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PubMed1996

Time course of inhibition induced by a putative saccadic suppression circuit in the dorsal lateral geniculate nucleus of the rabbit.

Psychological studies have revealed that a visual suppression occurs during the saccadic eye movements to maintain the stable visual image. This visual suppression is named saccadic suppression. A typical saccadic suppression precedes the saccadic eye movements by 30-60 ms, lasts 120-180 ms, and is followed by a 100-150 ms facilitation. Recently, we have revealed an inhibitory circuit connecting the deep layers of the superior colliculus (SC) to the dorsal lateral geniculate nucleus (LGN), via the central lateral nucleus in the thalamus (CL) and thalamic reticular nucleus (TRN). We speculated that this inhibitory circuit might mediate saccadic suppression in the rabbit. In the present study, we used intracellular recording technique to further examine the synaptic and intrinsic responses of CL cells, TRN cells, and LGN cells to the activation of this inhibitory circuit. We found that the stimulation of the deeper layers of the SC induced a fast excitation post-synaptic potential (EPSP) in CL cells, followed by a robust EPSP in TRN cells and a prolonged inhibitory postsynaptic potential (IPSP) in LGN cells. The EPSP in TRN cells was always followed by a small inhibitory postsynaptic potential (IPSP). The IPSP in LGN cells lasted about 133 +/- 27 ms. Sometimes, a rebound bursting occurred after the IPSP in LGN cells. We also examined whether activation of this inhibitory circuit could suppress the retino-geniculo-cortical pathway. We found that the SC stimulation always suppressed the evoked potential in the visual cortex induced by the stimulation of the optic chiasm. Our results of the inhibitory circuit can induce an inhibition in the LGN and a suppression on the retino-geniculo-cortical pathway. The time courses of the inhibition and suppression were compatible with that of saccadic suppression revealed by psychological and physiological studies. These results support the idea that the inhibitory circuit of SC (deeper layers)-CL-TRN-LGN may mediate the saccadic suppression in the rabbit LGN.

Animals↗

PubMed2001

High-affinity zinc potentiation of inhibitory postsynaptic glycinergic currents in the zebrafish hindbrain.

Zinc has been reported to potentiate glycine receptors (GlyR), but the physiological significance of this observation has been put in doubt by the relatively high values of the EC(50), 0.5-1 microM, since such concentrations may not be attained in the synaptic cleft of glycinergic synapses. We have re-evaluated this observation in the frame of the hypothesis that contaminant heavy metals present in usual solutions may have lead to underestimate the affinity of the zinc binding site, and therefore to underestimate the potential physiological role of zinc. Using chelators either to complex heavy metals or to apply zinc at controlled concentrations, we have examined the action of zinc on GlyR kinetics in outside-out patches from 50-h-old zebrafish Mauthner cells. Chelating contaminating heavy metals with tricine or N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN) decreased the duration of the currents evoked by glycine, confirming that traces of heavy metals alter the GlyR response in control conditions. Using tricine- (10 mM) buffered zinc solution, we then showed that zinc increases the amplitude of outside-out responses evoked by 0.1-0.5 mM glycine with an EC(50) of 15 nM. In contrast zinc had no effect on the amplitude of currents evoked by a saturating concentration (3-10 mM) of glycine. This suggests that zinc enhances GlyR apparent affinity for glycine. The study of the effects of zinc on the kinetics of the response indicates that this increase of apparent affinity is due to a decrease of the glycine dissociation rate constant. We then analyzed the effects of zinc on postsynaptic GlyRs in whole cell recordings of glycinergic miniature inhibitory postsynaptic currents (mIPSCs). Chelation of contaminant heavy metals decreased the amplitude and the duration of the mIPSCs; inverse effects were observed by adding zinc in buffered solutions containing nanomolar free zinc concentrations. Zinc plus tricine or tricine alone did not change the coefficient of variation ( approximately 0.85) of the mIPSC amplitude distributions. These results suggest that postsynaptic GlyRs are not saturated after the release of one vesicle.

Animals↗

PubMed1992

Halothane-induced hyperpolarization and depression of postsynaptic potentials of guinea pig thalamic neurons in vitro.

