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J H Ashe

Publications and source records attributed to J H Ashe.

At least 37 records · Page 2Linked to original sources
PubMed1989

Argiotoxin-636 blocks excitatory synaptic transmission in rat hippocampal CA1 pyramidal neurons.

Argiotoxin 636, (AR636), a synaptic antagonist from orb weaver spider venom, is shown to produce reversible blockade of excitatory transmission in CA1 pyramidal neurons of the in vitro rat hippocampus. Microtopical application of AR636 (5-50 nM) resulted in a concentration-dependent suppression of the amplitude of the dendritic field EPSP recorded from stratum radiatum, and the amplitude of the population spike recorded from stratum pyramidale in response to stimulation of the Schaffer collaterals. The maximum effect of AR636 occurred at about 15-25 min. These effects were reversible after washing with toxin-free physiological solution with the rate of recovery having an inverse relationship to the concentration of AR636. In contrast to the effects observed with orthodromic stimulation, the amplitude of the antidromic spike was not affected by exposure to AR636. The temporal pattern of GABAergic paired-pulse inhibition was unaffected by exposure to AR636. Neuronal discharge elicited by pressure ejection of L-glutamate was abolished by AR636, whereas, responses to L-aspartate were not significantly affected. These data suggest that AR636 functions as a selective antagonist of glutamate-mediated synaptic transmission in rat hippocampus.

Action Potentials↗
PubMed1989

Cholinergic modulation of frequency receptive fields in auditory cortex: I. Frequency-specific effects of muscarinic agonists.

Previously we reported that acetylcholine (ACh) and acetyl-beta-methacholine (MCh) modify responses of neurons in auditory cortex to individual frequencies. The purpose of this study was to determine whether muscarinic agonists produce frequency-specific alterations or general changes in cellular responses. Frequency-specific modifications would be evident in alterations of frequency receptive fields (FRF) that differed across frequencies while general effects would be seen as changes that were more or less the same over frequencies. Responses of single neurons to designated sets of tones were recorded in the auditory cortex of chronically prepared awake cats before, during, and following ejection of ACh or MCh by iontophoresis or micropressure using multibarrel micropipettes. Frequency receptive fields were determined by presenting isointensity tones across a range of frequencies including the cell's best frequency (BF) to tone onset. FRF for "off" and "sustained (through)" responses were also determined quantitatively. The effects of ACh and MCh were predominantly frequency-specific (77%, 39/51 cells); general changes (19%, 10/51) and no effects (4%, 2/51) were less likely. Frequency-specific effects involved both facilitation and reduction of the same response component to different frequencies within the same neuron. For responses to tone onset (but not "through" and "off" responses), agonists were more likely to produce a decrease at the BF while simultaneously increasing responses to other frequencies. Agonists could increase or decrease frequency selectivity. Effects of agonists could be blocked by atropine, suggesting involvement of muscarinic receptors.

Acetylcholine↗
PubMed1989

Cholinergic modulation of frequency receptive fields in auditory cortex: II. Frequency-specific effects of anticholinesterases provide evidence for a modulatory action of endogenous ACh.

Exogenously applied muscarinic agonists--for example, acetylcholine (ACh) and acetyl-beta-methacholine (MCh)--modify frequency receptive fields in auditory cortex of unanesthetized animals in a frequency-specific rather than global manner. The present study sought to relate these findings to endogenous actions of ACh by using the anticholinesterase agents eserine sulphate and soman (0-1,2,2-trimethylpropylmethylphosphonofluoridate) to facilitate the effects of endogenous ACh. Frequency receptive fields (FRF) were determined by presenting sequences of different isointensity tones before, during, and after application of ACh, MCh, eserine, or soman; also the cholinesterase blockers were applied between applications of ACh or MCh. The major effects produced by the inhibitors were similar to those of the agonists. Predominant effects were frequency-specific changes in FRF. Further, eserine and soman, similar to ACh and MCh, produced shifts in the best frequency (BF) of FRF due mainly to coordinated depression of responses to the BF and increased responses to adjacent, non-BF. The results indicate that exogenous and endogenous ACh, acting via muscarinic receptors, can significantly influence the physiological functioning of cortical neurons and consequently their processing of sensory information.

