Correlation of Transmitter Release with Membrane Properties of the Presynaptic Fiber of the Squid Giant Synapse

Depolarization of the presynaptic terminal by current produced a postsynaptic potential (PSP) which increased with increasing presynaptic polarization and then reached a plateau. Iontophoretic injection of tetraethylammonium ions (TEA) into the presynaptic axon near the terminal produced a prolonged presynaptic spike. The resulting PSP is increased in size and its time course closely followed that of the presynaptic spike. The presynaptic fiber no longer exhibited rectification and strong depolarizations revealed that the PSP reached a maximum with about 110 mv depolarization. Further depolarization produced a decrease in PSP amplitude and finally transmission was blocked. However, a PSP then always appeared on withdrawal of the depolarizing current. Under the conditions of these experiments, the PSP could be considered a direct measure of transmitter release. Bathing the TEA-injected synapse with concentrations of tetrodotoxin (TTX) sufficient to block spike activity in both pre- and postsynaptic axons did not greatly modify postsynaptic electrogenesis. However, doubling TTX concentration reversibly blocked PSP. Thus the permeability changes to Na and K accompanying the spike do not appear necessary for transmitter release. Some other processes related to the level of presynaptic polarization must be involved to explain the data. The inhibition of transmitter release by strong depolarizations appears to be related to Ca action. A membrane Ca current may also be necessary for normal transmitter release.     

Synaptic transmission in the sixth ganglion of the cockroach: action of 4-aminopyridine.

1. Study was made of the action of 4-aminopyridine (5 X 10(-5) M) on synaptic transmission in the last abdominal ganglion of Periplaneta americana. The 'oil-gap' technique was used to record postsynaptic events in a single giant axon. 2. 4-AP quickly increased the 'background' of postsynaptic activity, which consisted of 'spontaneous' unitary EPSPs and IPSPs. Postsynaptic spikes were also propagated. 3. Both evoked EPSPs (stimulation of cercal nerve XI) and evoked IPSPs (stimulation of cercal nerve X) were greatly increased in amplitude although their duration (half-time) was unaltered. 4. 4-AP triggered presynaptic action potentials in the cercal nerves (recorded with external electrodes). These 'antidromic' potentials appeared singly or sometimes repetitively, especially after electrical stimulation of the cercal nerves. They were often in monosynaptic correlation with unitary EPSPs. 5. Neither the resting potential nor the postsynaptic membrane resistance was modified. 6. There were no changes in the equilibrium potentials of the ions involved in postsynaptic events. 7. The results may be essentially explained by an increase in transmitter release after 4-AP treatment, which may be partly the result of a rise in presynaptic terminal excitability, and partly the result of a lengthening of the presynaptic action potentials.     

Computational Consequences of Temporally Asymmetric Learning Rules: I. Differential Hebbian Learning

Temporally asymetric learning rules governing plastic changes in synaptic efficacy have recently been identified in physiological studies. In these rules, the exact timing of pre- and postsynaptic spikes is critical to the induced change of synaptic efficacy. The temporal learning rules treated in this article are approximately antisymmetric; the synaptic efficacy is enhanced if the postsynaptic spike follows the presynaptic spike by a few milliseconds, but the efficacy is depressed if the postsynaptic spike precedes the presynaptic spike. The learning dynamics of this rule are studied using a stochastic model neuron receiving a set of serially delayed inputs. The average change of synaptic efficacy due to the temporally antisymmetric learning rule is shown to yield differential Hebbian learning. These results are demonstrated with both mathematical analyses and computer simulations, and connections with theories of classical conditioning are discussed.     

