Presynaptic Volley Research Articles

Philanthotoxins block glutamatergic transmission in rat hippocampus—II. Inhibition of synaptic transmission in the CA1 region

1. Philanthotoxins decrease the amplitude of the population spike (PS), the field excitatory postsynaptic potential (f-EPSP), and the presynaptic volley (PV), as evoked by Shaffer-collateral-commisural inputs to the CA1 pyramidal cells in the rat hippocampus slice. 2. The effects are slow and often not completely reversible. 3. Dideaza-philanthotoxin-12 is, in all experiments, the most active antagonist showing a very poor recovery. 4. Using a twin pulse the percentual decreases of f-EPSP and PV amplitudes are almost identical for the first and second response. However, the first PS is much more affected than the second one, indicating a possible effect on the inhibiting circuit. 5. Philanthotoxins cause a non-competitive inhibition. 6. Besides a possible postsynaptic block and a distinct presynaptic effect (preceding paper) a non-postsynaptic effect (on the PV) is described.

Long-term potentiation of inhibitory circuits and synapses in the central nervous system.

Glycinergic inhibition evoked disynaptically in the teleost Mauthner cell by stimulation of the contralateral eighth nerve exhibits long-term potentiation following classical tetanization of that pathway. This enhancement occurs at the synapses between primary afferents onto second-order interneurons and the connections between these inhibitory cells and the Mauthner neuron. The evidence for modifications of glycinergic transmission is that the slope of the relation between the presynaptic volley and the synaptic conductance can be greater after the tetanus. This increase in gain is still manifest after pharmacological block of potentiation at the excitatory synapse with glutamate antagonists. Inhibitory long-term potentiation is induced by tetani weaker than those required for enhancement of the monosynaptic excitation of the other (ipsilateral) Mauthner cell. Thus, in vivo learning can alter the balance between excitation and inhibition within a network by modifying one or both of them.

Serotonergic facilitation of quantal release at central inhibitory synapses

The teleost Mauthner (M)-cell is subjected to a powerful glycinergic inhibition that regulates its threshold for initiation of a vital escape reflex. The effects of 5-HT on this inhibition were studied in current- and voltage-clamp experiments because the M-cell and its afferents have a profuse serotonergic innervation, including axoaxonal contacts with terminals of the inhibitory interneurons. Local applications of the amine and/or of its uptake blockers markedly enhanced inhibitory currents evoked by synchronous activation of two identified presynaptic networks. In order to determine the site of this 5-HT action, we exploited the fact that in the M-cell, synaptic noise is predominantly inhibitory. Furthermore, its quantal components can be resolved providing a means to distinguish pre- and post-synaptic loci underlying variations in synaptic efficacy. As in other cell types, it consists of spontaneous exocytotic events and multiquantal responses triggered by action potentials in afferent neurons. 5-HT or its uptake blockers produced a long-lasting enhancement of this noise, manifested as a shift to the right of amplitude distribution histograms of the individual inhibitory postsynaptic currents (IPSCs) and an increase in the mean quantal content of noise. In contrast, the size of the miniature IPSC (mIPSCs) remained constant in these experiments and in another series where 5-HT was given in presence of TTX. In this case, the amine also increased the rate of occurrence of single quanta. Taken together, these data indicate that 5-HT acts presynaptically to increase the probability of evoked and spontaneous release of glycine. This conclusion was reinforced by evidence that the overall frequency of the responses in noise could be unaltered by 5-HT, indicating that the afferent firing pattern had remained constant. Extracellular recordings of the presynaptic volleys showed that action potentials were not prolonged and suggested that 5-HT closes K+ channels in the terminal membrane, leading to an increase of resistance and a larger depolarization in that region as a possible mechanism for the facilitation of release. While the enhancement of transmitter release persisted for 20 min or more, there was also a transient induction of a K+ inward-rectifying current in the M-cell. These results indicate that 5-HT increases the efficacy of inhibitory synaptic transmission in the vertebrate CNS by a presynaptic action.