Acetylcholine↗
PubMed1988

Muscarinic agonists modulate spontaneous and evoked unit discharge in auditory cortex of cat.

The present experiments studied the effects of cholinergic agonists and antagonists on the spontaneous and acoustic-evoked discharge of auditory cortical neurons and examined whether these effects were mediated by muscarinic cholinergic receptors. A primary focus of this report is the analysis of specific effects of these agents on the spontaneous and tone-evoked discharge and on different temporal components of the evoked discharge. Single neurons were recorded in the auditory cortex of chronically prepared, awake cats with multibarrel micropipette electrodes. The responses to acoustic stimuli were obtained before, during, and following continuous ejection of cholinergic agonist or antagonists by micropressure. The mean rate of discharge of the neurons was analyzed quantitatively for spontaneous discharge and for different peaks of the tone-evoked PSTH corresponding to tone "on," "through," and "off" responses. Acetylcholine (ACh) and acetyl-beta-methacholine (MCh) produced significant effects on spontaneous activity in 72% and 68% of neurons tested, respectively. Tone-evoked responses were effected in 92% and 82% of cells tested, respectively. The ability of these agonists to modify spontaneous or evoked activity was dose-dependent. Agonist effects on spontaneous and evoked activity were often different in the same cell; however, effects on spontaneous activity did predict effects on "through" responses. The most common effect of ACh or MCh on evoked activity was facilitation of the tone "on" response. For neurons with multicomponent discharge patterns in response to tones, the agonists had nonuniform effects on different response components. However, the effects of ACh on the "on" and "off" responses covaried. Hence cholinergic agonists produce heterogeneous, selective effects on different components of the responses of auditory cortical neurons rather than simple increases or decreases in discharge level. The effects of cholinergic agonists were modified in the presence of atropine. The effects of MCh were blocked by atropine in a higher proportion of cases than those of ACh.

Acetylcholine↗
PubMed1988

Modification of nicotinic ganglionic transmission by muscarinic slow postsynaptic potentials in the in vitro rabbit superior cervical ganglion.

The influence of slow muscarinic postsynaptic potentials, i.e., the s-IPSP and s-EPSP, on synaptic transmission mediated through nicotinic receptors was studied in the superior cervical ganglion of the rabbit. Postganglionic spikes and synaptic potentials were elicited by delivery of conditioning and test stimulus pulses to afferent fibers. When paired stimulus volleys were separated by brief intervals (20-100 msec) or long intervals (1,000-8,000 msec), the population spike elicited by the test stimulus was larger in amplitude than that elicited by the conditioning volley. When paired stimulus volleys were separated by 250-500 msec, the amplitude of the population spike elicited by the test volley was smaller than that elicited by the conditioning stimulus. Gallamine, which selectively blocks the s-IPSP, reduced the suppression of the test spike which occurred when stimulus IPIs ranged between 250-500 msec. Pirenzepine, which selectively blocks the s-EPSP, reduced the late facilitation of test postganglionic spikes which occurred with stimulus IPIs greater than 1,000 msec. The non-selective muscarinic antagonist QNB, produced changes in postganglionic spike amplitude that were similar to the combined effects of gallamine and pirenzepine. The evidence indicates that the s-IPSP and s-EPSP modified the excitability state of the ganglionic neurons and subsequent synaptic transmission that was mediated through nicotinic receptors.

Action Potentials↗
PubMed1988

AF-DX 116: a selective antagonist of the slow inhibitory postsynaptic potential and methacholine-induced hyperpolarization in superior cervical ganglion of the rabbit.

