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An ultrastructural size principle.

Recent ultrastructural descriptions of synaptic contacts suggest that potential synaptic efficacy may be directly correlated with bouton size. The characteristics of a synaptic bouton which presumably underlie its potential physiological strength (such as vesicle number, active zone number and area, and mitochondrial volume) are all linearly related to the volume of the bouton. Furthermore, at synapses which contact dendritic spines in both the hippocampus and cerebellum, the volume of the spine is linearly related to bouton volume. The existence of these scaling relationships has widespread implications for interpreting synaptic anatomy and variability, and for examining synaptic plasticity. We review evidence in support of the "ultrastructural size principle" outlined above and its potential generality.

Animals↗

Fate of abdominal ventral unpaired median cells during metamorphosis of the hawkmoth, Manduca sexta.

Each of the unfused abdominal ganglia in the larval, pupal, and adult stages of the hawkmoth, Manduca sexta, has two large ventral median neurons with axons that bifurcate to innervate targets on both sides of the abdomen. Although the dendritic structures of the two neurons are similar, their axons branch to innervate distinct sets of target muscles. During metamorphosis both neurons undergo dendritic regression, followed by growth of new arborizations during adult development. The neurons must innervate different targets in the larva and adult, since many larval muscles degenerate and are replaced during metamorphosis. Both neurons were reactive with an antibody to the neuromodulatory compound, octopamine, in the larval and adult stages. Pairwise intracellular recordings in isolated nerve cords revealed spontaneous excitatory synaptic potentials that occurred in the ventral median neurons of each ganglion in an anterior-to-posterior sequence. The synaptic potentials were eliminated when the interganglionic connective was interrupted posterior to the subesophageal ganglion. The ventral median neurons were also excited by tactile stimulation of the body surface in larvae, pupae and adults.

Abdomen↗

Synaptic activation of an electrogenic sodium pump.

An identified molluscan interneuron mediates different cholinergic synaptic actions by increasing the conductance of its follower cells to different ions. We have now found that this interneuron also mediates a new class of synaptic actions which does not involve a conductance change but the activation of an electrogenic sodium pump. This synaptic action results in a prolonged inhibitory synaptic potential which is dependent on metabolism and is selectively blocked by cooling and ouabain. In cells which have this synaptic potential, part of the resting membrane potential is also maintained by an electrogenic sodium pump. The same transmitter, acetylcholine, can independently stimulate both a chloride ion conductance and a sodium pump mechanism in the same follower cell by acting on two different postsynaptic receptors.

Acetylcholine↗

Sources of variation in the output of locust spiracular motoneurones receiving common synaptic driving.

1. The closer muscles of the left and the right spiracles of a thoracic segment are both innervated by two motoneurones, which spike in a variety of patterns during expiration. This paper seeks to explain the origin of these patterns. 2. No direct coupling between the two motoneurones is revealed. In an isolated thoracic ganglion both motoneurones spike at different frequencies with no tendency for their spikes to become synchronized. 3. The two closer motoneurones in one segment receive common, patterned depolarizing synaptic potentials during expiration caused by interneurones relaying information from the metathoracic ganglion. 4. The closer motoneurones of all the thoracic segments receive the same pattern of synaptic potentials from these interneurones. Despite this, the spiracles of one segment may remain shut while those on other segments continue to open and close rhythmically. 5. The interplay between common synaptic driving, the threshold of the motoneurones for spike initiation, and the tendency for a motoneurone to spike at a particular frequency even in the absence of interneuronal driving, explains the various patterns of spikes during expiration. Common synaptic driving imposes the same basic pattern of commands on all the motoneurones, but the individual motoneurones determine the final pattern of motor spikes. 6. To be effective in producing a patterned output, an input pattern must operate within narrow limits on either side of the threshold of the motoneurone. If the depolarization is too large, a high frequency of unpatterned spikes will result; if too small, then either there will be no output or a low frequency of spikes will result whose patterning will be affected by other inputs.

Action Potentials↗

Long-term potentiation of synaptic transmission at the mossy fiber-granule cell relay of cerebellum.