Differential effects of (?)-baclofen on Ia and descending monosynaptic EPSPs

1. In cats anesthetized with alpha-chloralose, population synaptic responses of motoneurons produced by stimulation of group I afferents were recorded from ventral roots with a sucrose gap or extracellularly from the motor pool. These responses were depressed, and often abolished, following the intravenous injection of 1-3 mg/kg of (-)-baclofen, a presumed GABAb agonist. 2. The monosynaptic population responses of motoneurons produced by stimulation of the ipsilateral ventromedial funiculus (VMF), the bulbar reticular formation or the vestibular nucleus, were also depressed following the administration of (-)-baclofen, but to a lesser degree than responses produced by stimulation of group I fibers. 3. Depression of the synaptic actions of Ia and of descending fibers following the administration of (-)-baclofen occurred without significant changes in the presynaptic volley recorded from the cord dorsum. However, in 3/4 experiments the intraspinally recorded Ia terminal potential was reduced following the injection of (-)-baclofen. The VMF terminal potentials were also depressed, but to a lesser degree. 4. Intracellular recordings from spinal motoneurons indicate that the (-)-baclofen-induced depression of the monosynaptic Ia- and VMF-EPSPs occurred without important changes in the time course of EPSP decay. This suggests that with the amounts used, postsynaptic changes were not contributing significantly to the EPSP depression. 5. It is suggested that (-)-baclofen depresses synaptic transmission probably by activation of GABAb receptors located at the intraspinal terminations of Ia and descending fibers. The lower sensitivity of VMF actions to (-)-baclofen would be accounted for by a relatively low density of baclofen receptors in descending fiber terminals.

Effect of low glucose concentration on synaptic transmission in the rat hippocampal slice

Severe hypoglycemia in vivo is known to slow down the EEG, then to produce complete electrical silence in the brain. To find out why low glucose concentrations reduce electrical activity, synaptic transmission from Schaffer collateral/commissural fibers to CA1 pyramidal cells in the submerged rat hippocampal slice was investigated using extracellular recording techniques. Superfusion for 30 min with 1 mM glucose reversibly reduced population spike amplitude, without affecting the size of the presynaptic volley and the slope of the field EPSP. Lower glucose concentrations also affected the EPSP, although to a lesser extent than the population spike. Antidromic population spikes were not decreased by low glucose. Depolarization with 8–10 mM K + reduced both presynaptic volley amplitude and EPSP, but enhanced the population spike, an effect clearly different from that of low glucose. The slope of the input/output curve between presynaptic volley and EPSP remained unaltered in 1 mM glucose but the slope between EPSP and population spike was reduced by about 50%. Results suggest that low glucose concentrations interrupt synaptic transmission by reducing, but not abolishing, the excitability of pyramidal cells.

Postsynaptic control of the induction of long-term changes in efficacy of transmission at neocortical synapses in slices of rat brain.

1. Long-term potentiation (LTP) is an enduring, activity-induced increase in the efficacy of synaptic transmission, which has been considered as a possible neural substrate for learning. Recent experiments have shown that LTP can be induced in hippocampal CA1 neurons when a presynaptic volley is paired repetitively with depolarization of the postsynaptic cell, brought about with intracellularly applied depolarizing current pulses (20, 33). We have repeated these experiments in neocortical neurons, in transverse slices of rat sensorimotor cortex in vitro. 2. Stable intracellular recordings were obtained from 28 neurons (mean resting potential -78 mV, mean spike amplitude 95 mV, mean input resistance 41 M omega) mostly in layers V and VI. Two different afferent pathways were stimulated alternately at 0.2 Hz to evoke subthreshold composite excitatory postsynaptic potentials (EPSPs). One micromolar bicuculline methiodide was added to the bathing medium in most experiments. 3. Repetitive pairing of one afferent volley with a coincident intracellular depolarizing current pulse (100-200 ms long) of a magnitude sufficient to make the neuron fire 6 to 13 action potentials/pulse, gave rise after 30-50 pairings in 4 neurons to a significant enduring increase in the amplitude of the paired EPSP. The increase persisted without decrement for as long as the recording continued (range 15-50 min after the pairing ended) but the amplitude of the unpaired EPSP was unchanged. During the LTP, the membrane potential and the apparent input resistance of the postsynaptic neurons were also unchanged. 4. In two cells a significant prolonged depression of the paired EPSP was induced while the unpaired EPSP was unaffected. Membrane potential and input resistance were not changed. In the remaining 22 cells neither the paired nor the unpaired EPSP was altered. 5. Brief, tetanic stimulation was applied to one afferent pathway in 11 of the neurons in which postsynaptic stimulation had been ineffective. A variety of effects was produced (LTP, depression, or posttetanic potentiation). All the effects of tetanic stimulation were confined to the stimulated pathway. 6. We conclude that LTP can be produced in some neocortical neurons by pairing a presynaptic volley with postsynaptic depolarization, in an experimental paradigm that conforms to Hebb's (17) model of associative conditioning. Depression of the paired EPSP was produced in other cells with the same experimental design.(ABSTRACT TRUNCATED AT 400 WORDS)

