Slow IPSP Research Articles

Slow synaptic inhibition in relation to frequency habituation in dentate granule cells of rat hippocampal slices.

In paired pulse stimulation experiments the mechanism underlying frequency habituation of postsynaptic potentials in dentate granule cells of rat hippocampal slices was studied by measuring extra- and intracellular potentials as well as changes in extracellular calcium [( ([Ca2+]0) and potassium concentrations ([K+]0). Orthodromic stimulation of the perforant path induced in most granule cells a late, slow hyperpolarization (SH), lasting for up to 1.2 s. During the SH the membrane conductance was increased by up to 40%. The reversal potential of the SH was around -90 mV and varied with the [K+]0. Frequency habituation was seen in all cells with the SH, whereas cells which display frequency potentiation had no SH. Lowering of [Ca2+]0 reversed paired pulse induced frequency habituation into frequency potentiation at [Ca2+]0 levels where the SH disappeared. Phaclofen blocked the SH and reversed frequency habituation into frequency potentiation. Elevating [Mg2+]0 also reversed frequency habituation into frequency potentiation and reduced the SH. We conclude that the SH represents a late, slow IPSP which is responsible for frequency habituation in dentate granule cells. We noted that during repetitive stimulation the SH soon started to fade. This effect can in part be attributed to extracellular K+-accumulation as suggested by the K+-dependence of the slow IPSP and the observations of changes in [K+]0 during repetitive stimulation. This could explain why frequency habituation reverses into frequency potentiation during repetitive stimulation.

Secondary late components of the muscarinic postsynaptic potentials, in rabbit superior cervical ganglion

The well known muscarinic slow excitatory polysynaptic potential (s-EPSP) of rabbit superior cervical ganglion (SCG) peaking at about 1–2 s and lasting 5–10 s, is immediately followed by an abrupt change in slope to a longer, lower depolarizing phase. A brief dip in the level of depolarization (DP) often separates the two depolarizing phases. The secondary phase of s-EPSP rises to its own peak at about 25 s; total duration 60–120 s. With repetition of orthodromic volleys secondary s-EPSP builds up more gradually than initial s-EPSP, but more rapidly than slow-slow (ss-) EPSP. The later ‘secondary’ depolarizing phase along with the antecedent ‘dip in DP’ are, like the ‘initial’ s-EPSP, eliminated by a muscarinic antagonist, quinuclinidyl benzilate hydrochloride (QNB). This distinguishes secondary s-EPSP from the even slower rising non-cholinergic ss-EPSP. The ss-EPSP, although relatively small in the responses to the usual 3-pulse test stimuli, rises to an extraordinary amplitude (equal to the compound action potential) during a 10 s–120 s train of pulses. Gallamine blocked most of the slow IPSP component in test responses but not initial or secondary s-EPSP. A preganglionic conditioning train (10/s for 2 min) induced a long-term-enhancement (LTE) of secondary s-EPSP lasting > 3 h, with maximum postconditioning percentage increases greater than for initial s-EPSP. Also enhanced was the dip in DP, now forming a deeper notch between initial and secondary s-EPSPs; this attains a maximum at about 30 min postconditioning but thereafter progressively loses the enhancement by about 90 min. The dip in DP appears to represent some delayed, perhaps hyperpolarizing process that may overlap with the initial and secondary phases of s-EPSP and affect their forms and peak amplitudes. This would not exclude the possibility that the initial and secondary phases of s-EPSP reflect multiple muscarinically activated electrogenic mechanisms having differing time-courses.

Pharmacological studies in frog sympathetic ganglion: support for the cholinergic monosynaptic hypothesis for slow IPSP mediation

The slow inhibitory postsynaptic potential (slow IPSP), the slow excitatory postsynaptic potential (slow EPSP), the late slow excitatory postsynaptic potential (late slow EPSP), and the fast excitatory postsynaptic potential/compound action potential (fast EPSP) were recorded from the 9th or 10th paravertebral sympathetic ganglia of bullfrogs (and some Rana pipiens frogs) by the sucrose-gap technique. The adrenergic antagonists phentolamine, dihydroergotamine and propranolol did not show any antagonistic effect on the slow IPSP when used at concentrations of up to 10, 100 and 10 μM, respectively. U-0521 (3′,4′-dihydroxy-2-methylpropriophenone, 50 μg/ml), a specific inhibitor of catechol- OM-methyltransferase, did not show any potentiating effect on the slow IPSP. The cholinesterase inhibitor neostigmine (0.5–1 μM) induced a large increase in the duration and amplitude of slow IPSP. When phentolamine and propranolol at concentrations greater than 10 μM were used the slow IPSP (and all other synaptic potentials) were non-specifically reduced in amplitude by these drugs. The results reported in this paper do not lend any support to the hypothesis that the slow IPSP in frog sympathetic ganglia is mediated by an adrenergic interneuron. The results are consistent with the proposal that the slow IPSP in this ganglion is mediated by a direct action of acetylcholine released from cholinergic preganglionic fibers.

