Abstract:Hippocampal pyramidal neurons often fire in bursts of action potentials with short interspike intervals (2-10 msec). These high-frequency bursts may play a critical role in the functional behavior of hippocampal neurons, but synaptic plasticity at such short times has not been carefully studied. To study synaptic modulation at very short time intervals, we applied pairs of stimuli with interpulse intervals ranging from 7 to 50 msec to CA1 synapses isolated by the method of minimal stimulation in hippocampal sl… Show more
“…Paired-pulse facilitation (PPF) is generally explained as an increase of release probability (P r ) during the second stimulus, arising from prior accumulation of residual Ca 2ϩ near active zones or a lingering effect of Ca 2ϩ on a Ca 2ϩ sensor (1,2). In contrast, paired-pulse depression (PPD) comes in multiple forms (3) and is open to a much wider range of possible explanations: receptor desensitization can be important in some cases (4) but is in general excluded. Instead, PPD is thought to originate presynaptically in most systems, as reflected by decreased transmitter output (5,6).…”
At central synapses, quantal size is generally regarded as fluctuating around a fixed mean with little change during short-term synaptic plasticity. We evoked quantal release by brief electric stimulation at single synapses visualized with FM 1-43 dye in hippocampal cultures. The majority of quantal events evoked at single synapses were monovesicular, based on examination of amplitude distribution of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-mediated responses. Consistent with previous findings, the quantal size did not change during paired-pulse facilitation (PPF), supporting the notion that the evoked events were monoquantal. However, during paired-pulse depression (PPD), there was a significant decrease in unitary quantal size, which was not due to postsynaptic receptor desensitization. This asymmetry of quantal modulation during PPF and PPD was demonstrated at the same single synapse at different extracellular calcium concentrations. Our results indicate that PPF can be fully accounted for by an increase of release probability, whereas PPD may be caused by decreases in both release probability and quantal size. One possible explanation is that the release of a quantum of neurotransmitter from synaptic vesicles is not invariant but subject to rapid calcium-dependent modulation during short-term synaptic plasticity.S hort-term synaptic plasticity is important for synaptic communication within the brain and is classically assessed with ''pairedpulse stimulation,'' two stimuli in close succession. There are various forms of paired-pulse modulation (PPM), typically attributed to different mechanisms. Paired-pulse facilitation (PPF) is generally explained as an increase of release probability (P r ) during the second stimulus, arising from prior accumulation of residual Ca 2ϩ near active zones or a lingering effect of Ca 2ϩ on a Ca 2ϩ sensor (1, 2). In contrast, paired-pulse depression (PPD) comes in multiple forms (3) and is open to a much wider range of possible explanations: receptor desensitization can be important in some cases (4) but is in general excluded. Instead, PPD is thought to originate presynaptically in most systems, as reflected by decreased transmitter output (5, 6). Reduced presynaptic release is most often attributed to vesicular depletion (7-11), but evidence for additional presynaptic mechanisms independent of vesicular depletion has also been provided (12-16).Deciphering PPM calls for a clear picture of quantal transmission at single synapses, but this is still under debate. Although general agreement has been reached about a lack of receptor saturation at excitatory synapses (17-19), controversy remains as to what generates variability in excitatory postsynaptic current (EPSC) size. One view is that single CNS synapses obey a ''one-vesicle rule,'' whereby presynaptic release is somehow capped at no more than one vesicle per presynaptic spike (8,(20)(21)(22)(23). The unitary evoked EPSC would then constitute a response to exocytosis of a single presynaptic vesicle, the ev...
“…Paired-pulse facilitation (PPF) is generally explained as an increase of release probability (P r ) during the second stimulus, arising from prior accumulation of residual Ca 2ϩ near active zones or a lingering effect of Ca 2ϩ on a Ca 2ϩ sensor (1,2). In contrast, paired-pulse depression (PPD) comes in multiple forms (3) and is open to a much wider range of possible explanations: receptor desensitization can be important in some cases (4) but is in general excluded. Instead, PPD is thought to originate presynaptically in most systems, as reflected by decreased transmitter output (5,6).…”
At central synapses, quantal size is generally regarded as fluctuating around a fixed mean with little change during short-term synaptic plasticity. We evoked quantal release by brief electric stimulation at single synapses visualized with FM 1-43 dye in hippocampal cultures. The majority of quantal events evoked at single synapses were monovesicular, based on examination of amplitude distribution of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-mediated responses. Consistent with previous findings, the quantal size did not change during paired-pulse facilitation (PPF), supporting the notion that the evoked events were monoquantal. However, during paired-pulse depression (PPD), there was a significant decrease in unitary quantal size, which was not due to postsynaptic receptor desensitization. This asymmetry of quantal modulation during PPF and PPD was demonstrated at the same single synapse at different extracellular calcium concentrations. Our results indicate that PPF can be fully accounted for by an increase of release probability, whereas PPD may be caused by decreases in both release probability and quantal size. One possible explanation is that the release of a quantum of neurotransmitter from synaptic vesicles is not invariant but subject to rapid calcium-dependent modulation during short-term synaptic plasticity.S hort-term synaptic plasticity is important for synaptic communication within the brain and is classically assessed with ''pairedpulse stimulation,'' two stimuli in close succession. There are various forms of paired-pulse modulation (PPM), typically attributed to different mechanisms. Paired-pulse facilitation (PPF) is generally explained as an increase of release probability (P r ) during the second stimulus, arising from prior accumulation of residual Ca 2ϩ near active zones or a lingering effect of Ca 2ϩ on a Ca 2ϩ sensor (1, 2). In contrast, paired-pulse depression (PPD) comes in multiple forms (3) and is open to a much wider range of possible explanations: receptor desensitization can be important in some cases (4) but is in general excluded. Instead, PPD is thought to originate presynaptically in most systems, as reflected by decreased transmitter output (5, 6). Reduced presynaptic release is most often attributed to vesicular depletion (7-11), but evidence for additional presynaptic mechanisms independent of vesicular depletion has also been provided (12-16).Deciphering PPM calls for a clear picture of quantal transmission at single synapses, but this is still under debate. Although general agreement has been reached about a lack of receptor saturation at excitatory synapses (17-19), controversy remains as to what generates variability in excitatory postsynaptic current (EPSC) size. One view is that single CNS synapses obey a ''one-vesicle rule,'' whereby presynaptic release is somehow capped at no more than one vesicle per presynaptic spike (8,(20)(21)(22)(23). The unitary evoked EPSC would then constitute a response to exocytosis of a single presynaptic vesicle, the ev...