Intralaminar thalamic nuclei have been considered to be a component of the non-specific sensory system which is involved in physiological functions related to consciousness and pain sensation. The effect of halothane on membrane potentials and synaptic properties of neurons of the parafascicular (Pf) nucleus in guinea pig brain slices was investigated using intracellular recording methods. Halothane at concentrations of 0.4-1.0 mM, which are in the range of clinical concentrations, produced hyperpolarizations of 2-8 mV in approximately 50% of the cells. The halothane-induced hyperpolarization was nullified at a membrane potential close to the K+ equilibrium potential. The amplitude of the hyperpolarization was dependent on the external K+ concentration, and was decreased by either Ba2+, or 4-aminopyridine, or intracellular injection of Cs+. All these results indicate that the hyperpolarization was due to an increase in K+ conductance. Halothane at clinical concentrations depressed both excitatory and inhibitory postsynaptic potentials in a concentration-dependent manner. On the other hand hyperpolarizing responses to exogenous gamma-aminobutyric acid (GABA) in the presence of bicuculline were suppressed by halothane, but depolarizing responses to L-glutamate were not altered. The results indicate that the depressant action of the anesthetic on the excitatory postsynaptic potential (EPSP) may occur presynaptically, whereas the blocking action on the inhibitory postsynaptic potential (IPSP) may occur postsynaptically.

Animals↗

PubMed1994

Lesion-induced transient suppression of inhibitory function in rat neocortex in vitro.

The structural and functional consequences of a local thermolesion were examined in rat neocortex with electrophysiological in vitro techniques and immunocytochemistry. Age-matched untreated and sham-operated animals served as controls and were analysed in the same way. The lesions consisted of a core of coagulated tissue 2-3 mm in diameter and reached ventrally into the deep cortical layers. After two days reactive astrocytes and after nine days a dense gliosis were observed in the immediate vicinity. Modifications in the intrinsic membrane characteristics and the synaptic network properties were investigated with intra- and extracellular recording techniques after survival times of one to eight days. Neurons recorded in the surrounding of lesions in neocortical slices revealed a significantly more depolarized resting membrane potential and a higher neuronal input resistance. In comparison to cells in control slices, maximal discharge rates to injection of depolarizing current pulses of neurons close to a focal lesion were not significantly altered and intrinsic burst firing was never observed. However, between postlesion days 1 and 5, neurons in the surroundings of lesions showed a transient increase in synaptic excitability. This hyperactivity was most clearly pronounced at a distance of 2-3 mm from the centre of the lesion (i.e. about 1-1.5 mm away from the lesion border) and characterized by long-duration field potential responses and multiphasic long-lasting excitatory postsynaptic potentials to orthodromic stimulation of the afferent input. This lesion-induced hyperexcitability was associated with a significant reduction in the peak conductance of the Cl(-)-dependent fast inhibitory postsynaptic potential and the K(+)-dependent long-latency inhibitory postsynaptic potential, suggesting that the intracortical GABAergic system was functionally impaired. The decrease in synaptic inhibition was associated with prolonged N-methyl-D-aspartate receptor-mediated activity, which could be reversibly blocked by D-amino-phosphonovaleric acid. In addition, neurons recorded in the vicinity of the lesion responded to an orthodromic synaptic stimulus with a long-lasting burst. The lesion-induced disturbance in the balance between the excitatory and inhibitory system may not only have profound influences on the mechanisms of intracortical information processing, but may also lead to the expression of epileptiform activity and long-term functional deficits.

Action Potentials↗

PubMed1987

Motoneuron properties during motor inhibition produced by microinjection of carbachol into the pontine reticular formation of the decerebrate cat.