In the last decade, the physiology of cerebellar neurons and synapses has been extended to a considerable extent. We have found that the mossy fiber-granule cell relay can generate a complex form of long-term potentiation (mf-GrC LTP) following high-frequency mf discharge. Induction. Mf-GrC LTP depends on NMDA and mGlu receptor activation, intracellular Ca(2+) increase, PKC activation, and NO production. The preventative action of intracellular agents (BAPTA, PKC-inhibitors) and of membrane hyperpolarization, and the correlated increase in intracellular Ca(2+) observed using fluorescent dyes, indicate that induction occurs postsynaptically. Expression. Expression includes three components: (a) an increase of synaptic currents, (b) an increase of intrinsic excitability in GrC, and (c) an increase of intrinsic excitability in mf terminals. Based on quantal analysis, the EPSC increase is mostly explained by enhanced neurotransmitter release. NO is a candidate retrograde neurotransmitter which could determine both presynaptic current changes and LTP. NO cascade blockers inhibit both presynaptic current changes and LTP. The increase in intrinsic excitability involves a raise in apparent input resistance in the subthreshold region and a spike threshold reduction. Together with other forms of cerebellar plasticity, mf-GrC LTP opens new hypothesis on how the cerebellum processes incoming information.

Animals↗

Electrophysiological and behavioral effects of ethanol on crayfish.

The effects of EtOH on the crayfish Procambarus clarkii and P. simulans were examined behaviorally in vivo and electrophysiologically in vitro on pre- and postjunctional mechanisms of synaptic plasticity at opener excitor nerve-muscle junctions. Addition of 75 mM EtOH to the bath water of holding tanks produced 47 to 54 mM EtOH levels in the hemolymph (blood) within 24 hr. These hemolymph EtOH levels were maintained for weeks by daily changes of the bath water containing 75 mM EtOH. After 24 hr of exposure to 75 to 150 mM EtOH in vivo, crayfish showed behavioral signs of intoxication as measured by a significant increase in righting reflex times and a significant decrease in tail-flip escape behavior. After 2 weeks of chronic exposure to 75 mM EtOH, crayfish showed behavioral tolerance as measured by a decrease in righting time and an increase in tail-flip escape behavior to control levels. EtOH applied acutely to opener nerve-muscle preparations in vitro at 10 to 100 mM concentrations produced an increased probability of transmitter release as measured by an increased frequency of spontaneous release of transmitter quanta and an increased amplitude of facilitated synaptic potentials evoked by 10 to 40 Hz stimulation of the excitor axon. Acute application of 300 to 600 mM EtOH resulted in a decreased amplitude of facilitated synaptic potentials due primarily to a decrease in postsynaptic input resistance. These data suggest that EtOH has a concentration-dependent biphasic effect on synaptic transmission.

Animals↗

Synaptic efficacy is commonly regulated within a nervous system and predicts individual differences in learning.

The hypothesis that an individual's capacity for learning might be predicted or influenced by basal levels of synaptic efficacy has eluded empirical tests, owing in part to the inability to compare between animals single identified synaptic responses in the mammalian brain. To overcome this limitation, we have focused our analysis on the invertebrate Hermissenda, whose nervous system is composed of identifiable cells and synaptic interactions. Hermissenda were exposed to paired presentations of light and rotation such that the light came to elicit a learned defensive motor response. An animal's rate of learning was strongly correlated with the amplitude of the synaptic potential evoked in that animal's visual (light sensitive) receptors in response to stimulation of presynaptic vestibular (rotation sensitive) hair cells. In naive animals, strong correlations between the amplitude of both inhibitory and excitatory synaptic potentials were observed between synapses distributed throughout an animal's nervous system, and this conservation of synaptic efficacy was largely attributable to a common influence on transmitter release. These observations suggest that basal synaptic efficacy may be uniformly regulated throughout a nervous system, and provide direct evidence that the basal efficacy of synaptic transmission predicts, and possibly contributes to, individual differences between animals in their capacity to learn.

Action Potentials↗

Spatial patterns of excitation and inhibition evoked by lateral connectivity in layer 2/3 of rat barrel cortex.