Epileptogenic properties of the mast cell degranulating peptide in CA3 hippocampal neurones

The epileptogenic properties of the mast cell degranulating peptide (MCD) have been investigated in the CA3 region of the hippocampal slice preparation. Brief (3–5 min) bath application of MCD (0.5–2 μM) to CA3 hippocampal neurones produced an enhancement of the spontaneous synaptic activity and the appearance of spontaneous bursts that persisted for several hours. These bursts were network driven and the underlying paroxysmal depolarizing shift met the criteria for a giant excitatory postsynaptic potential (EPSP), with a reversal potential close to 0 mV. Furthermore following the application of MCD, stimulation of the mossy fibres, commissural or temporo-ammonic pathway evoked an EPSP followed by an evoked network burst. The bursts which could be elicited for several hours were reversibly blocked by a brief application of tetrodotoxin (TTX; 1μM) or cobalt (2 mM). In contrast, prior and concomitant treatment with TTX or cobalt prevented the occurrence of the bursts induced by MCD. The effects of MCD were not due to a blockade of GABAergic inhibition since the toxin did not reduce the fast and slow IPSP. Furthermore, the N- methyl- d-aspartate (NMDA) antagonists d-2-amino-phosphonovalerate (D-APV; 30 μM) or dl-amino-phosphoheptanoic acid (AP-7, 30 μM) did not block the action of MCD, suggesting that the activation of NMDA receptors are neither necessary nor sufficient for MCD-induced bursts. It is concluded that MCD induces in the CA3 region long-lasting changes in the synaptic responses which may be mediated through a presynaptic mechanism.

Noradrenaline mediates slow excitatory synaptic potentials in rat dorsal raphe neurons in vitro

Repetitive focal stimulation to the slice surface within the region of the dorsal raphe (DR) nucleus of rat brain elicited a slow excitatory synaptic potential (slow EPSP), which followed a slow inhibitory synaptic potential (slow IPSP) in a majority of the DR neurons. The slow EPSPs were associated with either an increase or a decrease in membrane resistance. Noradrenaline (NA) application caused a membrane depolarization in most of the DR neurons. The NA-induced depolarization was also accompanied by either an increase or a decrease in membrane resistance. Both the slow EPSP and NA-induced depolarization were inhibited by phentolamine and prazosin but not by yohimbine and propranolol. The result suggests that slow EPSPs in rat DR neurons are mediated by NA interacting with an α 1-adrenoceptor.

Evidence of slow IPSP in mammalian prevertebral ganglia

A short train of nerve stimulation evoked in a portion of neurons of the guinea pig inferior mesenteric ganglia a slow hyperpolarization (slow IPSP) which persisted when the preceding orthodromic spikes were reduced to subthreshold EPSPs by curare, was reversibly abolished in a low Ca solution, and was not blocked by atropine; furthermore, the post-tetanic hyperpolarization induced by direct intracellular stimulation was generally smaller than the slow IPSP evoked by nerve stimulation. The slow IPSP was often associated with a fall in membrane resistance and its amplitude decreased with membrane hyperpolarization. The results indicate that the slow hyperpolarization is a synaptic potential, and differs from the slow IPSP observed in mammalian and amphibian paravertebral ganglionic neurons in that it is atropine insensitive.

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 α 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.

Roles of cyclic nucleotides in the synaptic transmission in sympathetic ganglia of rabbits

1. Two kinds of slow postsynaptic potentials can be elicitable in the rabbit superior cervical ganglion: a dopaminergic hyperpolarizing (slow IPSP) one and a muscarinic depolarizing (slow EPSP) one, respectively. 2. Cyclic AMP may not be involved in the generation of slow IPSP, whereas it certainly mediates the dopamine-induced enduring modulatory enhancement of the slow EPSP response. 3. Cyclic GMP appears to mediate at least one of the components in the mechanism underlying the slow EPSP by generating a depolarization with no change in membrane conductance. 4. Cyclic GMP does additionally regulate the dopamine (or cyclic AMP)-induced modulatory enhancement of the slow EPSP by antagonizing it in a uniquely time-dependent fashion.

