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PubMed1969

Transmission from pregnanglionic fibres in the hypogastric nerve to peripheral ganglia of male guinea-pigs.

1. Intracellular records were obtained from ganglion cells of the pelvic plexus of male guinea-pigs.2. The input resistance of cells which responded to intracellular stimulation varied from 40 to 150 MOmega. Slope resistance decreased when the membrane was hyperpolarized. Time constants varied from 5 to 200 msec. Resting membrane potentials ranged from 40 to 70 mV.3. Action potentials in response to direct stimulation were followed by a prolonged phase of after-hyperpolarization.4. A second type of cell was also impaled which did not respond to electrical stimulation. These cells had resting membrane potentials in the range 60-70 mV, input resistances of less than 20 MOmega and time constants of less than 3 msec.5. In most ganglion cells, stimulation of the hypogastric nerve evoked action potentials which were often followed by a secondary phase of depolarization indicating continuing transmitter action.6. Orthodromic responses were generally ;all-or-nothing' and could not be graded with changes in stimulus strength. The latency of orthodromic responses indicated that ganglion cells were innervated by both B and C fibres in the hypogastric nerve.7. Orthodromic responses were blocked by tubocurarine, 5 x 10(-5) g/ml., and dihydro-beta-erythroidine, 10(-5) g/ml.8. Spontaneous, excitatory post-synaptic potentials of up to 4.8 mV in amplitude were observed. The frequency of their discharge was greatly increased by repetitive stimulation of the hypogastric nerve.9. The ultrastructure of the pelvic ganglia was studied by electronmicroscopy. Two types of ganglion cell process were observed, fine (0.1 mu) branching tufts thrown up from the soma within the surrounding capsule and longer, thicker (1 mu) extracapsular processes. Synapses were found to occur most frequently between the varicose terminal segments of preganglionic axons and the small intracapsular processes.10. Similarities between the properties of the pelvic ganglia innervated by the hypogastric nerve and those of the parasympathetic division of the autonomic nervous system are discussed.

Action Potentials↗
PubMed1978

Synaptic connections to individual tibialis anterior motoneurones in man.

The characteristics of post-synaptic potentials in a single human motoneurone can be derived from the profiles of post-stimulus time histograms (PSTH) of that neurone when it is firing rhythmically. We have used this method to explore the synaptic connections to individual tibialis anterior motoneurones in man. Agonist group 1 volleys produced short latency excitation of 85% of tibialis anterior motoneurones probably representing the 1a EPSP. Excitation, at a latency of 70 ms, is attributed to a long loop reflex. Antagonist group 1 volleys produced short latency inhibition of 65% of tibialis anterior motoneurones probably representing the 1a IPSP. Excitation, at a latency of 97 ms, may represent spino-bulbo-spinal reflex. None of these effects are due to the excitation of cutaneous afferent nerve fibres.

Action Potentials↗
PubMed1980

Segmental innervation of rotated and supernumerary axolotl hindlimbs.

The segmental nerve supply to axolotl limbs was misrouted by severing the limbs at the level of the femur, rotating them 180 degrees around their long axis, and then suturing them to the intact proximal stump. Following return of the blood supply to the rotated limb by the cross-anastomosing of blood vessels, a blastema often formed to the side of the rotation site giving rise to a supernumerary limb. The muscles of both rotated and supernumerary limbs were innervated by the segmental nerves. The percentage of cells innervated by segmental nerves 16 and 17 in each muscle was determined with intracellular electrodes at 14 weeks after the operation. Despite histological evidence that nerves had been misrouted in the rotated limb, the percentage innervation of each muscle by nerves 16 and 17 was similar to that in the unoperated contralateral controls. The same results were obtained for the supernumerary limbs. In some muscles a few synaptic sites were found innervated by segmental nerves which did not innervate that muscle in the contralateral controls. These had synaptic potentials with very low quantal contents if immediately adjacent sites were innervated by the segmental nerve, which did innervate that muscle in the contralateral controls. The results suggest that the selective properties of synaptic sites are alone sufficient to determine the entire segmental innervation pattern of the muscles in a limb.