AF-DX 116 [11-([2-[(diethylamino)methyl]-1-piperdinyl]acetyl)-5, 11-dihydro-6H-pyrido[2,3-b][1,4]benzodiaze pine-6-one], a muscarinic receptor antagonist that divides the M2-type muscarinic receptor into additional functional classes, modified muscarinic responses recorded from the superior cervical ganglion of the rabbit with sucrose or air gap techniques. Incubation of ganglia with AF-DX 116 suppressed the amplitude of the slow-inhibitory postsynaptic potential (s-IPSP) in a concentration-dependent and highly specific manner. At concentrations which reduced the amplitude of the s-IPSP by 80 to 90%, there was no significant reduction of the amplitudes of the muscarinic slow-excitatory postsynaptic potential or the nicotinic fast-excitatory postsynaptic potential. In addition, superfusion of ganglia with AF-DX 116 resulted in the concentration-dependent suppression of ganglionic hyperpolarization induced by methacholine without suppression of methacholine-induced depolarization. Ganglionic hyperpolarization that was produced by norepinephrine was unaffected by AF-DX 116. Increasing the level of acetylcholine available for interaction with muscarinic receptors by increasing the number of stimulus volleys that were applied to the preganglionic nerve resulted in a parallel shift, to the right, of the concentration-response curve for suppression of the s-IPSP by AF-DX 116. Similarly, incubation of ganglia with the specific antiacetylcholinesterase, BW 284 (1-5-bis[4-allyl dimethylammonium phenyl]pentan-3 one dibromide), increased the concentration of AF-DX 116 that was required to produce a comparable suppression of the s-IPSP. These results indicate that the s-IPSP in mammalian superior cervical ganglion involves an action of acetylcholine at the M2 type receptor that is preferentially blocked by AF-DX 116.

Animals↗
PubMed1987

Antagonist discrimination of two muscarinic responses elicited by applied agonists and orthodromic stimuli in superior cervical ganglion of rabbit.

Pirenzepine and gallamine selectively and differentially antagonized two muscarinic responses, in the superior cervical ganglion of the rabbit, whether elicited by the muscarinic agonist methacholine or by orthodromic stimulation. Methacholine elicited a biphasic ganglionic response, consisting of hyperpolarizing and depolarizing components that were the agonist-induced equivalents of the slow-inhibitory and slow-excitatory postsynaptic potentials elicited by orthodromic stimulation. Superfusion of ganglia with pirenzepine resulted in a concentration-dependent suppression of depolarization induced by methacholine with no suppressant action on ganglionic hyperpolarization. In contrast, superfusion of ganglia with gallamine resulted in a concentration-dependent suppression of ganglionic hyperpolarization and the slow-inhibitory postsynaptic potential. These effects occurred without appreciable suppression of ganglionic depolarization or the slow-excitatory postsynaptic potential. The action of gallamine was specific for muscarinic hyperpolarization. Hyperpolarizations produced by superfusion with dopamine or norepinephrine were unaffected by gallamine, at concentrations that suppressed the muscarinic slow-inhibitory post-synaptic potential. Incubation with anti-cholinesterases produced a parallel shift, to the right, of concentration-response curves for suppression by gallamine of the slow-inhibitory postsynaptic potential. This was presumably the consequence of an increase in the acetylcholine available for interaction with the muscarinic receptor. The evidence suggests that the ability of gallamine and pirenzepine to suppress selectively the slow-inhibitory and slow-excitatory postsynaptic potentials, as previously demonstrated, is through an action at muscarinic receptors. Furthermore, the data suggest that these pharmacological agents produce their effects by interaction at different muscarinic recognition sites.

Animals↗
PubMed1985

Responses of opossum and rat hippocampal CA1 cells to paired stimulus volleys.

Short-term synaptic plasticity was studied in the in vitro hippocampus of the North American opossum (Didelphis virginiana) and rat (Rattus norvegicus). Conditioning and test stimulus pulses were delivered to fibers in stratum radiatum, and intracellular and extracellular recordings were obtained from area CA1 pyramidal cells. In rat, the amplitude of the population spike in response to the second (test) of two stimulus impulses is suppressed at short inter-pulse-intervals (IPI's). In opossum, the amplitude of the test population spike is facilitated at comparable IPI's. Facilitation of the test population spike in rat occurs only when the test stimulus is separated from the first stimulus (conditioning) by a longer IPI. Peak values of facilitation do not significantly differ between species. Intracellular responses, elicited by stimulus pulses that were subthreshold for spike production, indicate that the amplitude of test EPSP's recorded from opossum pyramidal cells are facilitated at IPI's that result in suppression of test EPSP's in rat pyramidal cells.

