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1.
Postsynaptic signaling and plasticity mechanisms 总被引：1，自引：0，他引：1
In excitatory synapses of the brain, specific receptors in the postsynaptic membrane lie ready to respond to the release of the neurotransmitter glutamate from the presynaptic terminal. Upon stimulation, these glutamate receptors activate multiple biochemical pathways that transduce signals into the postsynaptic neuron. Different kinds of synaptic activity elicit different patterns of postsynaptic signals that lead to short- or long-lasting strengthening or weakening of synaptic transmission. The complex molecular mechanisms that underlie postsynaptic signaling and plasticity are beginning to emerge. 相似文献
2.
In a variety of vertebrates and invertebrates, long-lasting enhancement of synaptic transmission contributes to the storage of memory lasting one or more days. However, it has not been demonstrated directly whether this increase in synaptic transmission is caused by an enhancement of transmitter release or an increase in the sensitivity of the postsynaptic receptors. These possibilities can be distinguished by a quantal analysis in which the size of the miniature excitatory postsynaptic potential released spontaneously from the presynaptic terminal is used as a reference. By means of microcultures, in which single sensory and motor neurons of Aplysia were plated together, miniature excitatory postsynaptic potentials attributable to the spontaneous release of single transmitter quanta from individual presynaptic neurons were recorded and used to analyze long-term facilitation induced by repeated applications of 5-hydroxytryptamine. The results indicate that the facilitation is caused by an increase in the number of transmitter quanta released by the presynaptic neuron. 相似文献
3.
Heine M Groc L Frischknecht R Béïque JC Lounis B Rumbaugh G Huganir RL Cognet L Choquet D 《Science (New York, N.Y.)》2008,320(5873):201-205
AMPA glutamate receptors (AMPARs) mediate fast excitatory synaptic transmission. Upon fast consecutive synaptic stimulation, transmission can be depressed. Recuperation from fast synaptic depression has been attributed solely to recovery of transmitter release and/or AMPAR desensitization. We show that AMPAR lateral diffusion, observed in both intact hippocampi and cultured neurons, allows fast exchange of desensitized receptors with na?ve functional ones within or near the postsynaptic density. Recovery from depression in the tens of millisecond time range can be explained in part by this fast receptor exchange. Preventing AMPAR surface movements through cross-linking, endogenous clustering, or calcium rise all slow recovery from depression. Physiological regulation of postsynaptic receptor mobility affects the fidelity of synaptic transmission by shaping the frequency dependence of synaptic responses. 相似文献
4.
Astrocytes play active roles in brain physiology. They respond to neurotransmitters and modulate neuronal excitability and synaptic function. However, the influence of astrocytes on synaptic transmission and plasticity at the single synapse level is unknown. Ca(2+) elevation in astrocytes transiently increased the probability of transmitter release at hippocampal area CA3-CA1 synapses, without affecting the amplitude of synaptic events. This form of short-term plasticity was due to the release of glutamate from astrocytes, a process that depended on Ca(2+) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein and that activated metabotropic glutamate receptors (mGluRs). The transient potentiation of transmitter release became persistent when the astrocytic signal was temporally coincident with postsynaptic depolarization. This persistent plasticity was mGluR-mediated but N-methyl-d-aspartate receptor-independent. These results indicate that astrocytes are actively involved in the transfer and storage of synaptic information. 相似文献
5.
The molecular pathways involved in retrograde signal transduction at synapses and the function of retrograde communication are poorly understood. Here, we demonstrate that postsynaptic calcium 2+ ion (Ca2+) influx through glutamate receptors and subsequent postsynaptic vesicle fusion trigger a robust induction of presynaptic miniature release after high-frequency stimulation at Drosophila neuromuscular junctions. An isoform of the synaptotagmin family, synaptotagmin 4 (Syt 4), serves as a postsynaptic Ca2+ sensor to release retrograde signals that stimulate enhanced presynaptic function through activation of the cyclic adenosine monophosphate (cAMP)-cAMP-dependent protein kinase pathway. Postsynaptic Ca2+ influx also stimulates local synaptic differentiation and growth through Syt 4-mediated retrograde signals in a synapse-specific manner. 相似文献
6.
Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission 总被引：31，自引：0，他引：31
Brief repetitive activation of excitatory synapses in the hippocampus leads to an increase in synaptic strength that lasts for many hours. This long-term potentiation (LTP) of synaptic transmission is the most compelling cellular model in the vertebrate brain for learning and memory. The critical role of postsynaptic calcium in triggering LTP has been directly examined using three types of experiment. First, nitr-5, a photolabile nitrobenzhydrol tetracarboxylate calcium chelator, which releases calcium in response to ultraviolet light, was used. Photolysis of nitr-5 injected into hippocampal CA1 pyramidal cells resulted in a large enhancement of synaptic transmission. Second, in agreement with previous results, buffering intracellular calcium at low concentrations blocked LTP. Third, depolarization of the postsynaptic membrane so that calcium entry is suppressed prevented LTP. Taken together, these results demonstrate that an increase in postsynaptic calcium is necessary to induce LTP and sufficient to potentiate synaptic transmission. 相似文献
7.
Guanosine 3',5'-monophosphate in sympathetic ganglia: increase assoicated with synaptic transmission 总被引：11，自引：0，他引：11
Brief stimulation of cholinergic preganglionic nerve fibers resulted in an increase in guanosine 3',5'-monophosphate (cyclic GMP) in the bullfrog sympathetic ganglion. When the release of synaptic transmitter was prevented by a high-magnesium, low-calcium Ringer solution, stimulation of preganglionic nerve fibers did not increase cyclic GMP in the ganglion. The increase in cyclic GMP caused by preganglionic stimulation was also blocked by the muscarinic antagonist, atropine. The data indicate that the increase in cyclic GMP is associated with synaptic transmission and support the possibility that cyclic GMP may mediate the postsynaptic action of acetylcholine at muscarinic cholinergic synapses. 相似文献
8.
Signal-processing machines at the postsynaptic density 总被引：1，自引：0，他引：1
Kennedy MB 《Science (New York, N.Y.)》2000,290(5492):750-754
Dendrites of individual neurons in the vertebrate central nervous system are contacted by thousands of synaptic terminals relaying information about the environment. The postsynaptic membrane at each synaptic terminal is the first place where information is processed as it converges on the dendrite. At the postsynaptic membrane of excitatory synapses, neurotransmitter receptors are attached to large protein "signaling machines" that delicately regulate the strength of synaptic transmission. These machines are visible in the electron microscope and are called the postsynaptic density. By changing synaptic strength in response to neural activity, the postsynaptic density contributes to information processing and the formation of memories. 相似文献
9.
SynCAM,a synaptic adhesion molecule that drives synapse assembly 总被引：1，自引：0，他引：1
Biederer T Sara Y Mozhayeva M Atasoy D Liu X Kavalali ET Südhof TC 《Science (New York, N.Y.)》2002,297(5586):1525-1531
Synapses, the junctions between nerve cells through which they communicate, are formed by the coordinated assembly and tight attachment of pre- and postsynaptic specializations. We now show that SynCAM is a brain-specific, immunoglobulin domain-containing protein that binds to intracellular PDZ-domain proteins and functions as a homophilic cell adhesion molecule at the synapse. Expression of the isolated cytoplasmic tail of SynCAM in neurons inhibited synapse assembly. Conversely, expression of full-length SynCAM in nonneuronal cells induced synapse formation by cocultured hippocampal neurons with normal release properties. Glutamatergic synaptic transmission was reconstituted in these nonneuronal cells by coexpressing glutamate receptors with SynCAM, which suggests that a single type of adhesion molecule and glutamate receptor are sufficient for a functional postsynaptic response. 相似文献
10.