In the rat barrel cortex, neurons in layer 4 are topographically arranged in a precise columnar structure, and the excitatory feed-forward input from layer 4 to layer 2/3 projects almost exclusively within the home barrel column. Here we analyzed the lateral connectivity that links neighboring columns in layer 2/3, which is necessary for integrating information across whiskers. We examined the spatial distributions of three different functional types of lateral connections in layer 2/3 of the rat barrel cortex: glutamate receptor-mediated excitatory connections, GABA(A) receptor-mediated inhibitory connections and GABA(B) receptor-mediated inhibitory connections. Synaptic potentials of pyramidal neurons, which are measures of the strength of connections, were evoked by a horizontal array of stimulation electrodes. The synaptic potentials and their decrease with distance from the stimulation site were measured in two types of slices whose planes were parallel to or orthogonal to barrel rows. Excitatory and GABA(B) receptor-mediated inhibitory connections were stronger along barrel rows than across them, whereas GABA(A) receptor-mediated inhibitory connections did not show such a tendency. These results indicate that lateral connectivity in layer 2/3 varies on the basis of not only excitatory polarity but also receptor subtypes.

Animals↗

Network stability through homeostatic scaling of excitatory and inhibitory synapses following inactivity in CA3 of rat organotypic hippocampal slice cultures.

Homeostatic plasticity is a phenomenon whereby synaptic strength is scaled in the context of the activity that the network receives. Here, we have analysed excitatory and inhibitory synapses in a model of homeostatic plasticity where rat organotypic hippocampal slice cultures were deprived of excitatory synaptic input by the NMDA and AMPA/KA glutamate receptor antagonists, AP5 and CNQX. We show that chronic excitatory synapse deprivation generates an excitable CA3 network where enhanced amplitude and frequency of spontaneous excitatory post-synaptic potentials were associated with increased glutamate receptor subunit expression and increased number and size of synapsin 1 and VGLUT1 positive puncta. Intact spontaneous inhibitory post-synaptic potentials coincided with persistent expression of the GABA-A receptor alpha subunit and GAD65 and an enhancement of parvalbumin-positive puncta. In this model of homeostatic plasticity, scaling up of synaptic excitation and maintenance of fast synaptic inhibition promote an excitable, but stable, CA3 network.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Dopamine-mediated actions of ephedrine in the rat substantia nigra.

Although ephedrine is a centrally active stimulant, its effect on midbrain dopamine neurons is not known. To study the effect of ephedrine on dopamine-containing cells, current-clamp microelectrode recordings were made from substantia nigra pars compacta (SNC) neurons in horizontal brain slice preparations. Ephedrine (100-1000 microM) slowed spontaneous firing and produced a modest concentration-dependent hyperpolarization of membrane potential (EC50 279 microM), with a concomitant net decrease in membrane resistance. These effects were blocked by the D2-like dopamine antagonist sulpiride (1 microM). Electrically evoked inhibitory synaptic potentials mediated by GABAB receptors were reduced 28% by ephedrine. However, ephedrine did not reduce fast synaptic potentials mediated by GABAA or ionotropic glutamate receptors. Inhibition of the GABAB response appeared to be mediated by a postsynaptic mechanism because ephedrine also reduced baclofen-induced hyperpolarization by 28%. Both ephedrine-induced hyperpolarization and inhibition of baclofen-induced hyperpolarization were abolished when slices were superfused with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). Despite perfusion with AMPT, the ability of ephedrine to cause hyperpolarization was restored after perfusing the slice with dopamine (30 microM). Taken together, these results suggest that ephedrine causes hyperpolarization and suppresses GABAB receptor-mediated effects by releasing endogenous dopamine. However, the high concentrations required to observe these effects in vitro suggest that biologically relevant central effects of ephedrine are more likely to be mediated either by non-dopamine systems, such as those involving noradrenaline, or by dopamine systems outside the SNC.

Action Potentials↗

Imaging of 4-AP-induced, GABA(A)-dependent spontaneous synchronized activity mediated by the hippocampal interneuron network.