Synaptic processes produced in cat rubrospinal neurons by stimulating the cerebellar nucleus interprositus

The activity produced in red nucleus rubrospinal neurons by stimulating the cerebellar nucleus interpositus was investigated in cats anesthetized with nembutal. Analysis of field potentials together with summated and single EPSP following paired and frequency stimulation of this structure revealed facilitation at cerebello-rubral synapses. It was found that this facilitation was not mediated by changes in presynaptic volleys. It is suggested that modification of the effectiveness of transmission is determined by characteristic features of the operation of cerebellar synapses on red nucleus neurons.

Activity-evoked increases in extracellular potassium modulate presynaptic excitability in the CA1 region of the hippocampus.

1. The effects of stimulus-evoked potassium release on the excitability of presynaptic axons were studied in the rat hippocampal slice preparation. Extracellular stimulation and recording in the stratum radiatum of CA1 yielded a characteristic field potential corresponding to the compound action potential of nonmyelinated afferents and subsequent postsynaptic activation of pyramidal cells. 2. Repetitive stimulation (1 s; 2-100 Hz) produced biphasic changes in the excitability of the afferents. Initial responses showed increased conduction velocity and variably increased amplitude; subsequent responses showed progressively decreasing conduction velocity and amplitude tending toward conduction block. Decreases in excitability were maximal at the end of stimulation and were more pronounced with higher stimulation frequencies. 3. When synaptic transmission was abolished with superfusate containing elevated [Mg2+] (6 mM) and decreased [Ca2+] (0.25 mM), kynurenic acid (1 mM), or adenosine (100 microM), the ability of the fibers to follow repetitive stimulation was enhanced, as indicated by a reduction in amplitude decrement of the presynaptic volley. The decrease in conduction velocity at the end of stimulation was less than half that obtained with intact postsynaptic activity. 4. Concomitant with changes in the excitability of CA1 afferents, the concentration of extracellular potassium ( [K+]o) increased up to 7 mM, as recorded in the stratum radiatum with potassium ion-sensitive microelectrodes. When postsynaptic activity was blocked, activity-evoked rises in [K+]o were reduced to less than 25% of their former value. This suggests that activity-evoked increases in [K+]o derive predominantly from postsynaptic elements. 5. Superfusion of solutions containing elevated [K+] produced biphasic changes in the excitability of CA1 afferents that were qualitatively similar to those produced by repetitive stimulation. Elevated [K+]o below 6 mM produced increased excitability, whereas [K+]o above 6 mM yielded decreased excitability. 6. These results demonstrate that in the CA1 region of the hippocampus, significant rises in [K+]o occur with activity and derive predominantly from postsynaptic elements. The conduction properties of CA1 afferents are sensitive to the level of [K+]o, whether altered artificially or by activity. These effects may constitute a mechanism of postsynaptic modulation of presynaptic conduction operating within a broad range of afferent firing frequencies in the hippocampus.