Ambystoma↗
PubMed1992

Extracellular recordings from the motor nervous system of the nematode, Ascaris suum.

1. The close association of muscle and neurons in Ascaris suum makes it difficult to determine whether spikes recorded from nerve cords originate in muscle or neurons. We have developed criteria that distinguish muscle and neuronal activity. There are two categories of extracellular spikes. 2. The first category consists of spikes with a wide range of amplitudes, marked by large spikes. These spikes, which can be recorded over lateral muscle and over the dorsal and ventral nerve cords, are abolished when muscle is disrupted or removed, or when curare is applied. Large spikes are relatively infrequent, are correlated with intracellularly recorded muscle events, and respond to polarizations of motor neurons, implying that they originate in muscle. 3. The second spike category, small amplitude spikes, is exclusive to the ventral nerve cord, occurs more frequently than large spikes and displays patterned firing. Small spikes are not affected by muscle removal or by curare, and are correlated with motor neuronal post-synaptic potentials, but not with intracellularly recorded muscle events. We infer that they originate in neurons. 4. Low level activity recorded extracellularly over nerve cords may represent muscle activity due to tonic motor neuronal synaptic transmission. It responds to motor neuronal polarization and is suppressed by curare or muscle removal.

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↗
PubMed2005

Minis: whence and wherefore?

In this issue of Neuron, Sara et al. find that spontaneously released miniature synaptic potentials arise from a pool of vesicles distinct from those released by neural activity. This modification of a basic tenet of the quantal hypothesis has important implications for the analysis of changes in synaptic transmission.

Animals↗
PubMedDate not supplied

Cyclic-nucleotide-gated channels mediate synaptic feedback by nitric oxide.

Cyclic-nucleotide-gated (CNG) channels in outer segments of vertebrate photoreceptors generate electrical signals in response to changes in cyclic GMP concentration during phototransduction. CNG channels also allow the influx of Ca2+, which is essential for photoreceptor adaptation. In cone photoreceptors, cGMP triggers an increase in membrane capacitance indicative of exocytosis, suggesting that CNG channels are also involved in synaptic function. Here we examine whether CNG channels reside in cone terminals and whether they regulate neurotransmitter release, specifically in response to nitric oxide (NO), a retrograde transmitter that increases cGMP synthesis and potentiates synaptic transmission in the brain. Using intact retina, we show that endogenous NO modulates synapses between cones and horizontal cells. In experiments on isolated cones, we show directly that CNG channels occur in clusters and are indirectly activated by S-nitrosocysteine (SNC), an NO donor. Furthermore, both SNC and pCPT-cGMP, a membrane-permeant analogue of cGMP, trigger the release of transmitter from the cone terminals. The NO-induced transmitter release is suppressed by guanylate cyclase inhibitors and prevented by direct activation of CNG channels, indicating that their activation is required for NO to elicit release. These results expand our view of CNG channel function to include the regulation of synaptic transmission and mediation of the presynaptic effects of NO.

Ambystoma↗
PubMed1966

Anomalous rectification in the metacerebral giant cells and its consequences for synaptic transmission.

1. In the central neurones that have so far been examined the passive electrical properties of the extrasynaptic membrane has been shown to be relatively constant in the subthreshold range. Consequently, excitatory synaptic potentials produced by chemical transmission tend to vary in amplitude with changes in membrane potential, decreasing with depolarization and increasing with hyperpolarization.2. In the two symmetrical giant cells of the ventral metacerebrum of the snail, the EPSPs failed to show the expected alterations in amplitude with changes in membrane potential. Near the resting level the EPSP increased slightly with membrane depolarization and decreased slightly with hyperpolarization.3. These paradoxical results were not attributable to a change in transmitter release since similar results were obtained when ACh, the putative transmitter, was released iontophoretically on to the cell membrane by means of an extracellular pipette.4. Measurement of the current-voltage relation of the extrasynaptic membrane revealed two types of rectifying conductance changes. The first, an increase in conductance with depolarization, was turned on at a depolarization of about 15 mV. Its conductance change was similar to the delayed rectification familiar from studies of peripheral nerve and muscle. The second occurred on either side of the resting level, from about 15 mV hyperpolarization to about 10 mV depolarization, and manifested itself as a decrease in conductance with depolarization and an increase with hyperpolarization. By analogy to a similar phenomenon known to occur in skeletal muscle this second rectification has been termed anomalous rectification.5. The average resistance at 25 mV hyperpolarization was 2.3 x 10(6) Omega, while at 10 mV depolarization it was 2.1 x 10(7) Omega, yielding an average rectification ratio of 10 for the anomalous conductance change.6. The anomalous rectifying conductance seems to account for the paradoxical behaviour of the EPSP and ACh response to changes in membrane potential. Moreover, the finding that the sharpest change in the anomalous rectification curve occurred on either side of the resting level suggests that this rectification is functionally important as a postsynaptic determinant of synaptic efficacy. Several additional lines of evidence in support of this suggestion have been obtained.