It is well established that cholinergic agonists, when injected into the pontine reticular formation in cats, produce a generalized suppression of motor activity (1, 3, 6, 14, 18, 27, 33, 50). The responsible neuronal mechanisms were explored by measuring ventral root activity, the amplitude of the Ia-monosynaptic reflex, and the basic electrophysiological properties of hindlimb motoneurons before and after carbachol was microinjected into the pontine reticular formation of decerebrate cats. Intrapontine microinjections of carbachol (0.25-1.0 microliter, 16 mg/ml) resulted in the tonic suppression of ventral root activity and a decrease in the amplitude of the Ia-monosynaptic reflex. An analysis of intracellular records from lumbar motoneurons during the suppression of motor activity induced by carbachol revealed a considerable decrease in input resistance and membrane time constant as well as a reduction in motoneuron excitability, as evidenced by a nearly twofold increase in rheobase. Discrete inhibitory postsynaptic potentials were also observed following carbachol administration. The changes in motoneuron properties (rheobase, input resistance, and membrane time constant), as well as the development of discrete inhibitory postsynaptic potentials, indicate that spinal cord motoneurons were postsynaptically inhibited following the pontine administration of carbachol. In addition, the inhibitory processes that arose after carbachol administration in the decerebrate cat were remarkably similar to those that are present during active sleep in the chronic cat. These findings suggest that the microinjection of carbachol into the pontine reticular formation activates the same brain stem-spinal cord system that is responsible for the postsynaptic inhibition of alpha-motoneurons that occurs during active sleep.

Action Potentials↗

PubMed1986

Postsynaptic-GABAergic inhibition of non-pyramidal neurons in the guinea-pig hippocampus.

Intracellular recording and staining was applied to study non-pyramidal neurons in the guinea-pig hippocampus. To avoid accidental impalement of pyramidal or granule cells, two hippocampal regions known to be devoid of pyramidal or granule cells were chosen. In transverse and longitudinal slices, neurons of the deep hilar region (zone 4 of Amaral3), and in transverse slices, neurons of the stratum lacunosum-moleculare (CA3) were impaled. The intracellular staining with Lucifer Yellow revealed that of 20 neurons stained in these zones all were non-pyramidal neurons. Hilar neurons, situated just below the granular layer, differed from granule cells and CA3 neurons with respect to their action potential waveform and their current/voltage relationship. In contrast to granule cells, hilar neurons exhibited spontaneous bursts in the presence of bicuculline (25 microM). In all neurons impaled in the hilar region and the stratum lacunosum-moleculare (n = 42), inhibitory postsynaptic potentials could be elicited. These inhibitory postsynaptic potentials were blocked by bicuculline. In transverse slices, perforant path stimulation elicited inhibition preceding excitation in hilar neurons and excitation preceding inhibition in granule cells. Since non-pyramidal neurons are likely to be inhibitory neurons, our data suggest that GABAergic neurons in the hilus or in the stratum lacunosum-moleculare are controlled by inhibitory GABAergic synapses. This was verified by immunocytochemistry using antibodies against glutamate decarboxylase, the gamma-aminobutyric acid synthetizing enzyme. In both hippocampal regions studied, glutamate decarboxylase-positive synaptic terminals on glutamate decarboxylase-positive cells were observed. It is concluded that disinhibition is an important feature of information processing in the hippocampus, and that disinhibition is mediated by GABAergic synapses on GABAergic neurons.

Action Potentials↗

PubMed1995

GABAergic inhibitory inputs to subfornical organ neurons in rat slice preparations.

To investigate GABAergic inhibitory inputs to neurons of the subfornical organ (SFO), intracellular recordings were made in rat brain slice preparations. Inhibitory postsynaptic potentials, which occurred spontaneously or were evoked by focal electric stimulation, had reversal potentials of approximately -60 mV, and were almost totally abolished by the GABAA antagonists bicuculline at 3-100 microM or picrotoxin at 50 microM. Following the application of bicuculline or picrotoxin, the resting membrane potentials were decreased by 4-8 mV. GABA at 10-100 microM and the GABAA agonist muscimol at 1-100 microM decreased the membrane resistance and the firing rate in all neurons tested. The reversal potential of the response to muscimol was similar to that for inhibitory postsynaptic potentials. The actions of muscimol persisted in the presence of 1 microM tetrodotoxin, implying that muscimol must act directly on the recorded neurons. These results suggest that there is a tonic inhibitory GABAergic input to SFO neurons which are mainly mediated through GABAA receptors.

Animals↗

PubMed1997

Presynaptic and postsynaptic GABAB receptors of neocortical neurons of the rat in vitro: differences in pharmacology and ionic mechanisms.