Slow inhibitory postsynaptic potentials and hyperpolarization evoked by noradrenaline in the neurones of mammalian sympathetic ganglion

Slow IPSPs evoked in the neurones of rabbit isolated superior cervical ganglion by repetitive orthodromic stimulation, and a response evoked in the neurones of this ganglion by perfusion of noradrenaline, were studied using intracellular microelectrodes. Slow IPSPs were observed in 36% of neurones studied, and when investigated after treatment with d-tubocurarine and neostigmine, had a mean amplitude of 4.4 ± 0.2 mV (mean ± S.E.) and duration of 5 sec to 1.5 min. Two types of slow IPSPs occurring in different neurones were found. The slow IPSP of the first type was followed by a decrease in cell input resistance, was increased by depolarization and decreased by hyperpolarization of the membrane, with the reversal potential, if estimated by extrapolation method, equal to −77.8 ± 3.3 mV. The slow IPSP of the second type was not followed by any change in cell input resistance, was increased by hyperpolarization and decreased by depolarization. The slow IPSP of the second type was reversibly blocked by phentolamine (1.4 × 10 −4 M). Noradrenaline (1 × 10 −4M) evoked hyperpolarization or hyperpolarization followed by depolarization in 55% of the neurones studied. Hyperpolarization evoked by noradrenaline had a mean amplitude of 5.0 ± 0.2 mV, was not followed by any change in cell input resistance, was reversibly blocked by phentolamine (1.4 × 10 −4 M), and was decreased by both depolarization and hyperpolarization of the cell membrane.

Roles of electrogenic Na + pump and K + conductance in the slow inhibitory postsynaptic potential of bullfrog sympathetic ganglion cells

The slow IPSP recorded from bullfrog sympathetic ganglion cells in the Ringer solution consists of two different potential components, namely ouabain-sensitive and ouabain-insensitive components. The present experimental analyses on these two potential components suggest that the former component is associated with an electrogenic Na + pump while the latter with an increase of K +-conductance. The slow IPSP recorded in K +-free solution is clearly mixed with a new potential component, which is not seen in the Ringer solution and differs from the usual slow IPSP. These results do not support the concept that the slow IPSP consists of the potential component associated with a fall of Na + conductance.

Postsynaptic modulation of excitatory process in sympathetic ganglia by cyclic AMP

THE principal neurones of the vertebrate sympathetic ganglia usually respond to suitable preganglionic stimuli with three types of temporally distinguishable postsynaptic potential (PSPs) in the following sequence: an initial excitatory one (fast EPSP), a slow inhibitory one (slow IPSP) and a slow excitatory one (slow EPSP)1,2. These three responses can also be distinguished pharmacologically: the fast EPSP is mediated by a nicotinic acetylcholine receptor, and the slow EPSP by a muscarinic acetylcholine receptor. The synaptic pathway of the slow IPSP includes intervening adrenergic cells (called “SIF” cells3) which release a catecholamine transmitter (identified as dopamine in the case of rabbbit4,5), in response to the muscarinic action of acetylcholine, and in turn hyperpolarise the ganglion cells.

Aplysia bursting neurons as endogenous oscillators. I. Phase-response curves for pulsed inhibitory synaptic input.

1. The left upper quadrant bursting neurons in the abdominal ganglion of Aplysia are isochronous, nonlinear oscillators. Transmembrane current and temperature are parameters of the bursting oscillator. 2. The phase-response curve (PRC) for pulsed inhibitory synaptic input from an interneuron describes the phase shift produced by synaptic input at different phases of the burst cycle. 3. The characteristic shape of the PRC consists of two linear functions that intersect at the point in the cycle where the burst of spikes ends. Whether the net effect of the synaptic input at a given phase is phase advance or phase delay depends on 1) the number of spikes inhibited, and 2) the duration of the inhibition relative to the duration of the free-run period. 4. The shape of the PRC remains constant when a stepwise change in a parameter is introduced, when the duration of the synaptic input is increased, when the fast component of the IPSP is blocked, and when a long hyperpolarizing pulse is used to mimic the slow IPSP. 5. The shape of the PRC is changed when short hyperpolarizing pulses or antidromic action potentials are used and when only the pacemaker oscillation is present in the bursting neuron. 6. Therefore, the synaptic modulation of the bursting rhythm is determined by the voltage change produced by the IPSP and its inhibition of spikes in the bursting neuron.