Acetylcholine↗
PubMed1989

Chronic epileptic foci in vitro in hippocampal slices from rats with the tetanus toxin epileptic syndrome.

1. Minute doses of tetanus toxin were injected into the hippocampi of rats, under pentobarbitone anesthesia, to induce a chronic experimental epilepsy. The effects of this treatment were studied in vitro in hippocampal slices prepared 1-60 days after injection. 2. Epileptic activity was preserved in these slices in vitro, closely resembling that seen in vivo. Epileptiform afterdischarges were evoked by stimulation after survival times of greater than or equal to 3 days from injection. Spontaneous synchronous epileptic discharges were recorded from 7 days after injection. Both kinds of epileptiform activity were found with survival times up to 36 days but not beyond 44 days. This time course resembles the waxing and waning of the epileptic syndrome in vivo. 3. Two distinct types of spontaneous burst were seen. The first was a simple burst lasting 100-300 ms, reminiscent of the "interictal spike" of the clinical electroencephalogram. The second was much more prolonged, lasting several seconds. It consisted of a simple burst followed by a series of discrete afterbursts at 3-6/s and resembled the early stages of an epileptic seizure. Both types of burst were associated with slow field potentials that were positive at the cell-body layer. 4. Both the interictal and the seizure-like spontaneous epileptic discharges originated in the CA3b/c pyramidal cell region and propagated at 0.1-0.25 m/s along the cell layer toward the CA1 region. They occurred at very variable intervals, ranging from 20 s to 30 min. 5. Spontaneous epileptic bursts occurred in media containing 3 mM [K+]o to 5 mM in one-third of experiments during the period 1-4 wk after injection. Spontaneous bursts could be induced by increasing [K+]o to 5 mM in two-thirds of the remaining slices, which initially had produced evoked afterdischarges. 6. Intracellular recordings revealed that spontaneous field bursts were invariably associated with paroxysmal depolarization shifts (PDSs) and bursts of action potentials, suggesting that almost all the pyramidal cells in the region were recruited into the epileptic discharges. In some cells, smaller abnormal depolarizations were also seen; they were clearly larger than the spontaneous synaptic potentials but were not associated with field potentials. They may have been due to a more limited recruitment of pyramidal cells into partially synchronous bursts. 7. The tetanus toxin experimental epileptic syndrome differs from chronic models described previously in retaining in the hippocampal slice in vitro much of the spontaneous epileptic activity seen in vivo in the freely moving chronically epileptic rat.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Central circuitry in the jellyfish Aglantha. II: The ring giant and carrier systems