The properties of pre- and postsynaptic GABAB receptors were investigated with intracellular recordings from rat neocortical neurons in vitro. An antagonist of the GABAB receptor (CGP 35348) and ions or drugs interfering with GABAB receptor-mediated K+ conductance (Ba2+, QX 314) were employed to delineate possible differences. CGP 35348 reduced the conductance of the late inhibitory postsynaptic potential (IPSPB) in a dose-dependent manner. Neither the early GABAA receptor-mediated inhibitory postsynaptic potential (IPSPA), nor resting membrane potential or direct excitability, were consistently affected by CGP 35348. Bath application of 100 mumol/l Ba2+ decreased IPSPB conductance to about 40% and increased IPSPA conductance to 130% of control. The depression of a second IPSP by a pair of stimuli (paired pulse depression, or PPD) was used as an index for presynaptic GABAB receptor activation. Neither CGP 35348 nor Ba2+ exerted significant effects on the PPD at intervals of 400 msec. The dependence of PPD on the latency of the interval of the stimulus pair was investigated after intracellular applicatio of QX 314 had virtually abolished the IPSPB. Decreasing the stimulus interval from 500 msec to 100 msec revealed a stronger depression of the second IPSPA. Application of CGP 35348 alleviated PPD for stimulus intervals below 300 msec. The data indicate a distinct pharmacological difference between pre- and postsynaptic GABAB receptors. Moreover, we suggest that two temporally distinct presynaptic GABAB receptor effects contribute to PPD: a short-lasting effect, sensitive to CGP 35348, and a long-lasting effect, insensitive to CGP 35348. The latter is insensitive to Ba2+, implying that this component is not associated with a K+ conductance mechanism.

Animals↗

PubMed1992

Sensitization of locus ceruleus neurons during withdrawal from chronic stimulants and antidepressants.

The effects of chronic exposure to cocaine, amphetamine and desipramine on noradrenergic neurons in the locus ceruleus were examined using intracellular recordings in rat brain slices. Animals were treated for 2 weeks with either cocaine, amphetamine or desipramine, and all recordings were made after a 1-week withdrawal period. Cells from all three drug-treated groups showed a significant increase in sensitivity to the acute effects of cocaine and amphetamine in prolonging the time course of the noradrenaline-mediated inhibitory postsynaptic potential. At the highest cocaine and amphetamine doses tested (10 and 3 microM, respectively), the inhibitory postsynaptic potential duration was increased approximately 233% in the drug-treated groups relative to saline controls. In addition, locus ceruleus neurons from the cocaine-, amphetamine- and desipramine-treated groups showed a significant 10, 12 and 17% increase, respectively, in the maximum outward current produced by clonidine. There was also a significant increase in the behavioral sensitivity of the drug-treated animals to the sedative effects of clonidine. The mechanisms responsible for the increased sensitivity to the acute effects of cocaine, amphetamine and alpha-2 agonists may play a role in the withdrawal response to psychostimulants.

Amphetamine↗

PubMed1982

Multiple actions of acetylcholine on hippocampal pyramidal cells in organotypic explant cultures.

Hippocampal cultures were prepared from 7- to 10-day-old rats by means of the roller-type technique. The preservation of the characteristic hippocampal cytoarchitecture allowed, after many weeks in vitro, impalement of pyramidal cells by microelectrodes under visual control. Application of 10(-7) to 10(-5) M acetylcholine to the bath depolarized hippocampal pyramidal cells, strongly increased their rate of firing and induced paroxysmal depolarization shifts. This depolarizing action was accompanied by a reduction in the amplitude of evoked postsynaptic potentials. Whereas it was not clear whether the decrease in the amplitude of the excitatory postsynaptic potentials was only a result of membrane depolarization, acetylcholine clearly and reversibly reduced the potency of evoked inhibitory postsynaptic potentials. Iontophoresis of acetylcholine to the perisomatic region of pyramidal neurons, like acetylcholine applied to the bath, increased their firing rate and powerfully decreased the amplitude and duration of spontaneous and evoked inhibitory postsynaptic potentials. In contrast, iontophoresis of acetylcholine in the pyramidal cell layer at a distance from the recorded neuron generated a hyperpolarizing response associated with a reduction in firing rate. At high current strength, the initial hyperpolarization was (often) followed by a paroxysmal depolarization shift. High frequency electrical stimulation with electrodes located close to the acetylcholine pipette in the pyramidal cell layer (i.e. about 1 mm away from the recorded neuron) mimicked the acetylcholine effect. Resistance measurements indicated that membrane input resistance was decreased in the majority of cells during application of acetylcholine. This decrease in membrane resistance may result from a direct action of acetylcholine or from an increased synaptic activity. Synaptic alterations induced by acetylcholine were quick in onset and in recovery, while the increase in the rate of firing occurred somewhat later. Atropine (10(-5) M), which had no significant action by itself, completely abolished the action of acetylcholine applied to the bath or by iontophoresis. In contradistinction, naloxone did not influence the acetylcholine effects, although opiates and opioid peptides produce paroxysmal depolarization shifts in pyramidal cells which resemble those induced by acetylcholine. Addition of 8-16 mM magnesium to the bathing solution or exposure of the cultures to a calcium-free solution containing 1 mM cobalt abolished the effects of acetylcholine. In the presence of 10(-6) g/ml tetrodotoxin, 10(-5) M acetylcholine decreased the membrane input resistance of pyramidal cells, reduced their threshold for the generation of tetrodotoxin-resistant spikes and generated paroxysmal depolarization shifts in a proportion of pyramidal cells...