Quantal analysis of paired-pulse facilitation in guinea pig hippocampal slices

Intracellular excitatory postsynaptic potentials (EPSPs) were recorded in area CA 1 of hippocampal slices from guinea pigs. With paired-pulse stimulation of stratum radiatum, the second stimulus (interval of 40 50 ms) produced an EPSP with enlarged amplitude. Two methods of quantal analysis showed an increase in quantal content of the facilitated EPSP and a smaller increase in quantal size. The correlation between amplitudes of the first and second EPSP was usually insignificant. The results favour a presynaptic location of the mechanisms of the paired-pulse facilitation and suggest increases in the average of transmitter quanta released by presynaptic volley as well as increases in the amount of transmitter in each quantum.

Functional properties of the cerebellorubral synapses in the cat

Facilitation of cerebellorubral transmission was illustrated in nembutalized cats on paired stimulation of the cerebellar nucleus interpositus by an example of monosynaptic EPSPs of the rubrospinal neurons. It was found that the facilitation stated is not determined by the change in the presynaptic volley of impulses. There is reason to believe that the facilitation is determined by specific features of functioning of the cerebellar synapses on the red nucleus neurons.

Pharmacological aspects of excitatory synaptic transmission to second-order vestibular neurons in the frog.

Synaptic excitation of second-order vestibular neurons is mediated by two principal afferents: vestibular afferents projecting into the brain via the VIIIth cranial nerve and commissural afferents from the contralateral vestibular nuclear complex. The shape of the excitatory postsynaptic potentials (EPSPs) generated by selectively activating these two inputs differs qualitatively, such that ipsilateral VIIIth nerve afferents generate a faster-rising EPSP than do the commissural afferents. We have investigated the synaptic pharmacology of these two inputs in the isolated, intact medulla of the frog in order to determine the nature of the transmitter substances released by the afferents and the nature of the subsynaptic receptors with which these transmitters interact. Electrical stimulation of the ipsilateral VIIIth cranial nerve evokes in the region of the vestibular nuclear complex a field potential that exhibits a presynaptic (afferent volley) and a postsynaptic (slow negativity) component. Bath application of glutamate receptor antagonists, such as kynurenic acid (KENYA), blocks the postsynaptic component of this field potential in a dose-dependent manner, without affecting the presynaptic volley, suggesting that the VIIIth nerve afferent releases glutamate and/or similar substances as its neurotransmitter. A comparison of the actions of various glutamate receptor antagonists to block this postsynaptic negativity gives a rank order of effectiveness such that KENYA greater than gamma-D-glutamylglycine (gamma DGG) = gamma-D-glutamylaminomethylsulfonic acid (GAMS) greater than gamma-D-glutamyltaurine (gamma DGT) much greater than gamma-D-glutamylaminomethylphosphonic acid (GAMP) greater than D-2-amino-5-phosphonovaleric acid (D-APV) greater than D,L-APV greater than D-2-amino-7-phosphonoheptanoic acid (APH). This rank order of effectiveness suggests that the VIIIth nerve transmitter activates second-order neurons through kainate (KA)/quisqualate (QUIS) synaptic receptors. Intracellular studies support these conclusions. Chemically mediated EPSPs evoked from ipsilateral VIIIth nerve stimulation are completely blocked by high concentrations of KENYA (greater than or equal to 1 mM). Occasionally an extremely short-latency, probably electrically mediated, component to these EPSPs persists in the presence of KENYA. The slower-rising EPSPs evoked from contralateral VIIIth nerve or contralateral vestibular nuclear complex stimulation are also completely blocked by KENYA, suggesting that the transmitter released by the commissural afferents is also glutamate and/or related compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

An analysis of the effects of excitatory amino acid receptor antagonists on evoked field potentials in the olfactory bulb