“…APs have successfully evoked neurotransmitter release or not [1,3,[8][9][10]. Although it has been argued that RID is a selection effect caused by stochastic state-changes of the release machinery [11], previous work suggests that RID indeed has a distinct physiological basis [3].…”
Section: Introductionmentioning
confidence: 99%
“…Synapses show a broad range of activity-dependent adaptive behaviours [1][2][3][4]. Those that occur on the shortest time scales are known as short-term plasticity.…”
Section: Introductionmentioning
confidence: 99%
“…This AP propagates along the neuronal membrane until it reaches a nerve terminal, where it may evoke the release of one or more synaptic vesicles containing neurotransmitter. The neurotransmitter diffuses through the extracellular space, and may bind to the membranes of other neurons.Synapses show a broad range of activity-dependent adaptive behaviours [1][2][3][4]. Those that occur on the shortest time scales are known as short-term plasticity.…”
mentioning
confidence: 99%
“…We evoked stimulus sequences of APs in presynaptic cells under current clamp using short DC current pulses (5 ms, 1 nA), and recorded excitatory postsynaptic currents (EPSCs) from postsynaptic cells under voltage clamp. 1 We used constant rate and Poisson stimulus sequences, with characteristic frequencies of 5,10,20,30,35,40 or 50 Hz. Constant-rate stimuli consisted of either 6 or 20 pulses, and all sequences were followed by a recovery pulse after a delay of 400 or 500 ms.…”
Short-term changes in efficacy have been postulated to enhance the ability of synapses to transmit information between neurons, and within neuronal networks. Even at the level of connections between single neurons, direct confirmation of this simple conjecture has proven elusive. By combining paired-cell recordings, realistic synaptic modelling and information theory, we provide evidence that short-term plasticity can not only improve, but also reduce information transfer between neurons. We focus on a concrete example in rat neocortex, but our results may generalise to other systems. When information is contained in the timings of individual spikes, we find that facilitation, depression and recovery affect information transmission in proportion to their impacts upon the probability of neurotransmitter release.When information is instead conveyed by mean spike rate only, the influences of short-term plasticity critically depend on the range of spike frequencies that the target network can distinguish (its effective dynamic range). Our results suggest that to efficiently transmit information, the brain must match synaptic type, coding strategy and network connectivity during development and behaviour.
IntroductionThe primary means by which information moves about a brain or neural network is the recursive generation of action potentials (APs) in networks of synaptically connected neurons. How effectively information passes from one cell to another is seen in how much information the APs generated in a postsynaptic cell contain about the APs in the presynaptic cell. This is governed by the processes that lead APs in one cell to evoke APs in another. Here, we focus on the impact of the properties of the presynaptic terminal upon neuronal information transfer in neocortex.As basic network components, neurons consist of an excitable cell membrane along which an electrical signal can be carried, and synapses by which such an excitation in one cell can invoke or suppress similar excitations in nearby cells. An electric potential difference is maintained across the cell membrane by channel proteins that transport ions between the intracellular and extracellular solutions. This potential is altered by the opening or closing of ion channels in the cell membrane. Such potential changes may be caused by the binding of a neurotransmitter, which typically is emitted from nerve terminals, to the cell membrane. Changes in the membrane potential also trigger further alterations in the activation state of channels maintaining the potential itself, generating a localised inversion of the potential (an action potential). This AP propagates along the neuronal membrane until it reaches a nerve terminal, where it may evoke the release of one or more synaptic vesicles containing neurotransmitter. The neurotransmitter diffuses through the extracellular space, and may bind to the membranes of other neurons.Synapses show a broad range of activity-dependent adaptive behaviours [1][2][3][4]. Those that occur on the shortest time sca...
Neurotrophins are traditionally thought to be secretory proteins that regulate long-term survival and differentiation of neurons. Recent studies have revealed a previously unexpected role for neurotrophins in synaptic development and plasticity in diverse neuronal populations. In this review, we focus on the synaptic function of brain-derived neurotrophic factor (BDNF) in the hippocampus. Although a variety of in vitro experiments have shown the ability of BDNF to acutely modulate synaptic transmission, whether BDNF truly potentiates basal synaptic transmission in hippocampal neurons remains controversial. More consistent evidence has been obtained for the role of BDNF in long-term potentiation (LTP), a cellular model for learning and memory. BDNF also potentiates high frequency transmission by modulating the number of docked vesicles and the levels of the vesicle protein synaptobrevin and synaptophysin at the CA1 synapses. Both pre- and postsynaptic effects of BDNF have been demonstrated. Recent studies have begun to address the role of BDNF in late-phase LTP and in the development of hippocampal circuit. BDNF and other neurotrophins may represent a new class of neuromodulators that regulate neuronal connectivity and synaptic efficacy. J. Neurosci. Res. 58:76-87, 1999. Published 1999 Wiley-Liss, Inc.
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