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D V Madison

Publications and source records attributed to D V Madison.

At least 37 records · Page 2Linked to original sources
PubMed1993

Enhancement of transmission at the developing retinogeniculate synapse.

Axon terminals from retinal ganglion cells in the left and right eyes initially overlap with each other in the lateral geniculate nucleus of the neonatal ferret, then segregate into eye-specific layers via an activity-dependent process. Brain slices were used to show that, during this period of reorganization, retinal terminals within the lateral geniculate nucleus evoke excitatory postsynaptic currents composed of both NMDA and non-NMDA receptor-mediated currents. The amplitude of these currents could be enhanced for several tens of minutes to more than an hour by several bursts of high frequency synaptic stimulation, and the induction of enhancement appears to depend on NMDA receptor activation. Synaptic enhancement such as this could provide one of the physiological mechanisms by which retinal terminals segregate into eye-specific layers during development.

Animals↗
PubMed1993

Phorbol esters enhance synaptic transmission by a presynaptic, calcium-dependent mechanism in rat hippocampus.

1. The effects of phorbol esters on evoked and spontaneous excitatory neurotransmission were studied in the CA1 area in the in vitro hippocampal slice preparation of the rat. Experiments were conducted using field potential recording and whole-cell voltage clamp of CA1 pyramidal neurons. 2. Pyramidal cells dialysed during whole-cell recording with EGTA-containing electrode solutions, unable to support the induction of long-term potentiation (LTP), still showed robust phorbol ester-induced potentiation of excitatory synaptic transmission. 3. Spontaneous miniature excitatory postsynaptic currents (EPSCs), recorded in whole-cell voltage clamp in the presence of tetrodotoxin and picrotoxin, had amplitudes ranging from 4 to 40 pA and occurred at an average frequency of 0.8-5 Hz. Neither the amplitude nor the frequency of spontaneous EPSCs was altered by cadmium, dihydropyridines, or omega-conotoxin GVIA. 4. The phorbol ester 4-beta-phorbol 12,13-diacetate increased the frequency of spontaneous miniature EPSCs without changing the shape of the EPSC amplitude distribution, suggesting that phorbol esters exert their potentiating effects presynaptically. 5. Blockade of voltage-dependent calcium channels with cadmium attenuated the phorbol-induced increase in spontaneous miniature EPSCs frequency. The phorbol ester-induced increase in miniature EPSC frequency was also attenuated by dihydropyridines, but not by omega-conotoxin GVIA. 6. Unlike spontaneous synaptic currents, stimulus-evoked synaptic currents were reduced by omega-conotoxin but not by nifedipine. 7. We conclude that the phorbol ester increases spontaneous release of glutamate by modulating an L-type channel that does not participate in stimulus-evoked neurotransmitter release.

Action Potentials↗
PubMed1992

Isoproterenol increases the phosphorylation of the synapsins and increases synaptic transmission in dentate gyrus, but not in area CA1, of the hippocampus.

Previous studies have shown that either norepinephrine (NE) or isoproterenol (ISO) enhances the slope of the field excitatory postsynaptic potential (EPSP) in the dentate gyrus of the rat hippocampal formation. In contrast, NE and ISO cause no increase in excitatory transmission in area CA1 of the hippocampus. The molecular mechanism underlying this brain region-specific increase in synaptic transmission is not known. The phosphorylation of synapsin I and synapsin II, two homologous presynaptic vesicle-associated proteins, is thought to promote neurotransmitter release. The authors have observed previously NE- and ISO-enhanced phosphorylation of synapsins I and II in the dentate gyrus. The purpose of this study was to determine whether ISO-stimulated phosphorylation also occurs in the CA1, where ISO has no effect on excitatory neurotransmission. These studies were correlated with electrophysiological studies in in vitro hippocampal slices. Superfusion of slices with ISO resulted in an increase in EPSP slope in the dentate but not in area CA1. The enhanced dentate EPSP returned to baseline levels within 30 minutes of washout of the drug. Isoproterenol produced corresponding increases in the phosphorylation of the synapsins in dentate slices but had no effect on these proteins in CA1 slices. Moreover, in dentate slices exposed to a 30-minute wash following incubation with ISO, phosphorylation of the synapsins returned to control levels. This close temporal and brain regional correlation between ISO stimulation of both synapsin phosphorylation and synaptic transmission suggests that the synapsin proteins may play a role in the synaptic potentiation produced by ISO in the dentate.

