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1.
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
2.
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
3.
Large amounts of zinc are present in synaptic vesicles of mammalian central excitatory boutons and may be released during synaptic activity, but the functional significance of the metal for excitatory neurotransmission is currently unknown. Zinc (10 to 1000 micromolar) was found to have little intrinsic membrane effect on cortical neurons, but invariably produced a zinc concentration-dependent, rapid-onset, reversible, and selective attenuation of the membrane responses to N-methyl-D-aspartate, homocysteate, or quinolinate. In contrast, zinc generally potentiated the membrane responses to quisqualate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and often did not affect the response to kainate. Zinc also attenuated N-methyl-D-aspartate receptor-mediated neurotoxicity but not quisqualate or kainate neurotoxicity. The ability of zinc to specifically modulate postsynaptic neuronal responses to excitatory amino acid transmitters, reducing N-methyl-to-aspartate receptor-mediated excitation while often increasing quisqualate receptor-mediated excitation, is proposed to underlie its normal function at central excitatory synapses and furthermore could be relevant to neuronal cell loss in certain disease states. 相似文献
4.
Vasopressin and oxytocin strongly modulate autonomic fear responses, through mechanisms that are still unclear. We describe how these neuropeptides excite distinct neuronal populations in the central amygdala, which provides the major output of the amygdaloid complex to the autonomic nervous system. We identified these two neuronal populations as part of an inhibitory network, through which vasopressin and oxytocin modulate the integration of excitatory information from the basolateral amygdala and cerebral cortex in opposite manners. Through this network, the expression and endogenous activation of vasopressin and oxytocin receptors may regulate the autonomic expression of fear. 相似文献
5.
The extent to which synaptic activity can signal a sensory stimulus limits the information available to a neuron. We determined the contribution of individual synapses to sensory representation by recording excitatory postsynaptic currents (EPSCs) in cerebellar granule cells during a time-varying, quantifiable vestibular stimulus. Vestibular-sensitive synapses faithfully reported direction and velocity, rather than position or acceleration of whole-body motion, via bidirectional modulation of EPSC frequency. The lack of short-term synaptic dynamics ensured a highly linear relationship between velocity and charge transfer, and as few as 100 synapses provided resolution approaching psychophysical limits. This indicates that highly accurate stimulus representation can be achieved by small networks and even within single neurons. 相似文献
6.
Regeneration of functional synapses between individual recognizable neurons in the lamprey spinal cord 总被引：1，自引：0，他引：1
In 4- to 5-year-old sea lamprey larvae that had recovered from complete transection of the spinal cord, pairs of giant interneurons on opposite sides of the scar were impaled with microelectrodes. In 4 of 30 pairs, stimulation of the caudal cell elicited a monosynaptic electrochemical excitatory postsynaptic potential in the rostral cell. Fifty percent of such pairs were synaptically linked in control lampreys without transections. These results show regeneration of functional synaptic connections between individual neurons in a vertebrate central nervous system. 相似文献
7.
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
8.
Peptide neurotoxins from fish-hunting cone snails 总被引：39，自引：0，他引：39
B M Olivera W R Gray R Zeikus J M McIntosh J Varga J Rivier V de Santos L J Cruz 《Science (New York, N.Y.)》1985,230(4732):1338-1343
To paralyze their more agile prey, the venomous fish-hunting cone snails (Conus) have developed a potent biochemical strategy. They produce several classes of toxic peptides (conotoxins) that attack a series of successive physiological targets in the neuromuscular system of the fish. The peptides include presynaptic omega-conotoxins that prevent the voltage-activated entry of calcium into the nerve terminal and release of acetylcholine, postsynaptic alpha-conotoxins that inhibit the acetylcholine receptor, and muscle sodium channel inhibitors, the mu-conotoxins, which directly abolish muscle action potentials. These distinct peptide toxins share several common features: they are relatively small (13 to 29 amino acids), are highly cross-linked by disulfide bonds, and strongly basic. The fact that they inhibit sequential steps in neuromuscular transmission suggests that their action is synergistic rather than additive. Five new omega-conotoxins that block presynaptic calcium channels are described. They vary in their activity against different vertebrate classes, and also in their actions against different synapses from the same animal. There are susceptible forms of the target molecule in peripheral synapses of fish and amphibians, but those of mice are resistant. However, the mammalian central nervous system is clearly affected, and these toxins are thus of potential significance for investigating the presynaptic calcium channels. 相似文献
9.