Under conditions of increased excitability, such as application of the K(+) channel blocker 4-aminopyridine (4-AP, 100 microM), interneurons in the hippocampal slice show an additional form of synchronized activity that is distinct from the ictal and interictal epileptiform activity induced by these manipulations. In principal neurons, i.e., pyramidal and granule cells, this synchronized interneuron activity (SIA) generates large, multi-component synaptic potentials, which have been termed long-lasting depolarizations (LLDs). These LLDs are dependent on GABA(A) receptor-mediated synaptic transmission but not on excitatory amino acid (EAA) receptors. Intracellular recordings from hilar interneurons have shown that depolarizing GABA(A) receptor-mediated synaptic potentials are also largely responsible for the synchronization of interneurons. The spatiotemporal characteristics of this interneuron activity have not been investigated previously. Using a voltage-sensitive dye and optical techniques that are capable of recording spontaneous synchronized activity, we have characterized the spatiotemporal pattern of SIA (in the presence of 4-AP + EAA receptor antagonists) and compared it with interictal epileptiform activity (in 4-AP only). Like interictal activity, SIA could be observed throughout the hippocampal slice. Unlike interictal activity, which originated in area CA2/CA3 and spread from there, SIA was most prominent in area CA1 and originated either there or in the subiculum. In CA1, interictal activity was largest in and near stratum pyramidale, while SIA was mainly located in s. lacunosum moleculare. Furthermore SIA was equally likely to propagate in either direction, and multiple patterns of propagation could be observed within a single brain slice. These studies suggest that hippocampal area CA1 has the highest propensity for SIA, that multiple locations can serve as the site of origin, and that interneurons located in s. lacunosum moleculare or interneurons that specifically project to this region may be particularly important for synchronized interneuron activity.

2-Amino-5-phosphonovalerate↗

Activators of protein kinase C increase the phosphorylation of the synapsins at sites phosphorylated by cAMP-dependent and Ca2+/calmodulin-dependent protein kinase in the rat hippocampal slice.

Previous studies have shown that activators of protein kinase C (C kinase) produce synaptic potentiation in the hippocampus. For example, the C kinase activator phorbol dibutyrate has been shown to increase transmitter release in the hippocampus. In addition, a role for C kinase in long-term potentiation has been proposed. A common assumption in such studies has been that substrates for C kinase were responsible for producing these forms of synaptic potentiation. However, we have recently shown that phorbol dibutyrate increased the phosphorylated of synapsin II (formerly protein III, Browning et al., 1987) in chromaffin cells (Haycock et al., 1988). Synapsin II is a synaptic vesicle-associated phosphoprotein that is a very poor substrate for C kinase but an excellent substrate for cAMP-dependent and Ca2+/calmodulin-dependent protein kinase. We felt, therefore, that activation of C kinase might lead to activation of a kinase cascade. Thus effects of C kinase activation might be produced via the phosphorylation of proteins that are not substrates for C kinase. In this report we test the hypothesis that activators of C kinase increase the phosphorylation of synapsin II and an homologous protein synapsin I. Our data indicate that PdBu produced dose-dependent increases in the phosphorylation of synapsin I and synapsin II. We also performed phospho-site analysis of synapsin I using limited proteolysis. These studies indicated that PdBu increased the phosphorylation of multiple sites on synapsin I. These sites have previously been shown to be phosphorylated by both cAMP-dependent protein kinase and the multifunctional Ca2+/calmodulin-dependent protein kinase II.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Facilitation, augmentation, and potentiation of synaptic transmission at the superior cervical ganglion of the rabbit.

The effect of repetitive stimulation on synaptic transmission was studied in the isolated superior cervical ganglion of the rabbit under conditions of reduced quantal content. Excitatory postsynaptic potentials (EPSP) were recorded with the sucrose gap technique to obtain estimates of transmitter release. Four components of increased transmitter release, with time constants of decay similar to those observed at the frog neuromuscular junction at 20 degrees C, were found in the ganglion at 34 degrees C: a first component of facilitation, which decayed with a time constant of 59 +/- 14 ms (mean +/- SD); a second component of facilitation, which decayed with a time constant of 388 +/- 97 ms; augmentation, which decayed with a time constant of 7.2 +/- 1 s; and potentiation, which decayed with a time constant of 88 +/- 25 s. The addition of 0.1-0.2 mM Ba2+ to the Locke solution increased the magnitude but not the time constant of decay of augmentation. Ba2+ had little effect on potentiation. The addition of 0.2-0.8 mM Sr2+ to the Locke solution appeared to increase the magnitude of the second component of facilitation. Sr2+ had little effect on augmentation or potentiation. These selective effects of Ba2+ and Sr2+ on the components of increased transmitter release in the rabbit ganglion are similar to the effects of these ions at the frog neuromuscular junction. Although the effects of Ba2+ and Sr2+ are similar in the two preparations, the magnitudes of augmentation and the second component of facilitation after a single impulse were about 6-10 times greater in the rabbit ganglion than at the frog neuromuscular junction. These results suggest that the underlying mechanisms in the nerve terminal that give rise to the components of increased transmitter release in the rabbit ganglion and frog neuromuscular junction are similar but not identical.