The effects of pentobarbital (Nembutal) on synaptic transmission and postsynaptic potentials were studied by the use of several invertebrate preparations. Pentobarbital selectively and reversibly depressed both excitatory postsynaptic potentials and sodium-dependent postsynaptic responses to putative excitatory transmitters without affecting either inhibitory postsynaptic potentials or chloride- and potassium-dependent postsynaptic responses to putative transmitters. A selective depression of postsynaptic excitatory events was also observed with other central nervous system depressants (ethanol, chloroform, chloralose, diphenylhydantoin, and urethane). The results suggest that central and peripheral depression observed during general anesthesia is due to a selective depression of excitatory synaptic events. 相似文献
11.
Although most examples of modulation of synaptic transmission have been obtained from excitatory rather than from inhibitory connections, serotonin (5HT) is now shown to cause a presynaptic facilitation of release of the inhibitory neurotransmitter glycine. Brief local injections of this amine, or application of a 5HT uptake blocker, produce a long-lasting enhancement of both spontaneous and evoked inhibitory currents in the teleost Mauthner cell. Quantal analysis showed that the probability of release is increased. Focal recording indicated that 5HT acts directly on the inhibitory terminals, possibly reducing potassium conductances. Double staining with specific antibodies demonstrated a morphological substrate for this effect. Nerve endings that contain 5HT contact inhibitory terminals directly apposed to postsynaptic glycine receptors. 相似文献
12.
Habituation: regulation through presynaptic inhibition 总被引：1，自引：0，他引：1
During tail-flip escape responses of crayfish, synaptic transmission at the habituation-prone synapses of the lateral giant reflex pathway is presynaptically inhibited. This prevents transmitter release and all subsequent postsynaptic actions and spares the reflex from becoming habituated to stimuli produced by an animal's own escape movements. These observations demonstrate the existence of a control circuit whose adaptive function is to regulate the malleability of inherently plastic synapses. They also suggest that regulation of plasticity could be a common use of presynaptic inhibition. 相似文献
13.
Transmission between pairs of hippocampal slice neurons: quantal levels, oscillations, and LTP 总被引：3，自引：0，他引：3
R Malinow 《Science (New York, N.Y.)》1991,252(5006):722-724
Long-term potentiation (LTP) of synaptic transmission after coincident pre- and postsynaptic activity is considered a cellular model of changes underlying learning and memory. In intact tissue, LTP has been observed only between populations of neurons, making analysis of mechanisms difficult. Transmission between individual pre- and postsynaptic hippocampal cells was studied, suggesting quantal amplitude distributions with little variability in quantal size. LTP between such pairs is manifested by large, persistent, and synapse-specific potentiation with a shift in amplitude distribution that suggests presynaptic changes. Oscillations in amplitude of transmission, apparently of presynaptic origin, are common and can be triggered by LTP. 相似文献
14.
Antonova I Arancio O Trillat AC Wang HG Zablow L Udo H Kandel ER Hawkins RD 《Science (New York, N.Y.)》2001,294(5546):1547-1550
A change in the efficiency of synaptic communication between neurons is thought to underlie learning. Consistent with recent studies of such changes, we find that long-lasting potentiation of synaptic transmission between cultured hippocampal neurons is accompanied by an increase in the number of clusters of postsynaptic glutamate receptors containing the subunit GluR1. In addition, potentiation is accompanied by a rapid and long-lasting increase in the number of clusters of the presynaptic protein synaptophysin and the number of sites at which synaptophysin and GluR1 are colocalized. These results suggest that potentiation involves rapid coordinate changes in the distribution of proteins in the presynaptic neuron as well as the postsynaptic neuron. 相似文献
15.
Neurons have generally been thought to produce only one synaptic action on any particular cell which they innervate. An identified interneuron in the abdominal ganglion of Aplysia mediates both direct excitation and inhibition to an identified follower cell. At low firing rates the interneuron produces excitatory postsynaptic potentials; however at higher firing rates these gradually diminish in size and eventually invert to inhibitory postsynaptic potentials. Electrophysiological and pharmacological evidence indicates that the connection between these cells is monosynaptic, and that a single transmitter, acetylcholine, mediates both actions. These opposite synaptic responses appear to result from the transmitter's acting on two types of postsynaptic receptors having different thresholds for activation and different susceptibilities for desensitization. 相似文献
16.