Animals↗
PubMed1984

Modulation by dopamine of population responses and cell membrane properties of hippocampal CA1 neurons in vitro.

Dopamine (DA) was applied to rat hippocampal slices maintained in vitro. Extracellular and intracellular recording techniques were used to study the effect of DA on population responses, membrane potentials, and membrane responses to hyperpolarizing current pulses in CA1 pyramidal cells. Temporary exposure of hippocampal slices to DA has a dual effect. The initial action of DA is to produce a suppression of the extra-cellularly recorded population responses. In individual neurons, this initial effect is seen as a membrane hyperpolarization accompanied by a decrease in the amplitude of responses to hyperpolarizing current pulses. The frequency of occurrence of spontaneous depolarizations and spikes is reduced. The early action of DA is followed by a profound potentiation of the population responses that can last for hours. This long-lasting potentiation of the population response, induced by DA, is depressed by spiroperidol, a DA antagonist. In individual neurons, the late effect of DA is a long-lasting membrane depolarization associated with an increase in the amplitude of responses to hyperpolarizing current pulses. During this late phase, spontaneous activity is increased, as are single cell responses to stimulation of afferents. The evidence presented here indicates that DA is able to induce a long-lasting modification of the excitability of CA1 hippocampal neurons. This modulation of excitability by DA may be similar in nature to previously described DA-modulatory actions in the peripheral nervous system.

Animals↗
PubMed1984

Effect of inhibitors of protein synthesis on dopamine modulation of the slow-EPSP in rabbit superior cervical ganglion.

The protein synthesis inhibitors, anisomycin and cycloheximide, were tested for their ability to prevent dopamine-induced long-term enhancement of the slow-EPSP in rabbit superior cervical ganglion. Exposure of ganglia to either inhibitor of protein synthesis, at a concentration that suppressed [3H]leucine incorporation into ganglionic protein by at least 95%, had no effect on the development of dopamine-induced enhancement of the slow-EPSP. Incubation of ganglia with dopamine, without an inhibitor of protein synthesis, was without effect on [3H]leucine incorporation into ganglionic protein. It is concluded that synthesis of new protein is not required for the development of long-term enhancement of the slow-EPSP induced by dopamine.

Animals↗
PubMed1984

Modulation by dopamine of population spikes in area CA1 hippocampal neurons elicited by paired stimulus pulses.

Extracellular recording techniques were used to study the effects of dopamine on postactivation excitability of rat area CA1 hippocampal neurons maintained in vitro. Population spikes were elicited by delivery of conditioning and test stimulus pulses to afferent fibers. The interval between the conditioning and test volley was set to separate delivery of stimuli by 10 to 80 msec. The effect of superfusion or microtopical application of dopamine (DA) on population responses to test stimulus pulses was studied. When paired stimulus volleys, separated by brief intervals (up to 40 msec), were delivered to afferent fibers, paired-pulse suppression (PPS) was indicated by the amplitude of the population spike elicited by the test volley being smaller than that elicited by the conditioning volley. When paired volleys were separated by longer intervals (40 to 80 msec), the response elicited by the test volley was larger in amplitude than that elicited by the conditioning volley, indicating paired-pulse facilitation (PPF). Following exposure to DA, the amplitude of the population response elicited by the conditioning volley was larger than the amplitude before exposure to DA. This effect was long-lasting, enduring for tens of minutes. However, when the amplitude of the conditioning population response was held constant, the PPS was decreased, indicating disinhibition. It is suggested that dopamine produces a long-lasting attenuation of an intervening inhibitory influence onto CA1 pyramidal neurons.

Animals↗
PubMed1984

Differential and selective antagonism of the slow-inhibitory postsynaptic potential and slow-excitatory postsynaptic potential by gallamine and pirenzepine in the superior cervical ganglion of the rabbit.