Synaptic interactions between nonspiking local interneurones in the terminal abdominal ganglion of the crayfish

Nonspiking local interneurones are the important premotor elements in arthropod motor control systems. We have analyzed the synaptic interactions between nonspiking interneurones in the crayfish terminal (6th) abdominal ganglion using simultaneous intracellular recordings. Only 15% of nonspiking interneurones formed bi-directional excitatory connections. In 77% of connections, however, the nonspiking interneurones showed a one-way inhibitory interaction. In these cases, the presynaptic nonspiking interneurones received excitatory synaptic inputs from the sensory afferents innervating hairs on the surface of the uropods and the postsynaptic nonspiking interneurones received inhibitory synaptic inputs that were partly mediated by the inputs to the presynaptic nonspiking interneurones. The membrane hyperpolarization of the postsynaptic nonspiking interneurones mediated by the presynaptic nonspiking interneurones was reduced in amplitude when the hyperpolarizing current was injected into the postsynaptic interneurones, or when the external bathing solution was replaced with one containing low calcium and high magnesium concentrations. The role of these interactions in the circuits controlling the movements of the terminal appendages is discussed.Abbreviations AL antero-lateral - epsp excitatory postsynaptic potential - ipsp inhibitory postsynaptic potential - PL postero-lateral     

Effects of temperan a central synapse between identified motor neurons in the locust

Summary Changing the temperature from 10–40 °C modifies the transmission at an established monosynaptic connection between the fast extensor tibiae (FETi) and flexor tibiae motor neurons in the metathoracic ganglion of the locustSchistocerca gregaria (Forskål). Striking changes occur to the shape of the spikes, to membrane resistance, to the synaptic delay, and to the evoked synaptic potentials.In the presynaptic FETi motor neuron, raising the temperature reduces the amplitude of an antidromic spike recorded in the soma by a factor of 10 (40 mV to 4 mV), reduces the time taken to reach peak amplitude by 5 (3.5 to 0.7 ms) and decreases the duration at half maximum amplitude by 0.5. The conduction velocity of the spike in the axon is increased by 50% from 10 °C to 40 °C. Orthodromic spikes are affected by temperature in a similar way to the antidromic spikes.The membrane resistance of both pre- and postsynaptic motor neurons falls as the temperature is raised. The membrane resistance of FETi falls by a factor of 4 (about 4 M at 10 °C to 1 M at 40 °C). A contributory component to this fall could be the increase in the frequency of synaptic potentials generated as a result of inputs from other neurons. No temperature dependence could be demonstrated on the voltage threshold relative to resting potential for evoking orthodromic spikes, but because the resistance changes, the current needed to achieve this voltage must be increased at higher temperatures.The latency measured from the peak of the spike in the soma of FETi to the start of the EPSP in the soma of a flexor motor neuron decreases by a factor of 20 (10 ms at 10 °C to 0.5 ms at 40 °C).In a postsynaptic flexor tibiae motor neuron, the amplitude of the evoked synaptic potential increases by a factor of 3.4 (5 mV to 17 mV), its duration at half maximum amplitude decreases by 3 (7 ms at 12 °C to 2.3 ms at 32 °C) and its rate of rise increases by 3. An increased likelihood that spikes will occur in the flexor contributes to the enhanced amplitude of the compound EPSP at temperatures above 20 °C.Abbreviation FETi fast extensor tibiae motor neuron     

Intracellular recording from the giant synapse of the squid

1. Recording with glass micropipette electrodes inserted close to the synaptic region, in the presynaptic and in the postsynaptic fibers of the giant synapse in the stellate ganglion of the squid, has been accomplished. 2. The forms of the spike and of the synaptic potential are very much like those reported earlier (Bullock, 1948) from macroelectrodes. The crest time and the rate of fall are labile and depend on the state of fatigue, though the time of initiation of the postsynaptic potential does not. 3. It is concluded after examination of both intra- and extracellular recordings that there is a real synaptic delay of the order of 1 or 2 milliseconds at 15–20°C. 4. There is sometimes a very small and sometimes no visible deflection in the intracellular postsynaptic record attributable to the presynaptic spike. It is concluded that transmission cannot be electrical. 5. The amplitude of the postsynaptic potential can be controlled over some range by the amplitude of the presynaptic potential. 6. Hyperpolarization of the postsynaptic membrane results in increase in amplitude of spikes up to 200 millivolts, in increase in the membrane potential level at which the spike flares up, but in no considerable change in the amplitude in postsynaptic potential. 7. The postsynaptic potential can add to the late falling phase and the undershoot of an antidromic spike in the postfiber but cannot add to the crest or early part of the falling phase. The earliest part of the antidromic spike during which the postsynaptic potential can add is probably a period of refractoriness to electrical shock by analogy with the properties of the axon.     