1. The ring giant axon in the outer nerve ring of the jellyfish Aglantha digitale is a multinucleate syncytium 85 % of which is occupied by an electron-dense fluid-filled vacuole apparently in a Gibbs­Donnan equilibrium with the surrounding band of cytoplasmic cortex. Micropipette recordings show small (-15 to -25 mV) and large (-62 to -66 mV) resting potentials. Low values, obtained with a high proportion of the micropipette penetrations, are assumed to be from the central vacuole; high values from the cytoplasmic cortex. Background electrical activity includes rhythmic oscillations and synaptic potentials representing hair cell input caused by vibration. 2. After the ring giant axon has been cut, propagating action potentials evoked by stimulation are conducted past the cut and re-enter the axon on the far side. The system responsible (the carrier system) through-conducts at a velocity approximately 25 % of that of the ring giant axon and is probably composed of small neurones running in parallel with it. Numerous small neurones are seen by electron microscopy, some making one-way and some two-way synapses with the ring giant. 3. Despite their different conduction velocities, the two systems normally appear to fire in synchrony and at the velocity of the ring giant axon. We suggest that, once initiated, ring giant spikes propagate rapidly around the margin, firing the carrier neurones through serial synapses and giving them, in effect, the same high conduction velocity. Initiation of ring giant spikes can, however, require input from the carrier system. The spikes are frequently seen to be mounted on slow positive potentials representing summed carrier postsynaptic potentials. 4. The carrier system fires one-for-one with the giant axons of the tentacles and may mediate impulse traffic between the latter and the ring giant axon. We suggest that the carrier system may also provide the pathways from the ring giant to the motor giant axons used in escape swimming. 5. The findings show that the ring giant axon functions in close collaboration with the carrier system, increasing the latter's effective conduction velocity, and that interactions with other neuronal sub-systems are probably mediated exclusively by the carrier system.

Journal Article↗
PubMed1994

Synaptic facilitation at connections of Hermissenda type B photoreceptors.

The enhancement of excitability in type B photoreceptors is an important neural mechanism underlying classically conditioned suppression of phototaxis in the marine mollusk Hermissenda crassicornis. However, the possibility that type B photoreceptors also exhibit synaptic plasticity has not previously been explored. We now report that connections of type B photoreceptors onto type A photoreceptors exhibit synaptic facilitation, and that this facilitation involves the same first messenger (5-HT) and second messenger (protein kinase C) previously implicated in the learning-produced excitability changes. In brief, we found that application of 5-HT dramatically facilitates synaptic potentials evoked by type B cells in type A cell cells, and that this facilitation is blocked by preincubation with staurosporine, a protein kinase inhibitor. Furthermore, activation of protein kinase C also induces synaptic facilitation, whereas activation of the cAMP-dependent protein kinase has no effect. Changes in synaptic strength produced by these manipulations are paralleled by changes in type B cell input resistance (a simple index of cellular excitability), whereas type A cell input resistance is unaffected. These findings indicate a previously unrecognized form of neuronal plasticity in Hermissenda that may contribute importantly to the learned changes in behavior, and thereby highlight general principles of learning-related neuronal plasticity shared by different preparations and species.

Alkaloids↗
PubMedDate not supplied

Effects of neuropeptide Y on evoked potentials in the CA1 region and the dentate gyrus of the rat hippocampal slice.

The effects of exogenously applied neuropeptide Y (NPY) on evoked field potentials in the CA1 area and dentate gyrus were examined in the in vitro hippocampal slice preparation from rate. The amplitudes of extra-cellularly recorded field potentials from the CA1 region were depressed by NPY (0.1-0.5 microM) in a dose-dependent manner. NPY had only little inhibitory effect in the area dentata. Similar effects were observed when synaptic excitation was recorded in the presence of the GABA(A) receptor antagonist picrotoxin. In the presence of picrotoxin, NPY reduced epileptiform discharges evoked in the disinhibited CA1 pyramidal cells suggesting that NPY may have antiepileptic action in this area. The effect of NPY on epileptiform discharges evoked in granule cells was minor. When NMDA-receptor mediated component of excitatory synaptic transmission was revealed in Mg2+ -free solution, NPY diminished both non-NMDA and NMDA receptor-mediated components of the field excitatory synaptic potentials recorded in the CA1 region. Such an effect is line with the reduction of glutamate release at the Schaffer collateral/commissural terminals by NPY.

2-Amino-5-phosphonovalerate↗
PubMed1984

Synaptic actions produced by individual ventrolateral tract fibres in frog lumbar motoneurones.