Two cholinergic antagonists, gallamine and pirenzepine, agents that have been shown to bind selectively to different subpopulations of the muscarinic receptor, were found to antagonize selectively and differentially the amplitudes of the slow-inhibitory and slow-excitatory postsynaptic potentials in the superior cervical ganglion of the rabbit. Incubation of ganglia with gallamine resulted in a concentration-dependent suppression of the slow-inhibitory postsynaptic potential. The pharmacological action of gallamine was highly specific. At concentrations which reduced the amplitude of the slow-inhibitory postsynaptic potential by as much as 70-90%, there was no reduction of the amplitudes of the muscarinic slow-excitatory postsynaptic potential, the nicotinic fast-excitatory postsynaptic potential, noncholinergic slow-slow-excitatory postsynaptic potential, or post-stimulus hyperpolarizing afterpotentials. The amplitude of the slow-excitatory postsynaptic potential was actually facilitated in the presence of gallamine, presumably as a result of suppression of the overlapping slow-inhibitory postsynaptic potential. In contrast to the action of gallamine, pirenzepine produced a selective suppression of the amplitude of the slow-excitatory postsynaptic potential. Pirenzepine had very little influence on the amplitude of the slow-inhibitory postsynaptic potential at concentrations sufficient to reduce the amplitude of the slow-excitatory postsynaptic potential by as much as 50%, and had no effect on the amplitudes of the nicotinic fast-excitatory postsynaptic potential or noncholinergic slow-slow-excitatory postsynaptic potential. The evidence presented suggests that multiple muscarinic recognition sites, previously identified by studies of the affinities of pharmacological agents for the muscarinic receptor, may actually be involved in synaptic transmission and functionally coupled to cellular effector mechanisms.

Animals↗
PubMed1983

Ganglionic slow postsynaptic potentials and muscarinic asynchronous discharge in postganglionic nerve elicited by orthodromic stimulation.

Simultaneous recordings of the slow postsynaptic potentials of in vitro rabbit superior cervical ganglion and the muscarinic asynchronous discharge in the postganglionic nerve were obtained in order to examine their relationship. Analyses for linear correlation indicated that the peak amplitude of the S-EPSP cannot fully determine the maximum rate of muscarinic asynchronous discharge. The rate of asynchronous discharge in the postganglionic nerve systematically increased with increases in either the frequency or duration of preganglionic stimulation even after the S-EPSP was at asymptotic levels. We suggest that this deviation from linearity is the result of repetitive spike discharge elicited by the S-EPSP. The S-IPSP had no apparent influence on generation of asynchronous afterdischarge, but may have had an influence on asynchronous discharge occurring during a train of stimuli. Incubation of ganglia with gallamine, an antagonist of the ganglionic muscarinic receptors mediating hyperpolarization, resulted in the selective blockade of the S-IPSP. Neither the S-EPSP nor the muscarinic afterdischarge were suppressed by muscarinic receptor blockade by gallamine, nor did gallamine produce any effect on the nicotinic F-EPSP or the noncholinergic SS-EPSP. Temporary exposure of ganglia to dopamine, in the presence of an inhibitor of catechol-O-methyltransferase, was followed by a potentiation of the muscarinic afterdischarge in accordance with the long-term enhancement reported for the S-EPSP.

Action Potentials↗
PubMed1982

Pharmacological properties and monoaminergic mediation of the slow IPSP, in mammalian sympathetic ganglion.

Phenoxybenzamine can selectively eliminate the s-IPSP, in the presence of anti-cholinesterases that enhance s-IPSP and s-EPSP; and the alpha 2-antagonist, yohimbine, can partially but consistently depress s-IPSP selectively. The results provide positive pharmacological support for the monoaminergic nature of the transmitter for s-IPSP in mammalian sympathetic ganglia and argue against suggestions that the s-IPSP is a direct hyperpolarizing response to acetylcholine.

Animals↗
PubMed1982

Metoclopramide mimics a D-1 type of dopamine action in rabbit superior cervical ganglion.

Metoclopramide (MCP) in a sufficiently high concentration (100 microM) induced a large and persisting potentiation of slow-excitatory postsynaptic potentials (s-epsp) and slow-inhibitory postsynaptic potentials (s-epsp) but depressed in fast epsp. This modulatory action of metoclopramide was markedly suppressed by (+)-butaclamol (7 microM) and, to a lesser extent, by spiroperidol (2.5-4 microM). Metoclopramide also possessed weak anti-acetylcholinesterase activity(I50% = 245 microM; measured by Dr N. Inestrosa), but this was shown not to account for the potentiating actions of metoclopramide. Thus, although metoclopramide is a D-2 antagonist, it appears to mimic the D-1 action of dopamine in modulating the slow psps.