The SIF cell as a functional modulator of ganglionic transmission through the release of dopamine.

Acetylcholine (ACh), released from the preganglionic nerve terminal, has been well established as eliciting the excitatory postsynaptic potential (f-EPSP) by its nicotinic action on the sympathetic ganglion cell. The additional slow hyperpolarizing (inhibitory) and slow depolarizing (excitatory) postsynaptic potentials (s-IPSP and s-EPSP respectively) were later discovered. The schema for mediation of the slow PSPs was postulated: a muscarinic ACh action for the s-EPSP; and for the s-IPSP, an initial muscarinic ACh action on an adrenergic interneuron to release a catecholamine which in turn hyperpolarized principal ganglion cells. The above pathways are based on the findings that 1) the slow IPSP in particular is sensitive to α-adrenergic antagonists, 2) the low Ca/high Mg medium abolishes the hyperpolarizing (but not depolarizing) component present in the response of the ganglia to the muscarinic agents and 3) the putative catecholamine-transmitters can induce the appropriate hyperpolarzing membrane change. The recent histological studies, coupled with electrophysiological observation, on the newly discovered “SIF” cells have provided further support to the concept that such cells may actually play a functional role as the necessary predicted interneuron to mediate the s-IPSP. In the rabbit superior cervical ganglion, dopamine has been identified as the adrenergic transmitter contained in the SIF cells. Another possible role for the SIF cells is the mediation of the long-lasting modulatory (enhancing) effect on the s-EPSP; cyclic AMP, accumulated in the ganglion cells in response to dopamine action, appears to intracellularly mediate this effect.In the amphibian (frog) ganglia, the general feature for the mediation of the s-IPSP was found to be similar to that in the mammals (rabbit).

Unusual cholinergic response of bullfrog sympathetic ganglion cells.

The membrane of bullfrog sympathetic ganglion cells was hyperpolarized by a direct action of ACh (more than 0.5 mM) in a solution containing both nicotine (0.24 mM) and atropine (0.14 mM). This ACh hyperpolarization could be imitated by neither carbachol nor bethanechol, suggesting that the ACh hyperpolarization was the response which was produced by a specific action of ACh, which appeared to be neither nicotinic nor muscarinic. The size of ACh hyperpolarization was increased during a conditioning hyperpolarization. The ACh hyperpolarization was completely blocked by ouabain (2 times 10(-3) mM) and eliminated in the Na-free lithium solution. These aspects of the ACh hyperpolarization suggested that generation of this hyperpolarization was associated with the sodium pump. The ACh hyperpolarization seemed to be partially responsible for the production of the slow IPSP, since a part of the slow IPSP remained occasionally in the presence of both nicotine and atropine.

SOME ANALYSES OF THE SLOW INHIBITORY POSTSYNAPTIC POTENTIAL IN BULLFROG SYMPATHETIC GANGLIA

Experimental evidences indicating that the slow IPSP was produced from B cells in bullfrog sympathetic ganglia were presented. The slow IPSP was selectively depressed by the action of ouabain ; it, in comparison with the fast EPSP and slow EPSP in ganglionic B cells, was more sensitive to this drug. The muscarinic ACh-hyperpolarization, which corresponded to the slow IPSP, was also sensitive to ouabain. These results supported the hypothesis that the slow IPSP might be generated by an electrogenic sodium pump.

Slow inhibitory postsynaptic potentials of bullfrog sympathetic ganglia in sodium-free media

The LN potential (slow EPSP) of bullfrog sympathetic ganglia was restored while the P potential (slow IPSP) was not restored by perfusion with a sodium-free lithium or hydrazinium solution after a prolonged perfusion with a sodium-free sucrose solution. Similarly, the muscarinic ACh-depolarization was restored while the muscarinic ACh-hyperpolarization was not restored in a lithium or hydrazinium medium. These results support the hypothesis that the slow IPSP is produced by the activation of an electrogenic sodium pump.