Electron microscope observations on synaptic vesicles in synapses of the retinal rods and cones

The submicroscopic organization of the rod and cone synapses of the albino rabbit has been investigated with the use of the electron microscope. The most common rod synapse consists of an enlarged expansion of the rod fiber (the so called spherule) into which the dendritic postsynaptic fiber of the bipolar cell penetrates and digitates. The membrane surrounding the terminal consists of a double layer, the external of which is interpreted as belonging to the intervening glial cells. The synaptic membrane has a pre- and a postsynaptic layer with a total thickness of 180 to 300 A. The presynaptic layer is frequently denser and is intimately associated with the adjacent synaptic vesicles. The synaptic membrane shows processes constituted by foldings of the presynaptic layer. The entire spherule is filled with synaptic vesicles varying in diameter between 200 and 650 A with a mean of 386 A. In addition, the spherule contains a few large vacuoles near the rod fiber, interpreted as endoplasmic reticulum, and a matrix in which with high resolution a fine filamentous material can be observed. The postsynaptic fiber is homogeneous and usually does not show synaptic vesicles. In animals maintained in complete darkness for 24 hours vesicles appear to accumulate near the synaptic membrane and its processes. After 9 days there is a sharp decrease in size of the synaptic vesicles. A special rod synapse in which the dendritic postsynaptic expansion penetrates directly into the rod cell body has been identified. In line with Cajal's classification this type of synapse could be considered as a somatodendritic one. The cone synapse has a much larger terminal with a more complex relationship with the postsynaptic fiber. However, the same components recognized in the rod synapse can be observed. In animals maintained for 9 days in complete darkness there is also a considerable diminution in size of the synaptic vesicles.     

Electrical Changes in Pre- and Postsynaptic Axons of the Giant Synapse of Loligo

Potential changes both in pre- and postsynaptic axons were recorded from the giant synapse of squid with intracellular electrodes. Synaptic current was also recorded by a voltage clamp method. Facilitation of postsynaptic potential caused by applying two stimuli several milliseconds apart was accompanied by an increase in the amplitude of the presynaptic action potential. Depression of the postsynaptic potential occurred without changes in the presynaptic action potential. Increase in the concentration of Ca in sea water caused an increase in amplitude of the synaptic current. On the other hand increase in Mg concentration decreased the amplitude of the synaptic current. In these cases no appreciable change in the presynaptic action potential was observed. Extracellularly recorded potential changes of the presynaptic axon showed mainly a positive deflexion at the synaptic region and a negative deflexion in the more proximal part of the presynaptic axon. Mechanism of synaptic transmission is discussed.     

Modulation of transmitter release by presynaptic resting potential and background calcium levels

Activation of presynaptic ion channels alters the membrane potential of nerve terminals, leading to changes in transmitter release. To study the relationship between resting potential and exocytosis, we combined pre- and postsynaptic electrophysiological recordings with presynaptic Ca(2+) measurements at the calyx of Held. Depolarization of the membrane potential to between -60 mV and -65 mV elicited P/Q-type Ca(2+) currents of < 1 pA and increased intraterminal Ca(2+) by < 100 nM. These small Ca(2+) elevations were sufficient to enhance the probability of transmitter release up to 2-fold, with no effect on the readily releasable pool of vesicles. Moreover, the effects of mild depolarization on release had slow kinetics and were abolished by 1 mM intraterminal EGTA, suggesting that Ca(2+) acted through a high-affinity binding site. Together, these studies suggest that control of resting potential is a powerful means for regulating synaptic function at mammalian synapses.     

Effects of rectification on synaptic efficacy.

We have investigated the effects of postsynaptic membrane properties on the shape of synaptic potentials generated by time-varying synaptic conductances. We used numerical simulation techniques to model cells of several different geometrical forms, from an isopotential sphere to a neuron with a soma and a dendritic tree. A variety of postsynaptic membrane properties were tested: (a) a passive resistance-capacitance membrane, (b) a membrane represented by the Hodgkin and Huxley (HH) equations, and (c) a membrane that was passive except for a delayed rectification represented by a voltage- and time-dependent increase in GK. In all cases we investigated the effects of these postsynaptic membrane properties on synaptic potentials produced by synaptic conductances that were fast or slow compared with the membrane time constant. In all cases the effects of postsynaptic rectification occurred on postsynaptic potentials of amplitudes as low as 1 mV. The HH model (compared with the passive model) produced an increased peak amplitude (from the increase in GNa) but a decreased half-width and a decreased time integral (from the increase in GK). These effects of the HH GK change were duplicated by a simple analytical rectifier model.     

