only markedly reduced (by 20--80%) the synaptic potentials, but also clearly hyperpolarized most pyramidal neurons. This effect was accompanied by a reduction in input resistance in about one-half of the cells and no measurable change in resistance in the rest. Monobutyryl cyclic AMP in concentrations of 50 micrometer or more also hyperpolarized neurons, usually no change in input resistance.

Adenosine↗
PubMed1981

Morphine and opioid peptides reduce inhibitory synaptic potentials in hippocampal pyramidal cells in vitro without alteration of membrane potential.

We used intracellular recording in the hippocampal slice in vitro to characterize further the mechanisms behind the unusual excitatory action of opiates and opioid peptides on hippocampal pyramidal cells in vivo. No significant effect on resting membrane potential, input resistance, or action potential size in cortical area 1 (CA1) pyramidal cells was observed with morphine sulfate, beta-endorphin, [Met5]enkephalin, or [D-Ala2, D-Leu5]enkephalin at 1-50 microM. However, in all cells studied, these agents markedly reduced the size of inhibitory postsynaptic potentials generated by stimulation of the stratum radiatum or alveus. Excitatory postsynaptic potentials were also diminished in many of these cells. The effects of the opioids were antagonized by naloxone. These results are consistent with excitation of pyramidal neurons by a disinhibitory mechanism.

Animals↗
PubMed1981

Electrophysiologic assessment of receptor changes following chronic drug treatment.

Electrophysiological techniques offer a direct cellular approach to questions of neurotransmitter receptor-drug interaction. Although these methods demand considerable technical expertise and advanced instrumentation, as well as satisfaction of certain biological and pharmacological provisos, they are capable of providing detailed information on the functional status of receptors not readily attained from studies on disrupted cell systems. The development of improved methods for the quantitative comparison of changes in transmitter responsiveness after chronic experimental manipulations now makes possible the application of these electrophysiological approaches to current problems in neuropharmacology. This paper reviews the technical and biological considerations that underlie tha analysis of these problems by electrophysiology and illustrates some of the interpretative pitfalls.

Animals↗
PubMed1980

Physiological correlates of ethanol intoxication tolerance, and dependence in rat cerebellar Purkinje cells.

After single injections of ethanol (1-4 g/kg, i.p.), single unit extracellular recordings of rat cerebellar Purkinje cells show dramatically increased frequency of climbing fiber bursts and occasional increases in simple spike firing rate. These effects of ethanol are not observed in rats chronically treated with the substance for 11-14 days: firing patterns 0-3 h after the last ethanol administration do not differ significantly from controls. However, rats chronically treated and then withdrawn from ethanol slow significant, progressive decreases in climbing fiber activity and firing rates from 3 to 32 h after the last ethanol administration. These effects on cerebellar Purkinje cell firing appear to be physiological correlates of the phenomena of ethanol intoxication, tolerance, and dependence.

Alcoholism↗
PubMed1980

An iontophoretic survey of opioid peptide actions in the rat limbic system: in search of opiate epileptogenic mechanisms.

Iontophoretic and micropressure drug application and lesion techniques were used to investigate the cellular source of rat limbic system epileptiform responses to opioid peptides [19]. Iontophoretically applied morphine, methionine enkephalin or beta-endorphin inhibited the spontaneous or glutamate-activated firing of the great majority of single neurons in medial and lateral septum, amygdala and cingulate cortex. These inhibitions in firing were antagonized by iontophoresis of naloxone. In contrast to inhibitory effects in other limbic areas, morphine and the opioid peptides predominantly excited CA1 and CA3 pyramidal neurons in a naloxone-sensitive manner, as previously reported [36]. On rare occasions, iontophoretically applied beta-endorphin evoked repetitive waveforms similar to interictal population EPSPs or spikes. Micropressure application of opiates and peptides also excited hippocampal neurons indicating such responses were not current-induced artefacts. The possible role of the excitatory cholinergic septal hippocampal pathway in the facilitatory response of hippocampal units to the opiates was tested with iontophoretically applied atropine and scopolamine, or lesions of septal nuclei. None of these manipulations reduced the opioid-induced excitations; rather, septal lesions enhanced excitatory and epileptiform responses to the opiates. These results support the hypothesis that opiate-evoked epileptiform activity in the limbic system arises from enhanced pyramidal cell activity in the hippocampal formation, probably by a non-cholinergic mechanism.

Action Potentials↗