Animals↗
PubMed1992

Opioid inhibition of GABA release from presynaptic terminals of rat hippocampal interneurons.

Opiates and the opioid peptide enkephalin can cause indirect excitation of principal cortical neurons by reducing inhibitory synaptic transmission mediated by GABAergic interneurons. The mechanism by which opioids mediate these effects on interneurons is unknown, but enkephalin hyperpolarizes the somatic membrane potential of a variety of neurons in the brain, including hippocampal interneurons. We now report a new, more direct mechanism for the opioid-mediated reduction in synaptic inhibition. The enkephalin analog D-Ala2-Met5-enkephalinamide (DALA) decreases the frequency of miniature, action potential-independent, spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) without causing a change in their amplitude. Thus, we conclude that DALA inhibits the action potential-independent release of GABA through a direct action on interneuronal synaptic terminals. In contrast, DALA reduces the amplitude of action potential-evoked, GABA-mediated IPSCs, as well as decreases their frequency. This suggests that the opioid-mediated inhibition of non-action potential-dependent GABA release reveals a mechanism that contributes to reducing action potential-evoked GABA release, thereby decreasing synaptic inhibition.

Action Potentials↗
PubMed1991

A requirement for the intercellular messenger nitric oxide in long-term potentiation.

Long-term potentiation (LTP) of synaptic transmission is a widely studied model of neuronal plasticity. The induction of LTP is known to require processes in the postsynaptic neuron, while experimental evidence suggests that the expression of LTP may occur in the presynaptic terminal. This has led to speculation that a retrograde messenger travels from the post- to the presynaptic cell during induction of LTP. Extracellular application or postsynaptic injection of two inhibitors of nitric oxide synthase, N-nitro-L-arginine or NG-methyl-L-arginine, blocks LTP. Extracellular application of hemoglobin, which binds nitric oxide, also attenuates LTP. These findings suggest that nitric oxide liberated from postsynaptic neurons may travel back to presynaptic terminals to cause LTP expression.

Amino Acid Oxidoreductases↗
PubMed1991

Synaptic localization of adrenergic disinhibition in the rat hippocampus.

Norepinephrine is an endogenous neurotransmitter that reduces synaptic inhibition onto pyramidal neurons in the hippocampus by an action at an alpha-adrenergic receptor. The physiological mechanism of this disinhibition was previously not known, except that it occurred at a site presynaptic to the inhibited pyramidal cell. In this paper we present evidence that adrenergic disinhibition is restricted to the early phase of the evoked inhibitory postsynaptic potential in area CA1 of the hippocampus. The locus of disinhibition does not appear to reside in the interneuronal terminal, axon, or cell body. Instead, adrenergic agonists appear to reduce evoked synaptic inhibition by depressing excitatory synapses that activate the interneuron.

Adrenergic alpha-Agonists↗
PubMed1991

LTP, post or pre? A look at the evidence for the locus of long-term potentiation.

It seems self-evident that changes in the cellular synaptic function of the brain must underlie the formation and storage of cognitive memories. Because it has been identified as a brain area important in the formation of memory, the hippocampus has been a focus in the study of such synaptic changes. An activity-induced increase in hippocampal synaptic efficacy, known as long-term potentiation (LTP), has been widely studied as a potential substrate for memory. This paper briefly reviews some of the significant progress that has been made in understanding the cellular mechanisms that underlie LTP, including recent experiments dealing with its synaptic locus, or the question of whether the mechanism regulating LTP is pre- or postsynaptic.

Animals↗
PubMed1988

Persistent protein kinase activity underlying long-term potentiation.