Long-lasting synaptic potentials and the modulation of synaptic transmission.

Long-lasting postsynaptic potentials (PSPs) generated by decreases in membrane conductance (permeability) have been reported in many types of neurons. We investigated the possible role of such long-lasting decreases in membrane conductance in the modulation of synaptic transmission in the sympathetic ganglion of the bullfrog. The molecular basis by which such conductance-decrease PSPs are generated was also investigated. Synaptic activation of muscarinic cholinergic receptors on these sympathetic neurons results in the generation of a slow EPSP (excitatory postsynaptic potential), which is accompanied by a decrease in membrane conductance. We found that the conventional "fast" EPSPs were increased in amplitude and duration during the iontophoretic application of methacholine, which activates the muscarinic postsynaptic receptors. A similar result was obtained when a noncholinergic conductance-decrease PSP--the late-slow EPSP--was elicited by stimulation of a separate synaptic pathway. The enhancement of fast EPSP amplitude increased the probability of postsynaptic action potential generation, thus increasing the efficacy of impulse transmission across the synapse. Stimulation of one synaptic pathway is therefore capable of increasing the efficacy of synaptic transmission in a second synaptic pathway by a postsynaptic mechanism. Furthermore, this enhancement of synaptic efficacy is long-lasting by virtue of the long duration of the slow PSP. Biochemical and electrophysiological techniques were used to investigate whether cyclic nucleotides are intracellular second messengers mediating the membrane permeability changes underlying slow-PSP generation. Stimulation of the synaptic inputs, which lead to the generation of the slow-PSPs, increased the ganglionic content of both cyclic AMP and cyclic GMP. However, electrophysiological analysis of the actions of these cyclic nucleotides and the actions of agents that affect their metabolism does not provide support for such a second messenger role for either cyclic nucleotide.     

Impact of fast sodium channel inactivation on spike threshold dynamics and synaptic integration

Neurons spike when their membrane potential exceeds a threshold value. In central neurons, the spike threshold is not constant but depends on the stimulation. Thus, input-output properties of neurons depend both on the effect of presynaptic spikes on the membrane potential and on the dynamics of the spike threshold. Among the possible mechanisms that may modulate the threshold, one strong candidate is Na channel inactivation, because it specifically impacts spike initiation without affecting the membrane potential. We collected voltage-clamp data from the literature and we found, based on a theoretical criterion, that the properties of Na inactivation could indeed cause substantial threshold variability by itself. By analyzing simple neuron models with fast Na inactivation (one channel subtype), we found that the spike threshold is correlated with the mean membrane potential and negatively correlated with the preceding depolarization slope, consistent with experiments. We then analyzed the impact of threshold dynamics on synaptic integration. The difference between the postsynaptic potential (PSP) and the dynamic threshold in response to a presynaptic spike defines an effective PSP. When the neuron is sufficiently depolarized, this effective PSP is briefer than the PSP. This mechanism regulates the temporal window of synaptic integration in an adaptive way. Finally, we discuss the role of other potential mechanisms. Distal spike initiation, channel noise and Na activation dynamics cannot account for the observed negative slope-threshold relationship, while adaptive conductances (e.g. K+) and Na inactivation can. We conclude that Na inactivation is a metabolically efficient mechanism to control the temporal resolution of synaptic integration.     