Excitatory post-synaptic potentials (EPSPs) were evoked in lumbar motoneurones of the isolated frog spinal cord by impulses in single ventrolateral tract fibres. In a few cases after recording an EPSP the fibre and the motoneurone involved were both filled with horseradish peroxidase (HRP) and the synaptic connexion between them was studied histologically. Monosynaptic EPSPs produced by direct stimulation of supraspinal (mainly reticulospinal) or unidentified (presumably propriospinal) fibres are mediated via chemical and, less frequently, dual-action synapses. The shape indices of chemical single-fibre EPSPs varied considerably in different connexions being, as a whole, similar to those of chemical components of EPSPs at synapses between primary afferents and motoneurones. Quantal analysis of the single-fibre EPSPs yielded quantal unit amplitude 18-113 microV and mean quantum content ranging from 1.14 to 16.4, the applicability of both Poisson and binomial models to transmitter release was revealed. Descending fibres electrically coupled with lumbar motoneurones were found to generate a depolarizing response to dorsal root stimulation. They were also characterized by a larger depolarization to superfused glutamate. The presence of electrical junctions between descending axons and spinal motoneurones suggests that the depolarization seen in these axons in response to synaptic excitation and glutamate could be the result of passive flow of depolarizing current from motoneurones electrically coupled to them. gamma-aminobutyric acid (GABA) did not produce conspicuous actions in axons forming both chemical and dual-action synapses. Axons injected with HRP have been followed to their site of termination in the lateral motor column. Synaptic boutons and varicosities were found to form contacts predominantly with dendrites of target motoneurones.

Animals↗
PubMed1993

Activity-mediated changes in feed-forward inhibition in the dentate commissural pathway: relationship to EPSP/spike dissociation in the converging perforant path.

1. We tested the hypothesis that long-term synaptic potentiation (LTP)-associated excitatory postsynaptic potential (EPSP)/spike dissociation in the dentate gyrus (DG) is determined, in part, by changes in the feed-forward inhibition evoked by perforant path (PP) stimulation. The dentate commissural pathway (CP) and the PP activate a common pool of interneurons. Therefore a change in synaptic efficacy in the inhibitory circuit due to activation of one pathway could lead to changes in inhibitory efficacy in the other. The relationship between changes in feed-forward inhibition in the CP and EPSP/spike (E-S) functions in the PP should provide information about the site(s) of synaptic modification. 2. In urethan-anesthetized rats, we measured the inhibition of evoked PP population spikes by the CP at interstimulus intervals of 6 and 12 ms. This measure of commissural inhibition and conventional E-S functions for the PP input to the DG were obtained before and after 1) PP tetany (400 Hz, 8-pulse trains) at low, medium, and high stimulus intensities, and 2) CP tetany (200 Hz, 7-pulse trains). 3. Low-intensity PP conditioning (just above population spike threshold) led to a decrease in CP inhibition and large left shifts of the E-S function. High- and medium-intensity PP conditioning yielded increases in commissural inhibition and smaller leftward E-S shifts. 4. Commissural conditioning led to increases in commissural inhibition and inconsistent changes in the E-S functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMedDate not supplied

[Transmission in the sensorimotor synapses of the lumbar spinal cord in Rana ridibunda tadpoles].

In experiments on preparations of isolated spinal cord of the tadpoles, intracellular studies have been made on the synaptic potentials evoked in the lumbar motoneurones during total activation of the fibers within the 9th dorsal root. It was shown that primary afferents form monosynaptic contacts with motoneurones at stages XIV-XXV. During larval development, the number of motor cells in which monosynaptic EPSPs are recorded increases, whereas the number of motoneurones with only polysynaptic reactions decreases. From the moment of formation of monosynaptic contacts, transmission in direct sensory-motor synapses is realised by a dual (electrical-chemical) mode. The data obtained are discussed in relation to the problem of evolution of synaptic transmission between heterotypic neurones in vertebrates.

Animals↗
PubMed2000

Functional role of NMDA autoreceptors in olfactory mitral cells.