The effects of excitatory amino acid antagonists on extracellular field potentials in the olfactory bulb produced by lateral olfactory tract stimulation were analysed in vivo. The compounds tested d-2-amino-5-phosphonovalerate, l-(+)2-amino-4-phosphonobutyrate, γ- d-glutamylglycine, l-glutamic acid diethylester and cis-2,3-piperidine dicarboxylic acid, were administered by brain dialysis. Of the compounds tested, only cis-2,3 piperidine-dicarboxylic acid and γ- d-glutamylglycine were able to suppress the synaptic excitation of granule cells. This pharmacological profile suggests the involvement of non-N-methyl- d-aspartate receptors. However, the suppression was accompanied by a reduction in the amplitude of the presynaptic volley. A second finding was that d-2-amino-5-phosphono-valerate and γ- d-glutamylglysine attenuated granule cell mediated inhibition of mitral cells, suggesting the involvement of N-methyl- d-aspartate-sensitive receptors. The possibility that mitral cells and that either centrifugal fibres, or an intrinsic olfactory bulb feedback loop might use an excitatory amino acid as its neurotransmitter is therefore discussed.

The effects of moderate changes of extracellular K + and Ca 2+ on synaptic and neural function in the CA1 region of the hippocampal slice

The effects of moderate changes of the concentration of ions on the function of mammalian central nervous tissue have not exactly been determined. We placed tissue slices from rat hippocampal formation in an interface chamber for study in vitro. Extracellular potentials were recorded in stratum radiatum and stratum pyramidale in response to stimuli of varying intensity applied to the Schaffer collateral bundle. The overall input-output relationship of excitatory synaptic transmission was gauged by expressing postsynaptic population spike amplitude as a function of presynaptic volley amplitude. The components of the transmission process were also examined by plotting (1) the maximal rate of rise (slope) of the focally recorded synaptic potential (fEPSP) as a function of presynaptic volley amplitude, and (2) the population spike amplitude as a function of the fEPSP slope. Raising the concentration of K + from the normal level of 3.5 mM to 5 mM caused an average increase of 48% in the population spike evoked by a given presynaptic volley. This was due to an increased electrical excitability of pyramidal cells, as indicated by an increase of the population spike evoked by a given magnitude of fEPSP. Conversely, lowering [K +] o from 3.5 to 2 mM caused a decrease of the population spike relative to a given magnitude of either the presynaptic volley or the fEPSP. Changing [K +] o within these limits caused no significant change of the fEPSP evoked by a given presynaptic volley. Raising [Ca 2+] o from 1.2 to 1.8 mM caused a 35% increase in both the fEPSP and the population spike evoked by a given presynaptic volley, and lowering [Ca 2+] o to 0.8 mM caused a decrease of both these functions. The amplitude of the population spikes evoked by given fEPSPs changed surprisingly little (but consistently) when [Ca 2+] o was varied within these limits. We conclude that moderate changes of [K +] o influence mainly the electric excitability of hippocampal pyramidal cells, with little effect on transmitter release or on the response of the postsynaptic membrane to transmitter, while moderate changes of [Ca 2+] o affect the release of excitatory synaptic transmitter more than they affect postsynaptic membrane function.

The effect of isoflurane on unmyelinated and myelinated fibres in the rat brain.

The effect of isoflurane on unmyelinated and myelinated fibres of the rat brain was investigated in vitro. The amplitude of the unmyelinated fibre potential (the prevolley of the hippocampal CA1 region) was reduced in a dose-dependent manner with increasing isoflurane concentrations (up to 5%). The conduction velocity was slightly decreased. The minimal alveolar concentration (MAC) anesthetizing 50% of the animals is 1.38%. At this concentration the presynaptic volley was reduced by 18% and the conduction velocity was decreased by about 1%. The effect on myelinated fibres (fimbria) was small and significantly different from the effect on unmyelinated fibres (P = 0.03 and 0.005 at 1 and 2% isoflurane, respectively.

Influence of electric fields on the excitability of granule cells in guinea-pig hippocampal slices.