Long-term potentiation (LTP) of synaptic transmission in the hippocampus is a much-studied example of synaptic plasticity. Although the role of N-methyl-D-aspartate (NMDA) receptors in the induction of LTP is well established, the nature of the persistent signal underlying this synaptic enhancement is unclear. Involvement of protein phosphorylation in LTP has been widely proposed, with protein kinase C (PKC) and calcium-calmodulin kinase type II (CaMKII) as leading candidates. Here we test whether the persistent signal in LTP is an enduring phosphoester bond, a long-lived kinase activator, or a constitutively active protein kinase by using H-7, which inhibits activated protein kinases and sphingosine, which competes with activators of PKC (ref. 17) and CaMKII (ref. 18). H-7 suppressed established LTP, indicating that the synaptic potentiation is sustained by persistent protein kinase activity rather than a stably phosphorylated substrate. In contrast, sphingosine did not inhibit established LTP, although it was effective when applied before tetanic stimulation. This suggests that persistent kinase activity is not maintained by a long-lived activator, but is effectively constitutive. Surprisingly, the H-7 block of LTP was reversible; evidently, the kinase directly underlying LTP remains activated even though its catalytic activity is interrupted indicating that such kinase activity does not sustain itself simply through continual autophosphorylation (see refs 9, 13, 15).

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Norepinephrine decreases synaptic inhibition in the rat hippocampus.

The effects of norepinephrine (NE) on inhibitory synaptic potentials were studied on CA1 pyramidal neurons in the hippocampal slice in vitro. Norepinephrine caused the appearance of multiple population spikes in the CA1 region of the hippocampal slice, reminiscent of the actions of gamma-aminobutyric acid (GABA) antagonists. Intracellular recording revealed that NE causes a marked and reversible reduction in inhibitory postsynaptic potentials (IPSPs) recorded in CA1 pyramidal cells. This reduced IPSP results in a larger intracellular excitatory postsynaptic potential (EPSP), which can cause the cell to fire more than one action potential. This disinhibitory effect of NE appears to be mediated by an alpha-receptor, and occurs at a site presynaptic to the pyramidal cell, since NE does not change the reversal potential of the IPSP nor does it affect the amplitude or the reversal potential of iontophoretic GABA responses. In addition to reducing evoked IPSPs, NE causes an increase in the frequency of spontaneous IPSPs, suggesting that inhibition of interneuronal firing may not account for this disinhibitory action of NE.

Action Potentials↗
PubMed1988

Imaging of cytosolic Ca2+ transients arising from Ca2+ stores and Ca2+ channels in sympathetic neurons.

Changes in cytosolic free Ca2+ concentration [( Ca2+]i) due to Ca2+ entry or Ca2+ release from internal stores were spatially resolved by digital imaging with the Ca2+ indicator fura-2 in frog sympathetic neurons. Electrical stimulation evoked a rise in [Ca2+]i spreading radially from the periphery to the center of the soma. Elevated [K+]o also increased [Ca2+]i, but only in the presence of external Ca2+, indicating that Ca2+ influx through Ca2+ channels is the primary event in the depolarization response. Ca2+ release or uptake from caffeine-sensitive internal stores was able to amplify or attenuate the effects of Ca2+ influx, to generate continued oscillations in [Ca2+]i, and to persistently elevate [Ca2+]i above basal levels after the stores had been Ca2(+)-loaded.

Animals↗
PubMed1988

Spatial distribution of calcium channels and cytosolic calcium transients in growth cones and cell bodies of sympathetic neurons.

Ca2+ imaging and single-channel recording were used to study the regulation of cytosolic free Ca2+ ([Ca2+]i) in local regions of frog sympathetic neurons. Digital imaging with the fluorescent Ca2+ indicator fura-2 demonstrated: (i) resting [Ca2+]i of 70-100 nM; (ii) significant increases in [Ca2+]i in growth cones and cell bodies following depolarization induced by extracellular electrical stimulation or increased external K+; (iii) in cell bodies, large transient increases in [Ca2+]i following exposure to caffeine and sustained oscillations in [Ca2+]i in the presence of elevated K+ and caffeine; and (iv) in growth cones, smaller and briefer changes in [Ca2+]i in response to caffeine. The nature of the depolarization-induced Ca2+ entry was studied with cell-attached patch recordings (110 mM Ba2+ in recording pipette). Ca2+ channel activity was observed in 18 of 20 patches on cell bodies, 3 of 5 patches along neurites, and 36 of 41 patch recordings from growth cones. We observed two types of Ca2+ channels: L-type channels, characterized by a 28-pS slope conductance, sensitivity to dihydropyridine Ca2+ channel agonist, and availability even with depolarizing holding potentials; and N-type channels, characterized by a 15-pS slope conductance, resistance to dihydropyridines, and inactivation with depolarized holding potentials. Both types of channels were found on growth cones and along neurites as well as on cell bodies; channels often appeared concentrated in local hot spots, sometimes dominated by one channel type.