Acetylcholine↗

PubMed1996

Shared calcium signaling pathways in the induction of long-term potentiation and synaptic disinhibition in CA1 pyramidal cell dendrites.

1. Calcium signaling pathways were examined in the induction of long-term synaptic disinhibition following tetanization. Effects of tetanization on gamma-aminobutyric acid-A (GABAA receptor-mediated inhibitory responses were measured and compared with excitatory responses under experimental conditions previously used for examining induction mechanisms of N-methyl-D-aspartate (NMDA)-dependent long-term potentiation (LTP). Intracellular recordings were performed in current-clamp and discontinuous single-electrode voltage-clamp (dSEVC) modes in CA1 pyramidal cell apical dendrites in hippocampal slices of adult guinea pigs with the use of sharp electrodes. Test pulses and tetanic stimuli were applied to the Schaffer collateral fibers in stratum radiatum. 2. Under standard control conditions [3 M K Ac in the recording pipette and artificial cerebrospinal fluid as extracellular solution], tetanization-induced sustained increases of excitatory responses were accompanied by marked decreases of parameters of GABAA-mediated synaptic inhibition: at 40 min after tetanization [posttetanus 40 (PT 40)], orthodromically evoked excitatory postsynaptic potential (EPSP) peak amplitudes were on average 195 +/- 15% (mean +/- SE) and excitatory postsynaptic currents (IPSPs) were 166 +/- 10% of pretetanus controls. Peak amplitudes of orthodromically evoked inhibitory postsynaptic potentials (IPSPs) were 30 +/- 5% and inhibitory postsynaptic currents (IPSCs) were 21 +/- 4% at PT 40. Synaptic GABAA conductances (measured as chord conductances) were reduced to 22 +/- 4% at PT 40. Iontophoretic GABAA responses measured as conductance changes were 28 +/- 4% of pretetanus controls at PT 40. 3. A role of NMDA receptors in induction of long-term synaptic disinhibition was tested by preventing NMDA receptor activation 1) by pharmacological means and 2) by holding the membrane clamped at -80 mV (in dSEVC) during tetanization. In the presence of the NMDA-receptor antagonist D-2-amino5-phosphonopentanoic acid (D-AP5) 10-40 microM), orthodromically evoked EPSP amplitudes were 107 +/- 9%, EPSCs were 104 +/- 6%, GABAA-mediated IPSPs were 88 +/- 8%, IPSCs were 97 +/- 8%, synaptic GABAA conductances were 84 +/- 9%, and iontophoretic GABAA conductances were 102 +/- 13% at PT 40. In recordings in which the dendritic membrane potential was clamped at -80 mV during tetanization, orthodromically evoked peak amplitudes of EPSPs were 105 +/- 11%, EPSCs were 102 +/- 8, IPSPs were 103 +/- 4%, IPSCs were 102 +/- 5%, GABAA chord conductances were 101 +/- 9%, and iontophoretically evoked GABAA conductances were 105 +/- 5% at PT 40. 4. In recordings in which the intracellular pipette was preloaded with the Ca2+ chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N'N"-tetraacetic acid (BAPTA) (5mM), long-term changes of synaptic transmission (increases of excitation, decreases of synaptic inhibition) were prevented. At PT 40, EPSP peak amplitudes were 93 +/- 7%, EPSCs were 115 +/- 6%, IPSPs were 115 +/- 9%, IPSCs were 117 +/- 8%, and synaptic GABAA conductances were 108 +/- 17%. Iontophoretic conductances at PT 40 were 109 +/- 9% over pretetanus controls when recorded with BAPTA-containing electrodes. 5. In recordings in which the intracellular pipette was preloaded with cypermethrin, a potent and selective inhibitor of phosphatase 2B, respective long-term changes of synaptic transmission (increases of excitation, decreases of synaptic inhibition) were prevented. At PT 40, EPSP peak amplitudes were 98 +/- 6%, EPSCs were 105 +/- 10%, IPSPs were 99 +/- 5%, IPSCs were 104 +/- 7%, synaptic GABAA conductances were 97 +/- 6% and iontophoretic GABAA conductances were 113 +/- 18% over pretetanus controls in cypermethrin-containing recordings. 6. In conclusion, the data presented demonstrate shared cellular pathways in the induction of both LTP and long-term synaptic disinhibition in apical dendrites of CA1 pyramidal cells after tetanization of the Schaffer collaterals.