1. Monosynaptic evoked potentials were recorded from the granule cell layer of slices of guinea-pig hippocampus maintained in vitro. Current pulses of 25-250 msec duration were passed across the slices, between gross electrodes in the bathing liquid. 2. Polarizing current modified the excitability of the granule cells as judged by changes in their population discharge during postsynaptic responses. All durations of polarization had at least qualitatively similar effects. Conventional current from dendrites to cell bodies increased excitability (and vice versa). This is consistent with altered membrane potential of a spike trigger zone, at or close to the granule cell bodies, imposed by the fraction of polarizing current which flows intracellularly. 3. In some experiments polarization also affected the presynaptic volley and (hence?) the synaptic potential. When this occurred it was in the wrong sense to explain the concomitant changes in population spike. 4. Focal polarization, where currents were applied across the cell body layer between a small electrode on the mid or outer dendritic regions and a remote gross electrode, altered granule cell excitability in the same direction as in (2). Thus conventional current injected at the dendritic electrode increased excitability. 5. The smallest effect polarizing currents caused extracellular voltage gradients of 5-10 mV/mm, which is less than occurs in this tissue during synchronous activation of the neurons or during seizure activity. Therefore such field potentials could increased the synchrony of discharge of the granule cells.

Prevertebral (oesophageal) recording of subcortical somatosensory evoked potentials in man: The spinal P 13 component and the dual nature of the spinal generators

Short-latency somatosensory evoked potential (SEP) components to median nerve or finger stimulation were recorded in 12 normal young adults with 14 channels, using a non-cephalic reference. Several electrodes were placed along the posterior neck, earlobes and scalp while oesophageal probes provided 2–6 recording sites at known levels in front of vertebrae C2 to Th3 (Fig. 1). The oesophageal electrodes provided a new non-invasive point of entry that secured important data about the generator sources of the spinal SEP components. All cephalic electrodes recorded a P 9 far field which is greater over the scalp, earlobes and rostral cervical spine than over the caudal cervical spine. P 9 is the volume-conducted peripheral nerve volley coursing between axilla and spinal cord. The direct recording of arrival times of the peripheral volley along the median nerve and brachial plexus (Erb's point) served to estimate the spinal entry time which coincided with the onset of the posterior neck N 11 (at levels C6-C7) and of the scalp P 11 far field (Fig.3). The latency shift of the onset of N 11 from lower to upper neck has been replicated (Fig. 8C, D) and N 11 is interpreted as a presynaptic volley ascending the dorsal column (central branch of the primary neurone) at a velocity of 58 m/sec (Desmedt and Cheron 1980a). At oesophageal electrodes in front of the C7-Th3 vertebrae, the first negative component starts before the spinal entry time and it corresponds to action potentials in the spinal roots (Figs. 2 and 3). The most remarkable feature of oesophageal recordings in front of the C3 to Th2 vertebrae is the positive P 13 component which represented a phase reversal of the second negativity N 13 recorded from posterior neck (Fig. 5). The P 13-N 13 phenomenon was recorded in all subjects and presented a stable latency throughout the cervical cord (Fig. 6C). It was clearly differentiated from the scalp far-field P 14 which is related to the ascending volley in the median lemniscus (Figs. 5 and 8; Tables I and II). The spinal P 13 did not extend above C2 and it was obviously generated below the foramen magnum. P 13 is interpreted as a dorsal horn postsynaptic potential which is elicited by collateral branches of the (bifurcated) primary afferent fibre. The use of 14 simultaneous recordings including a series of pre- and post-vertebral electrodes clearly identified two distinct generators for the spinal SEP components to median nerve stimulation: a presynaptic generator which ascends the dorsal column (N 11) and a postsynaptic fixed generator in the dorsal horn of the cervical spinal cord (N 13-P 13).

Possible mechanisms for long-lasting potentiation of synaptic transmission in hippocampal slices from guinea-pigs.