Action Potentials↗
PubMed1981

Modulation of slow postsynaptic potentials by dopamine, in rabbit sympathetic ganglion.

(1) Temporary exposure of rabbit's superior cervical ganglion (SCG) to dopamine (DA), in the presence of an inhibitor of catechol-o-methyltransferase (COMT) is consistently followed by a potentiation of the slow (s)-EPSP and s-IPSP, lasting for some hours. The fast (f)-EPSP is not significantly increased, but it is better maintained than in control ganglia. (2) Exposure to the COMT-inhibitor U-0521 alone induces less but substantial potentiations of both s-PSPs. This effect is explained as due to protection of DA released intraganglionically at rest. (3) This evidence suggests that COMT may significantly limit the access of catecholamines to postsynaptic receptors, for at least certain types of neuron-to-neuron synaptic actions. (4) The potentiation of both s-PSPs, whether induced by DA in the presence of U-0521 or by U-0521 alone, is depressed by DA-1 antagonists that have been found to depress DA-stimulation of adenyl cyclase in rabbit SCG; these are spiroperidol, butaclamol and, to a lesser extent, bromocriptine. The specific 'DA-2' antagonists metoclopramide and sulpiride, and the alpha-adrenergic antagonist dihydroergotamine, did not depress potentiation. (5) Potentiation of s-EPSP is viewed as identical in nature to the previously discovered DA-modulatory enhancement of direct muscarinic depolarizing actions (by acetylcholine or its agonists). Potentiation of s-IPSP may be due to a similar DA-modulation of other muscarinic response(s) involved in mediating the s-IPSP. The consistency and comparative ease with which these DA-modulatory effects can be induced, under presently described experimental conditions, should facilitate future study of this mode of synaptic action.

Animals↗
PubMed1981

Orthodromic production of non-cholinergic slow depolarizing response in the superior cervical ganglion of the rabbit.

1. A late slow depolarization in the rabbit superior cervical ganglion, recorded extracellularly as ;late late negative' (l.l.n.) response, can be elicited by suitably repetitive stimulation of cervical sympathetic nerve. The l.l.n. response is not blocked by strong nicotinic, muscarinic or adrenergic antagonists; it appears with latencies in seconds, rise times in minutes, durations of up to 20 min or more, and extracellular amplitudes that can exceed 1 mV when recorded in an air-gap chamber.2. The l.l.n. component is a graded post-synaptic response that decreases with a length constant similar to those of the known p.s.p.s (fast e.p.s.p., slow i.p.s.p., and slow e.p.s.p.). This and its other characteristics indicate that the l.l.n. response is neuronally generated and represents a non-cholinergic late slow depolarization. The term ;slow slow e.p.s.p.' is suggested for this response, to replace both ;slow depolarization' and ;late slow e.p.s.p.'.3. The amplitudes, evaluated relative to the compound action potentials, and the durations of l.l.n. responses recorded from intact neurones of rabbit superior cervical ganglion were considerably greater and more consistently producible than the non-cholinergic slow depolarizations recorded by others from impaled neurones of guinea-pig inferior mesenteric ganglion.4. The l.l.n. response does not exhibit the special sensitivity to sodium azide previously found for the muscarinic ;late negative' or slow e.p.s.p. response.5. The total number of orthodromic volleys is the chief determinant of the amplitude and duration of the l.l.n. response. Increases in pulse frequency, with no change in pulse number, exert only a minor influence on amplitude and duration of the l.l.n. response but can markedly decrease latency and rise time.6. Even very low pulse frequencies (e.g. 1/sec) are almost as effective as higher frequencies if a sufficiently large number of stimulus pulses is applied.7. The features of orthodromic production of the l.l.n., slow slow e.p.s.p. response, as well as the amplitudes and durations of this depolarization, indicate that this non-cholinergic post-synaptic response could, like the muscarinic slow e.p.s.p., play a significant role in mediating physiological activities of sympathetic ganglia.

Animals↗