Animals↗

PubMed1985

gamma-Aminobutyrate sensitivity does not change during long-term potentiation in rat hippocampal slices.

Long-term potentiation is a long-lasting enhancement of synaptic efficacy following brief, high-frequency, repetitive stimulation of a monosynaptic input. Intracellular recordings have shown that the inhibitory postsynaptic potential changes in amplitude during long-term potentiation. Yet how this may occur is unclear. To test for a possible alteration in postsynaptic sensitivity to the recurrent inhibitory transmitter gamma-aminobutyrate, we have examined the effect of gamma-aminobutyrate, focally applied to the hippocampal CA1 cell-body layer, on the extracellular recorded action potential (population spike). We found that the degree, duration, dose-dependence and time-course of inhibition produced by gamma-aminobutyrate are unchanged during long-term potentiation. This suggests that a change in sensitivity of CA1 pyramidal cells to the transmitter gamma-aminobutyrate is not the reason for the alteration in the inhibitory postsynaptic potential during long-term potentiation.

Animals↗

PubMed1989

Corollary discharge inhibition and preservation of temporal information in a sensory nucleus of mormyrid electric fish.

Knollenorgan electroreceptors in mormyrid fish are concerned with electrocommunication, i.e., with detecting electric organ discharges (EODs) of other electric fish. But knollenorgan electroreceptors are also activated by the fish's own EOD. Potential interference by such self-stimulation is blocked by an inhibitory corollary discharge in the nucleus of the electrosensory lateral line lobe (NELL), the first central relay of the knollenorgan pathway. This study used intracellular recording and staining to examine the mechanism of the corollary inhibition and the specializations in anatomy and physiology that permit the accurate relaying of temporal information about the EODs of other fish. Several events are recorded inside primary knollenorgan afferents in addition to a large orthodromic action potential. The additional events include small orthodromic electronic epsps, postsynaptic action potentials, and a corollary discharge inhibitory postsynaptic potential (ipsp) associated with the EOD motor command. These additional events are also recorded in NELL cells and almost certainly originate there. Electrical coupling between afferents and cells makes it possible to observe the events inside primary afferents. The corollary discharge ipsp in the cell is associated with a conductance increase and inverts rapidly when recorded with chloride-containing electrodes, supporting a hypothesis of GABA mediation. The ipsp lasts longer in cells than in afferents. Each electrotonic excitatory postsynaptic potential (epsp) is probably caused by a single primary afferent, and any one of several epsps in a given cell seems capable of eliciting a postsynaptic spike in that cell. The epsps follow stimulation rates as high as 500/sec with minimal variability. No lateral inhibition is observed in NELL. These and other properties indicate that the knollenorgan pathway is specialized for temporal information rather than spatial or intensity information.

Action Potentials↗

PubMed2000

Clostridium difficile toxin A excites enteric neurones and suppresses sympathetic neurotransmission in the guinea pig.