Pre- and postsynaptically expressed spike-timing-dependent plasticity contribute differentially to neuronal learning

A plethora of experimental studies have shown that long-term synaptic plasticity can be expressed pre- or postsynaptically depending on a range of factors such as developmental stage, synapse type, and activity patterns. The functional consequences of this diversity are not clear, although it is understood that whereas postsynaptic expression of plasticity predominantly affects synaptic response amplitude, presynaptic expression alters both synaptic response amplitude and short-term dynamics. In most models of neuronal learning, long-term synaptic plasticity is implemented as changes in connective weights. The consideration of long-term plasticity as a fixed change in amplitude corresponds more closely to post- than to presynaptic expression, which means theoretical outcomes based on this choice of implementation may have a postsynaptic bias. To explore the functional implications of the diversity of expression of long-term synaptic plasticity, we adapted a model of long-term plasticity, more specifically spike-timing-dependent plasticity (STDP), such that it was expressed either independently pre- or postsynaptically, or in a mixture of both ways. We compared pair-based standard STDP models and a biologically tuned triplet STDP model, and investigated the outcomes in a minimal setting, using two different learning schemes: in the first, inputs were triggered at different latencies, and in the second a subset of inputs were temporally correlated. We found that presynaptic changes adjusted the speed of learning, while postsynaptic expression was more efficient at regulating spike timing and frequency. When combining both expression loci, postsynaptic changes amplified the response range, while presynaptic plasticity allowed control over postsynaptic firing rates, potentially providing a form of activity homeostasis. Our findings highlight how the seemingly innocuous choice of implementing synaptic plasticity by single weight modification may unwittingly introduce a postsynaptic bias in modelling outcomes. We conclude that pre- and postsynaptically expressed plasticity are not interchangeable, but enable complimentary functions.     

Local learning rules: predicted influence of dendritic location on synaptic modification in spike-timing-dependent plasticity

Recent indirect experimental evidence suggests that synaptic plasticity changes along the dendrites of a neuron. Here we present a synaptic plasticity rule which is controlled by the properties of the pre- and postsynaptic signals. Using recorded membrane traces of back-propagating and dendritic spikes we demonstrate that LTP and LTD will depend specifically on the shape of the postsynaptic depolarization at a given dendritic site. We find that asymmetrical spike-timing-dependent plasticity (STDP) can be replaced by temporally symmetrical plasticity within physiologically relevant time windows if the postsynaptic depolarization rises shallow. Presynaptically the rule depends on the NMDA channel characteristic, and the model predicts that an increase in Mg²⁺ will attenuate the STDP curve without changing its shape. Furthermore, the model suggests that the profile of LTD should be governed by the postsynaptic signal while that of LTP mainly depends on the presynaptic signal shape.     

A wide-acting peptidergic interneurone in the snail Helix pomatia : Graded recruitment and local firing of terminal processes

Simultaneous pre- and postsynaptic intracellular recordings were used to study the mechanism of presynaptic terminal recruitment in a multifunction interneurone in the snail Helix pomatia. The interneurone was presynaptic to at least 20 neurones. The synaptic efficiency was correlated with the presence of presynaptic depolarizing after-potentials (DAPs) electrotonically produced by the delayed firing of remote terminal processes. These processes have large swellings filled with neurosecretory vesicles. The terminals were recruited in a graded manner when the interneurone was fired with a prolonged current. The terminal recruitment was enhanced by stimulating various efferent nerves, which presumably activated presynaptic receptors for dopamine. A few animals (three out of 300) had two electrically coupled interneurones. Simultaneous recordings from both cells showed that the terminals could be fired independently of the soma-axon activity. The graded and local firing of the presynaptic terminals was attributed to the electrical load that the large boutons exert on electrotonically spreading presynaptic impulses.     

Non-Decaying postsynaptics potentials and delayed spikes in hippocampal pyramidal neurons generated by a zero slope conductance created by the persistent Na+ current

The negative slope conductance created by the persistent sodium current (I_NaP) prolongs the decay phase of excitatory postsynaptic potentials (EPSPs). In a recent study, we demonstrated that this effect was due to an increase of the membrane time constant. When the negative slope conductance opposes completely the positive slope conductances of the other currents it creates a zero slope conductance region. In this region the membrane time constant is infinite and the decay phase of the EPSPs is virtually absent. Here we show that non-decaying EPSPs are present in CA1 hippocampal pyramidal cells in the zero slope conductance region, in the suprathreshold range of membrane potential. Na⁺ channel block with tetrodotoxin abolishes the non-decaying EPSPs. Interestingly, the non-decaying EPSPs are observed only in response to artificial excitatory postsynaptic currents (aEPSCs) of small amplitude, and not in response to aEPSCs of big amplitude. We also observed concomitantly delayed spikes with long latencies and high variability only in response to small amplitude aEPSCs. Our results showed that in CA1 pyramidal neurons I_NaP creates non-decaying EPSPs and delayed spikes in the subthreshold range of membrane potentials, which could potentiate synaptic integration of synaptic potentials coming from distal regions of the dendritic tree.     