Animals↗

Integration of nonphaselocked exteroceptive information in the control of rhythmic flight in the locust.

The integration of exteroceptive information in the flight control system of the locust was studied by determining the cellular basis of ocellar- (simple eye) mediated control of flight. Neural interactions that transform phase-independent sensory input into phase-specific motor output were characterized. Ocellar information about course deviations during flight was conveyed to the segmental thoracic ganglia by three pairs of large fast multimodal descending neurons. These made connections with thoracic motoneurons directly, via short-latency mono-or disynaptic pathways, and indirectly, via a population of intercalated thoracic interneurons. The synaptic potentials caused in the motoneurons by the direct pathway occurred at short latency and were adequate for summation with other types of sensory input. However, the strength of the synaptic effects of this pathway was weak compared with the central flight oscillator drive to the same motoneurons. In contrast, synaptic potentials evoked by the descending neurons in the thoracic interneurons were often large and brought these cells close to threshold. In turn, these interneurons always had stronger synaptic effects on postsynaptic flight motoneurons than did the descending neurons alone. We conclude that the indirect interneuronal pathway is more powerful in its effects on motoneurons than the direct pathway. Premotor thoracic interneurons, which received ocellar input appropriate for a role in correctional steering, were also rhythmically modulated during flight motor activity in phase with either depressor or elevator motoneurons. This phasic modulatory drive occurred in deafferented preparations, indicating that its source is the central oscillator for flight. Presentation of ocellar stimulation during flight motor activity showed that the central oscillatory modulation of the thoracic interneurons gated the transmission of sensory information through these interneurons. Ocellar-mediated postsynaptic potentials influenced the firing of thoracic interneurons only if they arrived during the proper phase of rhythmic drive. Thus the transmission of ocellar information from interneuron to motor neuron is possible only during appropriate phases of the flight cycle.

Animals↗

Electrophysiological properties and glucose responsiveness of guinea-pig ventromedial hypothalamic neurones in vitro.

The membrane properties of neurones in the guinea-pig ventromedial hypothalamic nucleus (v.m.h.) were studied in in vitro brain slice preparations. The average resting potential was -62.9 +/- 5.4 mV (mean +/- S.D.), input resistance was 155 +/- 58 M omega, and action potential amplitude was 69.9 +/- 6.3 mV. Three types of neurone were identified. The type A neurones were characterized by a short membrane time constant (7.3 +/- 2.0 ms) and a small after-hyperpolarization (a.h.p.) (2.0 +/- 1.2 mV) with a short half decay time of 67 +/- 55 ms after stimulation with a long outward current pulse. Type B had a long time constant (18.8 +/- 5.7 ms) and a large a.h.p. (6.9 +/- 2.4 mV) with a medium half decay time of 203 +/- 90 ms. Type C was characterized by a long time constant (14.3 +/- 2.3 ms) and a large a.h.p. (6.5 +/- 1.5 mV) with a long half decay time of 478 +/- 230 ms. The slopes of the frequency-current (f-I) plots of the three types were different, particularly for the first spike interval. The slopes for the type A (414 +/- 102 impulses s-1 nA-1) and type B neurones (480 +/- 120 impulses s-1 nA-1) were steeper than that for the type C neurones (178 +/- 41 impulses s-1 nA-1). This difference is probably related to the relatively long first interval observed in the type C neurones. In all type B and a few type C neurones, when the membrane potential was hyperpolarized beyond--65 mV the application of orthodromic or direct stimulation generated a burst of spikes, consisting of a low-threshold response (l.t.r.) of low amplitude and superimposed high-frequency spikes. At the original resting potential, outward current pulses produced a train of low-frequency spikes. In type C neurones maintained in a depolarized state (about -50 mV), inward current pulses produced a specific delay of the return to the original membrane potential. This delayed return was thought to be generated by activation of a transient K+ (IA) conductance. Stimulation at the lateral edge of the v.m.h. produced excitatory post-synaptic potentials (e.p.s.p.s) in type A neurones, e.p.s.p.s with l.t.r. in type B neurones and e.p.s.p.-inhibitory post-synaptic potential sequences in type C neurones. About 20% of v.m.h. neurones, particularly the type C cells, were depolarized by glucose application with an associated increase in the input membrane resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Long-term potentiation of synaptic transmission in the avian hippocampus.