BACKGROUND AND AIMS: Evidence suggests that the intestinal actions of Clostridium difficile toxin A-stimulation of secretion and motility, and an acute inflammatory response-have a neurally mediated component. METHODS: Direct intracellular electrophysiological recording of electrical and synaptic behaviour in enteric neurones was performed in the submucous plexus of guinea pig small intestine during exposure to the toxin. RESULTS: Application of toxin A affected both the electrical behaviour of the neuronal cell bodies and inhibitory noradrenergic neurotransmission to the cell bodies. Altered electrical behaviour included depolarisation and increased excitability. Tetrodotoxin or a histamine H(2) receptor antagonist did not affect the depolarisation evoked by toxin A. Failure of the histamine antagonist to suppress the actions of toxin A is evidence that its actions were not mediated by degranulation of intramural mast cells. The action of toxin A on neurotransmission was suppression of inhibitory postsynaptic potentials evoked in the neuronal cell bodies by stimulation of sympathetic nerve fibres that synapsed with the cell bodies. The inhibitory postsynaptic potentials were mediated by norepinephrine (noradrenaline) acting at postsynaptic alpha adrenoceptors on the cell bodies. Hyperpolarising responses evoked in the cell bodies by micropressure application of norepinephrine were unaffected by toxin A. This fulfils criteria for a presynaptic inhibitory action of toxin A to suppress release of norepinephrine from sympathetic postganglionic axons. CONCLUSIONS: Results suggest that the neural component of the action of toxin A involves both direct excitation of enteric neurones and suppression of norepinephrine release from postganglionic sympathetic nerve fibres in the enteric nervous system.

Animals↗

PubMed1999

Ultra-slow oscillation (0.025 Hz) triggers hippocampal afterdischarges in Wistar rats.

Oscillations in neuronal networks are assumed to serve various physiological functions, from coordination of motor patterns to perceptual binding of sensory information. Here, we describe an ultra-slow oscillation (0.025 Hz) in the hippocampus. Extracellular and intracellular activity was recorded from the CA1 and subicular regions in rats of the Wistar and Sprague-Dawley strains, anesthetized with urethane. In a subgroup of Wistar rats (23%), spontaneous afterdischarges (4.7+/-1.6 s) occurred regularly at 40.8+/-15.7 s. The afterdischarge was initiated by a fast increase of population synchrony (100-250 Hz oscillation; "tonic" phase), followed by large-amplitude rhythmic waves and associated action potentials at gamma and beta frequency (15-50 Hz; "clonic" phase). The afterdischarges were bilaterally synchronous and terminated relatively abruptly without post-ictal depression. Single-pulse stimulation of the commissural input could trigger afterdischarges, but only at times when they were about to occur. Commissural stimulation evoked inhibitory postsynaptic potentials in pyramidal cells. However, when the stimulus triggered an afterdischarge, the inhibitory postsynaptic potential was absent and the cells remained depolarized during most of the afterdischarge. Afterdischarges were not observed in the Sprague-Dawley rats. Long-term analysis of interneuronal activity in intact, drug-free rats also revealed periodic excitability changes in the hippocampal network at 0.025 Hz. These findings indicate the presence of an ultra-slow oscillation in the hippocampal formation. The ultra-slow clock induced afterdischarges in susceptible animals. We hypothesize that a transient failure of GABAergic inhibition in a subset of Wistar rats is responsible for the emergence of epileptiform patterns.

Animals↗

PubMed1990

Mechanisms of depolarizing inhibition at the crayfish giant motor synapse. II. Quantitative reconstruction.