Influence of ionic environment on the relationship between pre- and postsynaptic potentials

The effects of various ions on the relationship between pre- and postsynaptic potentials were studied using untreated squid giant synapses, or those injected presynaptically with tetraethylammonium ions (TEA) in the presence of 10^?6 g/ml tetrodotoxin (TTX). The synaptic transfer function was, in general, augmented by increasing [Ca²⁺]₀ or by reducing [Mg²⁺]₀. Opposite results were found by lowering either [Na⁺]₀ or [Ca²⁺]₀, or by increasing [K⁺]₀ or [Mg²⁺]₀. When [Ca²⁺]₀ was removed, presynaptically applied depolarizations failed to produce both “On-” and “Off-PSP's.” Electrophoretically injected Ca²⁺ into the presynaptic terminal reduced synaptic transmission. The minimal level of presynaptic membrane potential produced by an applied outward current pulse, which suppressed On-PSP completely, averaged 106 mV inside positive (ranging between 52–205 mV from 12 preparations). The potential level was shifted more negatively on lowering [Ca²⁺]₀ and more positively in high [Ca²⁺]₀-media. However, altering the [Na⁺]₀ did not change the suppression level appreciably. Under these ionic circumstances the maximum amplitude of On-PSP, as well as Off-PSP, was markedly changed, but the level of the presynaptic depolarization required to evoke a maximum On-PSP appeared to be unchanged, and the average value was 50 mV from the resting membrane potential level. Although the data are only qualitative, they appear to support the “Ca hypothesis” for the transmitter release and its shut-off mechanism. Replacement of 423 mM Cl^? by Br^? or with isethionate did not affect synaptic transmission.     

Retrograde regualtion of presynaptic development during synaptogenesis

Major advances are occurring in our understanding of the events leading to synapse formation. Contact between the growth cone and target tissu leads to intercellular signaling which controls both pre- and postsynaptic development of the synapse. The identity of retrograde signals that regualte presynaptic development are beginning to emerge, and the signal transduction cascades that are activated presynaptically are being characterized. Recent studies have shown that both the resting calcium level and activation of presynatptic protein kinase A are critical in the development of the presynaptic terminal. An understanding of these regulatory mechanisms is be ginning to provide insight into the molecular control of synaptic specificity. 1994 John Wiley & Sons, Inc.     

Dendritic Spikes Amplify the Synaptic Signal to Enhance Detection of Motion in a Simulation of the Direction-Selective Ganglion Cell

The On-Off direction-selective ganglion cell (DSGC) in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials) are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS) in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell''s dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within cortical circuitry.     

Spike-timing dependent synaptic plasticity: a phenomenological framework

 In this paper a phenomenological model of spike-timing dependent synaptic plasticity (STDP) is developed that is based on a Volterra series-like expansion. Synaptic weight changes as a function of the relative timing of pre- and postsynaptic spikes are described by integral kernels that can easily be inferred from experimental data. The resulting weight dynamics can be stated in terms of statistical properties of pre- and postsynaptic spike trains. Generalizations to neurons that fire two different types of action potentials, such as cerebellar Purkinje cells where synaptic plasticity depends on correlations in two distinct presynaptic fibers, are discussed. We show that synaptic plasticity, together with strictly local bounds for the weights, can result in synaptic competition that is required for any form of pattern formation. This is illustrated by a concrete example where a single neuron equipped with STDP can selectively strengthen those synapses with presynaptic neurons that reliably deliver precisely timed spikes at the expense of other synapses which transmit spikes with a broad temporal distribution. Such a mechanism may be of vital importance for any neuronal system where information is coded in the timing of individual action potentials. Received: 23 January 2002 / Accepted: 28 March 2002 Correspondence to: W.M. Kistler (e-mail: kistler@anat.fgg.eur.nl Fax: +31 10 408 5459)