A functional connection between postganglionic neurons in a bullfrog sympathetic ganglion

A tetanic antidromic stimulation of a group of ganglion cells in a nicotinized bullfrog sympathetic ganglion induced a slow and small hyperpolarization in the unstimulated, adjacent group of ganglion cells. Except for its enhancement by atropine, the hyperpolarization had a property essentially similar to that of the slow IPSP. In addition, the afterdischarge of the adjacent ganglion cells, which was elicited by preganglionic stimulation, in the presence of nicotine and atropine was suppressed at the time the hyperpolarization was generated in these neurons. The results indicate that the antidromic postganglionic volleys cause the liberation of a noncholinergic transmitter substance from the activated ganglion cells or possibly from some interneurons, and that the transmitter brings about in the unstimulated, neighboring ganglion cells a slow hyperpolarization which inhibits the generation of the after-discharge. Thus it is evident that a functional interrelation exists among the ganglion cells in a sympathetic ganglion.

Long latent periods and further analysis of slow synaptic responses in sympathetic ganglia.

Long latent periods and further analysis of slow synaptic responses in sympathetic ganglia.B LibetB LibetPublished Online:01 May 1967https://doi.org/10.1152/jn.1967.30.3.494MoreSectionsPDF (3 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByAmphibian sympathetic ganglia: An owner's and operator's manualProgress in Neurobiology, Vol. 43, No. 4-5Interaction of telenzepine with muscarinic receptors in mammalian sympathetic gangliaEuropean Journal of Pharmacology, Vol. 167, No. 1Secondary late components of the muscarinic postsynaptic potentials, in rabbit superior cervical ganglionJournal of the Autonomic Nervous System, Vol. 24, No. 1-2Significance of slow synaptic potentials for transmission of excitation in guinea-pig myenteric plexusNeuroscience, Vol. 14, No. 2Acetylcholine-induced electrical responses in neuroblastoma cellsNeuroscience, Vol. 8, No. 3Pharmacological properties and monoaminergic mediation of the slow IPSP, in mammalian sympathetic ganglionBrain Research, Vol. 242, No. 2Modulation of slow postsynaptic potentials by dopamine, in rabbit sympathetic ganglionBrain Research, Vol. 217, No. 1Biological activity of anti-brain antibodiesImmunology Letters, Vol. 1, No. 1Production of decremental oscillations following spike potential by muscarinic drugs, histamine and bradykinin in cat sympathetic ganglionNeuropharmacology, Vol. 18, No. 4Which postsynaptic action of dopamine is mediated by cyclic AMP?Life Sciences, Vol. 24, No. 12Synaptic events in sympathetic gangliaProgress in Neurobiology, Vol. 11, No. 2Identification of small intensely fluorescent (SIF) cells as chromaffin cells in bullfrog sympathetic gangliaBrain Research, Vol. 128, No. 2Criteria for distinguishing between monosynaptic and polysynaptic transmissionBrain Research, Vol. 105, No. 1Direct control of action potentials by acetylcholine in bullfrog sympathetic ganglion cellsBrain Research, Vol. 89, No. 1The role of muscarinic receptors in synaptic transmission and its modulation in the rabbit superior cervical ganglionEuropean Journal of Pharmacology, Vol. 29, No. 1Is inactivation of potassium conductance involved in slow postsynaptic excitation of sympathetic ganglion cells? Effects of nicotineLife Sciences, Vol. 14, No. 10Effects of excitation on the metabolism of a simple neuronal system: The mammalian sympathetic ganglionProgress in Neurobiology, Vol. 3The triphasic response of the isolated superior cervical ganglion of the rat to cholinergic stimulantsEuropean Journal of Pharmacology, Vol. 20, No. 1Cortical cellular activities during cyclically occurring inter-ictal epileptiform dischargesElectroencephalography and Clinical Neurophysiology, Vol. 31, No. 5Salivary secretory potentials in the marsupial Trichosurus vulpeculaComparative and General Pharmacology, Vol. 1, No. 3Synaptic organisation and other ultrastructural features of the superior cervical ganglion of the rat, kitten and rabbitMicron (1969), Vol. 2, No. 3Pharmacological studies on a cholinergic inhibition in the cerebral cortexBrain Research, Vol. 10, No. 3Acetylcholine-potential of sympathetic ganglion cell membraneLife Sciences, Vol. 7, No. 13An intracortical cholinergic inhibitory synapseLife Sciences, Vol. 7, No. 1 More from this issue > Volume 30Issue 3May 1967Pages 494-514 https://doi.org/10.1152/jn.1967.30.3.494PubMed6037590History Published online 1 May 1967 Published in print 1 May 1967 Metrics