1. Long-lasting potentiation of synaptic transmission was studied in the CA1 region of guinea-pig hippocampal slices maintained in vitro. 2. Stimulating pulses were delivered alternately to two independent afferent pathways, stratum radiatum and stratum oriens. The presynaptic volleys and field e.p.s.p.s. were recorded from the same two layers, while an electrode in the pyramidal cell body layer recorded the population spike or in other experiments the extra- or intracellular potentials from a single pyramidal cell. 3. A short tetanus to either of the two input pathways produced a long-lasting enhancement of the field e.p.s.p. as well as an increased size and a reduced latency of the population spike. This long-lasting potentiation was observed for up to 110 min after tetanization. Extracellular unit recordings showed that this potentiation is accompanied by an increased probability of firing and a reduced firing latency. Intracellular recordings showed an increased e.p.s.p., through the increase was smaller and less regular than for the extracellular field e.p.s.p. 4. No corresponding changes were seen in the field potential responses to stimulation of the untetanized input path, or in the intracellularly measured soma membrane potential, resistance, or excitability. The latter two properties were measured by intracellular injection of current pulses. It is concluded that long-lasting potentiation is specific to the pathway which has received the tetanization. 5. Following tetanization there was also a short-lasting (usually 2-4 min) depression, most often seen for the control pathway but sometimes visible on the tetanized side as well, superimposed on the potentiation. It is concluded that the short-lasting depression is not confined to any particular pathway but is a generalized (unspecific) phenomenon.

Intracellular responses from granule cell layer in slices of rat hippocampus: perforant path synapse.

Intracellular responses were recorded in vitro from the denate granule cell layer of hippocampal slices prepared from adult rats. Spontaneous activity of granule cells in vitro consisted of action potentials and small, graded depolarizations, presumably of synaptic origin. Granule cells could be activated by injection of depolarizing current or release of hyperpolarizing current. Individual granule cells spatially summed input from the perforant path and fired multiple action potentials in vitro following strong presynaptic volleys. Depolarization decreased and hyperpolarization increased the EPSP amplitude, which is consistent with a conductance-increase mechanism. Although we could demonstrate postexcitatory inhibition in some cells, granule cells in vitro appeared to receive less inhibitory feedback than in vivo, EPSP amplitude and spike output of granule cells showed frequency potentiation and posttetanic potentiation to perforant path stimulation. These intracellular responses in vitro complement some of the findings from field-potential analyses of the dentate gyrus in intact animals.

Ultrastructure of cortical synapses after failure of presynaptic activity in ischemia.

AbstractThe fine structure of cerebral cortical synapses was investigated during failure of synaptic transmission produced by ischemia. Presynaptic and postsynaptic potentials evoked in the anterior sigmoid gyrus of the cat by stimulation of the nucleus ventralis lateralis and the DC potential between cortical layer IV and the white matter were recorded with micropipettes during cerebral ischemia produced by arterial hemorrhage in paralyzed, artificially ventilated animals. After failure of the spontaneous electrocorticogram and postsynaptic responses, the presynaptic volley failed with development of depolarization of intracortical fiber terminals and loss of axon terminal excitability. The gyrus was then biopsied and fixed in collidine‐buffered OsO4. An altered pattern of distribution of synaptic vesicles was observed after presynaptic afferent fiber terminal activity was abolished by 3.5 to 4.0 minutes of cerebral ischemia. Clumping of vesicles in a region away from the cynaptic cleft was seen in about 10% of synaptic endings, and there was more than a two‐fold increase in the number of presynaptic profiles devoid of vesicles in ischemic cortex.

The synaptic link between the sensory and motoneurones in the eye-withdrawal reflex of the crab.

ABSTRACT The axon of the larger of the two motoneurones in the optic tract of Carcinus which bring about the rapid eye withdrawal is 30–50 µ in diameter and has an unusually thin sheath compared with crab leg neurones of similar diameter. Within the brain the axon of the large eye-withdrawal motoneurone tapers fairly rapidly to 5–10µ. It extends diagonally across one side of the brain and branches in two near the mid line but does not pass the contralateral side of the brain. The axon terminals and the cell body have not been seen. A single stimulus to the afferent inputs of the motoneurone produces a characteristic burst of impulses followed by an irregular train of impulses. The excitatory effects of all tested afferent inputs to the motoneurone are summed before affecting a common spike-initiating locus on the motoneurone. Intracellular recordings from the motoneurone within the brain show two types of subthreshold activity to follow a single pre-synaptic volley : a smooth graded depolarization and small superimposed depolarizations of constant amplitude and duration. The synaptic link between afferents and the eye-withdrawal motor neurone is thought to be via a direct, possibly monosynaptic pathway and also by way of interneurone collaterals.