Action Potentials↗
PubMed1988

Enkephalin hyperpolarizes interneurones in the rat hippocampus.

1. Intracellular recordings were made from pyramidal cells and from electrophysiologically identified interneurones in the CA1 region of the hippocampal slice preparation from the rat. 2. Enkephalin blocked the hyperpolarization of pyramidal cells evoked by application of glutamate to synaptically coupled inhibitory interneurones. 3. Enkephalin hyperpolarized interneurones, most probably by increasing potassium conductance; this action was blocked by the opiate antagonist, naloxone. 4. Activation of gamma-aminobutyric acid(B) receptors with baclofen in interneurones produced a similar hyperpolarization that was resistant to naloxone. 5. In addition to hyperpolarizing interneurones, enkephalin blocked the inhibitory postsynaptic potential recorded in these cells. 6. These results suggest that opiate receptors are selectively localized on inhibitory interneurones in the hippocampus and are coupled to potassium channels. Activation of these receptors causes a disinhibition of both pyramidal cells and inhibitory interneurones.

Action Potentials↗
PubMed1987

Voltage clamp analysis of cholinergic action in the hippocampus.

A slow muscarinic EPSP, accompanied by an increase in membrane input resistance, can be elicited in hippocampal CA1 pyramidal cells in vitro by electrical stimulation of cholinergic afferents in the slice preparation. Associated with the slow EPSP is a blockade of calcium-activated potassium afterhyperpolarizations (AHPs) (Cole and Nicoll, 1984a). In this study a single-electrode voltage clamp was used to examine the currents affected by activation of muscarinic receptors, using either bath application of carbachol or electrical stimulation of the cholinergic afferents. The 3 main findings of this study are that (1) of the 2 calcium-activated potassium currents (termed IAHP and IC) in hippocampal pyramidal cells, only IAHP is sensitive to carbachol; (2) IAHP is approximately 10-fold more sensitive to carbachol than is another muscarine-sensitive current, IM; and (3) neither blockade of IAHP nor of IM can account for the production of the slow EPSP. Rather, the slow EPSP appears to be generated by the blockade of a nonvoltage-dependent, resting potassium current. We propose that the muscarinic blockade of IAHP, which largely accounts for spike frequency adaptation, is primarily involved in enhancing action potential discharge to depolarizing stimuli, while the slow EPSP acts directly to cause action potential discharge.

Acetylcholine↗
PubMed1986

Actions of noradrenaline recorded intracellularly in rat hippocampal CA1 pyramidal neurones, in vitro.

CA1 pyramidal neurones were studied in rat in vitro hippocampal slices using standard intracellular and single-electrode voltage-clamp recording techniques to examine the actions of noradrenaline (NA). NA had two different effects on the resting membrane potential of pyramidal neurones; either a hyperpolarization accompanied by a decrease in membrane input resistance, or less commonly, a depolarization accompanied by an increase in input resistance. In many cells, both effects, a hyperpolarization followed by a depolarization were observed. The depolarization was mediated by a noradrenergic beta-receptor. The hyperpolarization was more difficult to characterize, but may result from alpha-receptor activation. NA reduced the amplitude and duration of the slow calcium-activated potassium after-hyperpolarization (a.h.p.) that follows depolarization-induced action potentials. This action of NA was mediated by beta 1-noradrenergic receptors. NA, in the presence of tetrodotoxin and tetraethylammonium, reduced the a.h.p. without reducing the size of the calcium action potential which preceded it. This was unlike the action of the calcium channel blocker, cadmium, which reduced the calcium action potential and the a.h.p. in parallel. Furthermore, NA did not reduce the amplitude of calcium or barium currents recorded under voltage clamp after blockade of potassium currents. A functional consequence of this blockade of the calcium-activated a.h.p. was a reduction of the accommodation of action potential discharge such that the excitatory responses of the neurone to depolarizing stimuli, such as glutamate application or current passed through the recording electrode, were enhanced. We conclude that the effects of NA on calcium-activated potassium conductance and on resting membrane potential can interact to increase the signal-to-noise ratio of hippocampal pyramidal neurone responsiveness.

Action Potentials↗