1. The relative strengths of four mechanisms of depolarizing synaptic inhibition described in the previous paper were evaluated with an electrical model of the giant motor synapse (GMS) and postsynaptic region of the motor giant motoneuron (MoG). 2. The model consists of one compartment that represents the presynaptic region of the medial giant (MG) interneuron and three compartments that represent the postsynaptic region and proximal axon of the MoG. The presynaptic MG compartment is linked to a postsynaptic MoG compartment by a rectifying conductance that represents the GMS. Each compartment consists of parallel paths to ground for active and/or passive membrane currents. 3. Parameter values of the model were set so the MG compartment would replicate an MG impulse and the MoG compartments would replicate the current-clamp, voltage-clamp, and synaptic responses of a single MoG neuron described in the previous paper. The Hodgkin-Huxley equations described voltage-sensitive sodium and potassium currents. 4. Comparison of the MoG compartment currents that mediate an inhibited excitatory postsynaptic potential (EPSP) [triggered during a depolarizing inhibitory postsynaptic potential (d-IPSP)] with those of an uninhibited EPSP indicate that all four mechanisms have significant inhibitory effects. Reverse bias of the GMS by the d-IPSP reduced the GMS current by 65 nA (12%). The remaining inward current was further reduced by a 243-nA outward current through the inhibitory postsynaptic conductance. The d-IPSP inactivated sodium conductance so the inward sodium current evoked by the EPSP was reduced by 319 nA (-68%). The d-IPSP reduced the latency for potassium activation by the EPSP so that the outward potassium current coincided with the inward sodium current and reduced the net inward current by 100 nA. Together, these mechanisms reduced the EPSP amplitude by 69%. 5. The resting potential of MoG is normally 15 mV more positive than MG rest potential, but in some preparations this difference may be as much as 25 mV or as little as 0 mV. Corresponding differences in the rest potentials of the MoG and MG models have little effect on the amplitude of the model MoG EPSP because changes in the inward synaptic and sodium currents are balanced by corresponding changes in the outward potassium current.

Animals↗

PubMed1977

Effects of strychnine, bicuculline, and picrotoxin on inhibition of hypoglossal motoneurons.

Postsynaptic potentials, evoked by lingual or hypoglossal nerve stimulation, were recorded from hypoglossal motoneurons of the cat with glass microelectrodes. Lingual nerve-evoked inhibitory postsynaptic potentials (LIPSPs) were recorded in 98% of hypoglossal motoneurons. Hypoglossal nerve stimulation caused a hyperpolarizing potential following the antidromic spike in all hypoglossal motoneurons tested. This potential was unaffected by depolarizing or hyperpolarizing currents, could not be evoked at a stimulus strength less than that which was threshold for the antidromic action potential, and did not change in shape or amplitude at stimulus strengths which were above threshold for antidromic invasion. This hyperpolarizing potential was therefore considered to be an afterhyperpolarization. However, hypoglossal nerve-induced inhibitory postsynaptic potentials were recorded from hypoglossal units which had characteristics of interneurons, thus suggesting the presence of afferent fibers in the hypoglossal nerve. The hypoglossal nerve-induced afterhyperpolarization was not affected by strychnine, bicuculline, or picrotoxin. The LIPSP was antagonized by strychnine but unaffected by bicuculline or picrotoxin. The results suggest that inhibition of hypoglossal motoneurons via the lingual nerve is more likely to be mediated by glycine than gamma-aminobutyric acid (GABA) and is therefore similar to the strychnine-sensitive postsynaptic inhibition of spinal motoneurons.

Animals↗

PubMed1989

The effects of brainstem peribrachial stimulation on neurons of the lateral geniculate nucleus.

The intracellular effects of brainstem peribrachial stimulation on lateral geniculate neurons were investigated in the cat. Experiments were performed in cats under barbiturate or urethane anaesthesia and in non-anaesthetized deafferented animals. Most animals were pretreated with reserpine and were acutely deprived of their retinal and visual cortical inputs. Short trains of stimuli triggered a transient depolarization in most relay neurons (latency: 20-30 ms; duration: 200-300 ms). This depolarization could be interrupted by a short-duration unitary inhibitory postsynaptic potential. The depolarization increased with membrane hyperpolarization and was associated with an increase in membrane conductance. The inhibitory postsynaptic potential had an intrathalamic origin and likely resulted from parallel activation of intrageniculate interneurons. The above responses were largely enhanced in reserpinized cats and were completely abolished by small doses of barbiturates. Iontophoretic applications of the nicotinic blocker, hexamethonium, eliminated peribrachial-evoked discharges in these cells, while similar applications of the muscarinic antagonist, scopolamine, were devoid of any effect. The conclusion is reached that the depolarization of lateral geniculate relay neurons by peribrachial afferents represents a direct postsynaptic effect and does not result from a global disinhibitory mechanism involving inhibition of perigeniculate cells and intrageniculate interneurons. This peribrachial-evoked transient excitation of relay neurons results from a nicotinic mechanism.

Action Potentials↗