The avian hippocampus plays a pivotal role in memory required for spatial navigation and food storing. Here we have examined synaptic transmission and plasticity within the hippocampal formation of the domestic chicken using an in vitro slice preparation. With the use of sharp microelectrodes we have shown that excitatory synaptic inputs in this structure are glutamatergic and activate both NMDA- and AMPA-type receptors on the postsynaptic membrane. In response to tetanic stimulation, the EPSP displayed a robust long-term potentiation (LTP) lasting >1 hr. This LTP was unaffected by blockade of NMDA receptors or chelation of postsynaptic calcium. Application of forskolin increased the EPSP and reduced paired-pulse facilitation (PPF), indicating an increase in release probability. In contrast, LTP was not associated with a change in the PPF ratio. Induction of LTP did not occlude the effects of forskolin. Thus, in contrast to NMDA receptor-independent LTP in the mammalian brain, LTP in the chicken hippocampus is not attributable to a change in the probability of transmitter release and does not require activation of adenylyl cyclase. These findings indicate that a novel form of synaptic plasticity might underlie learning in the avian hippocampus.

Adenylyl Cyclases↗

Common molecular pathways mediate long-term potentiation of synaptic excitation and slow synaptic inhibition.

Synaptic plasticity, the cellular correlate for learning and memory, involves signaling cascades in the dendritic spine. Extensive studies have shown that long-term potentiation (LTP) of the excitatory postsynaptic current (EPSC) through glutamate receptors is induced by activation of N-methyl-D-asparate receptor (NMDA-R)--the coincidence detector--and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Here we report that the same signaling pathway in the postsynaptic CA1 pyramidal neuron also causes LTP of the slow inhibitory postsynaptic current (sIPSC) mediated by metabotropic GABA(B) receptors (GABA(B)-Rs) and G protein-activated inwardly rectifying K(+) (GIRK) channels, both residing in dendritic spines as well as shafts. Indicative of intriguing differences in the regulatory mechanisms for excitatory and inhibitory synaptic plasticity, LTP of sIPSC but not EPSC was abolished in mice lacking Nova-2, a neuronal-specific RNA binding protein that is an autoimmune target in paraneoplastic opsoclonus myoclonus ataxia (POMA) patients with latent cancer, reduced inhibitory control of movements, and dementia.

Animals↗

Multiple interneuronal afferents to the giant cells in Aplysia.

1. Several different types of presynaptic neurones to the giant cells of Aplysia have been found in the pleural ganglion. Some of these presynaptic neurones are common to the left giant cell in the pleural ganglion and to the right giant cell in the abdominal ganglion but others make contact only with one. 2. Interneurones of the left giant cell were studied in detail. They can be identified not only physiologically from the type of post-synapitc potential (p.s.p.) which they produce in the left giant cell, but also by their localization in the ganglion. 3. Direct stimulation of these presynaptic neurones produced not only the classical types of post-synaptic potentials known as e.p.s.p. or i.p.s.p. but also a slow e.p.s.p. and more complex post-synaptic potentials consisting of a rapid depolarizing or hyperpolarizing component (e for excitatory; i for inhibitory). According the p.s.p.s. which have been found were classified as being of eight different types: e.p.s.p., slow e.p.s.p., pseudo-slow e.p.s.p., e.i.p.s.p., i.e.p.s.p., i.i.p.s.p., to which is added the biphasic p.s.p. (b.p.s.p.) of electrical origin. 4. The monosynaptic nature of each of these p.s.p.s. was established by four criteria: (a) ability to follow one to one the presynaptic spike, (b) short and constant latency, (c) change of p.s.p. with the presynaptic spike when the duration is prolonged by iontophoretic injection of TEA, (d) sensitivity of the synaptic efficacy to presynaptic polarization. 5. For all p.s.p.s., the hyperpolarization of the interneurone was followed by a decrease in the corresponding amplitude; on the contrary depolarization produced an increase in p.s.p. amplitude. 6. The physiological role of these p.s.p.s. and their possible mechanism are discussed.

Action Potentials↗