The output of the olfactory bulb is governed by the interaction of synaptic potentials with the intrinsic conductances of mitral cells. While mitral cells often are considered as simple relay neurons, conveying activity in olfactory receptor cells to the piriform cortex, there is strong physiological and behavioral evidence that local synaptic interactions within the olfactory bulb modulate mitral cell discharges and facilitate odorant discrimination. Understanding the circuitry of the olfactory bulb is complicated by the fact that most dendrites in this region are both pre- and postsynaptic. Feedback inhibition is mediated through reciprocal dendrodendritic synapses between the secondary dendrites of mitral cells and GABAergic granule cells. Here we show that glutamate released from mitral cell dendrites also activates local N-methyl-D-aspartate (NMDA) autoreceptors, generating an inward tail current following depolarizing voltage steps. Autoreceptor-mediated self-excitation is calcium dependent, can be evoked by single action potentials in the presence of magnesium, and is graded with the number of spikes in a train. We find that dendrodendritic inhibition also is evoked by single action potentials but saturates rapidly during repetitive discharges. Self-excitation also underlies the prolonged afterdischarges apparent in mitral cells following potassium channel blockade. Both afterdischarges and autoreceptor-mediated tail currents persist in TTX, suggesting that they are produced by local rather than polysynaptic actions of glutamate. Blockade of NMDA autoreceptors with 2-amino-5-phosphonovaleric acid (APV) reduces the firing frequency within action potential cluster. The rapid kinetics of self-excitation suggests a functional role of NMDA autoreceptors in prolonging periods of phasic firing in mitral cells.

2-Amino-5-phosphonovalerate↗
PubMed1993

Electrophysiological identification of horizontal synaptic connections in rat visual cortex in vitro.

The presence of intrinsic horizontal synaptic connections in rat visual cortex was explored electrophysiologically using in vitro slice preparations. Intracellular recordings were made from pyramidal neurons located in the superficial and deep layers. Electrical stimulation at the gray matter in the same or different layers but 0.8-2.7 mm apart from the recording site evoked compound synaptic potentials composed of excitatory and inhibitory postsynaptic potentials of fast and slow time courses. Glutamate blockers, DNQX (5 microM) and kynurenate (2 mM) reduced the excitatory postsynaptic potential (EPSP), and GABAB receptor antagonist, phaclofen (0.5 mM), abolished the inhibitory postsynaptic potential of the slow time course. EPSP of the fast time course followed 20 Hz repetitive stimulation in the medium of high Ca2+ (6.0 mM) and Mg2+ (4.0 mM) concentration, suggesting that this fast EPSP was monosynaptic. Conduction velocity of the fibers mediating the monosynaptic EPSP was estimated to be 0.15-0.55 m/s. These results provide physiological evidence for the horizontal synaptic connections in the rat visual cortex, which had been previously suggested by morphology.

Animals↗
PubMed1966

Interaction experiments on the responses evoked in Purkinje cells by climbing fibres.

1. The uniquely powerful excitatory synaptic action of a single climbing fibre on a Purkinje cell in the cerebellum of the cat was tested during the intense and prolonged inhibitory action produced by the parallel fibre, basket and stellate cell system. There was depression of the later spike discharges, but the initial discharge was never suppressed.2. With intracellular recording the excitatory post-synaptic potential was depressed during the initial phase (about 10 msec) of the inhibitory action, but there was a later increase with a time course resembling the latter part of the inhibitory hyperpolarization. An explanation of these and other effects is given in terms of conventional ideas of excitatory and inhibitory synaptic interaction.3. These observations on single Purkinje cells, particularly with intracellular recording, have helped in formulating a provisional explanation of the finding that during inhibition there is an increase in the negative field potential evoked by a climbing fibre volley.4. The excitatory action of a climbing fibre synapse is shown to be greatly depressed immediately after a preceding activation and recovery takes hundreds of milliseconds. By the collision technique it is shown that the same climbing fibre is activated by inferior olive and juxta-fastigial stimulation.5. With rapid repetitive activation there was initially a progressive decline in the effectiveness of each successive impulse, but a steady level was soon reached. On cessation of a tetanus of twenty or more impulses there was a delayed recovery of the depolarization, which suggests a continued action of the accumulated transmitter.6. With extracellular recording repetitive spike initiation continued with stimulation frequencies as high as 100/sec, but at still higher frequencies spikes were depressed by the intense synaptically evoked depolarization. On cessation of the stimulation after-discharge often developed as the depolarization declined. The prolonged after-discharges following severe tetani suggest that there is a very effective accumulation of the transmitter.

Animals↗