Long-term potentiation (LTP) of synaptic strength, the most established cellular model of information storage in the brain, is expressed by an increase in the number of postsynaptic AMPA receptors. However, the source of AMPA receptors mobilized during LTP is unknown. We report that AMPA receptors are transported from recycling endosomes to the plasma membrane for LTP. Stimuli that triggered LTP promoted not only AMPA receptor insertion but also generalized recycling of cargo and membrane from endocytic compartments. Thus, recycling endosomes supply AMPA receptors for LTP and provide a mechanistic link between synaptic potentiation and membrane remodeling during synapse modification. 相似文献
17.
Adenosine 3',5'-monophosphate: electrophysiological evidence for a role in synaptic transmission 总被引：16，自引：0，他引：16
Synaptic potentials and changes in resting membrane potentials of superior cervical ganglia of the rabbit were measured in the presence of adenosine 3',5'-monophosphate and agents that affect its metabolism. Adenosine 3',5'-monophosphate and its mono- and dibutyryl derivatives caused a hyperpolarization of the postganglionic neurons. Theophylline potentiated the slow inhibitory postsynaptic potential that follows synaptic transmission, as well as the hyperpolarization of postganglionic neurons caused by exogenous dopamine. Conversely, prostaglandin E(1) inhibited both the slow inhibitory postsynaptic potential and the dopamine-induced hyperpolarization. We hypothesize that the slow inhibitory postsynaptic potential as well as the dopamine-induced hyperpolarization result from increased amounts of adenosine 3'5'-monophosphate in the postganglionic neurons. The dibutyryl derivative of guanosine 3'5'-monophosphate caused a depolarization of the postganglionic neurons, which is consistent with the possibility that guanosine 3'5'-monophosphate mediates synaptic transmission at muscarinic cholinergic synapses. 相似文献
18.
The normal function of neural networks depends on a delicate balance between excitatory and inhibitory synaptic inputs. Synapse formation is thought to be regulated by bidirectional signaling between pre- and postsynaptic cells. We demonstrate that members of the Neuroligin family promote postsynaptic differentiation in cultured rat hippocampal neurons. Down-regulation of neuroligin isoform expression by RNA interference results in a loss of excitatory and inhibitory synapses. Electrophysiological analysis revealed a predominant reduction of inhibitory synaptic function. Thus, neuroligins control the formation and functional balance of excitatory and inhibitory synapses in hippocampal neurons. 相似文献
19.
Newly identified 'glutamate interneurons' and their role in locomotion in the lamprey spinal cord 总被引：3，自引：0，他引：3
A new class of excitatory premotor interneurons that are important in the generation of locomotion in the lamprey has now been described. In the isolated spinal cord, these neurons act simultaneously with their postsynaptic motoneurons during fictive swimming. They are small and numerous, and they monosynaptically excite both motoneurons and inhibitory premotor interneurons. The excitatory postsynaptic potentials are depressed by an antagonist of excitatory amino acids. These interneurons receive reticulospinal input from the brain stem and polysynaptic input form skin afferents. A model of the network underlying locomotion based on the synaptic interactions of these neurons can now be proposed for the lamprey. 相似文献
20.
The dynamics of free calcium in dendritic spines in response to repetitive synaptic input 总被引：10，自引：0，他引：10
Increased levels of intracellular calcium at either pre- or postsynaptic sites are thought to precede changes in synaptic strength. Thus, to induce long-term potentiation in the hippocampus, periods of intense synaptic stimulation would have to transiently raise the levels of cytosolic calcium at postsynaptic sites--dendritic spines in the majority of cases. Since direct experimental verification of this hypothesis is not possible at present, calcium levels have been studied by numerically solving the appropriate electro-diffusion equations for two different postsynaptic structures. Under the assumption that voltage-dependent calcium channels are present on dendritic spines, free intracellular calcium in spines can reach micromolar levels after as few as seven spikes in 20 milliseconds. Moreover, a short, but high-frequency, burst of presynaptic activity is more effective in raising levels of calcium and especially of the calcium-calmodulin complex than sustained low-frequency activity. This behavior is different from that seen at the soma of a typical vertebrate neuron. 相似文献