Berkefeld H Sailer CA Bildl W Rohde V Thumfart JO Eble S Klugbauer N Reisinger E Bischofberger J Oliver D Knaus HG Schulte U Fakler B 《Science (New York, N.Y.)》2006,314(5799):615-620
Large-conductance calcium- and voltage-activated potassium channels (BKCa) are dually activated by membrane depolarization and elevation of cytosolic calcium ions (Ca2+). Under normal cellular conditions, BKCa channel activation requires Ca2+ concentrations that typically occur in close proximity to Ca2+ sources. We show that BKCa channels affinity-purified from rat brain are assembled into macromolecular complexes with the voltage-gated calcium channels Cav1.2 (L-type), Cav2.1 (P/Q-type), and Cav2.2 (N-type). Heterologously expressed BKCa-Cav complexes reconstitute a functional "Ca2+ nanodomain" where Ca2+ influx through the Cav channel activates BKCa in the physiological voltage range with submillisecond kinetics. Complex formation with distinct Cav channels enables BKCa-mediated membrane hyperpolarization that controls neuronal firing pattern and release of hormones and transmitters in the central nervous system. 相似文献
10.
11.
A central principle of neural integration is that excitatory and inhibitory neurotransmitters effect the opening of distinct classes of membrane ionic channels and that integration consists of the summation of the opposing ionic currents on the postsynaptic membrane. In tangential cells of crayfish optic lobes, a hyperpolarizing, biphasic synaptic potential is produced by the concurrent action of acetylcholine and gamma aminobutyric acid (GABA). Acetylcholine hyperpolarizes the cell and increases chlorine conductance. GABA depolarizes the cell by closing some of the same chloride channels. Therefore, in this case integration is achieved by the antagonistic actions of two transmitters on the same ionic channel. 相似文献
12.
At the level of individual neurons, catecholamine release increases the responsivity of cells to excitatory and inhibitory inputs. A model of catecholamine effects in a network of neural-like elements is presented, which shows that (i) changes in the responsivity of individual elements do not affect their ability to detect a signal and ignore noise but (ii) the same changes in cell responsivity in a network of such elements do improve the signal detection performance of the network as a whole. The second result is used in a computer simulation based on principles of parallel distributed processing to account for the effect of central nervous system stimulants on the signal detection performance of human subjects. 相似文献
13.
Ionizing radiation decreases veratridine-stimulated uptake of sodium in rat brain synaptosomes 总被引：1，自引：0，他引：1
Veratridine-stimulated uptake of sodium-22 in brain synaptosomes was significantly reduced by ionizing radiation over a dose range of 10 to 1000 rads. The response was dose-dependent and involved a decrease in the maximum effect of veratridine on uptake. The central nervous system may be more sensitive to ionizing radiation than generally thought, perhaps through a loss of the ability of the sodium channel to respond properly to stimulation. 相似文献
14.
朊病毒为一不含核酸的蛋白感染因子，能引起哺乳动物中枢神经组织病变，它是由正常形式的蛋白（PrPC)错误折叠成致病蛋白（PrPSc)而组成的，两种结构异型蛋白来源于同一基因，朊病毒抚养殖是通过PrPC构象转变成为PrPSc而实现的。 相似文献
15.
In invertebrate nervous systems, some long-lasting increases in synaptic efficacy result from changes in the presynaptic cell. In the vertebrate nervous system, the best understood long-lasting change in synaptic strength is long-term potentiation (LTP) in the CA1 region of the hippocampus. Here the process is initiated postsynaptically, but the site of the persistent change is unresolved. Single CA3 hippocampal pyramidal cells receive excitatory inputs from associational-commissural fibers and from the mossy fibers of dentate granule cells and both pathways exhibit LTP. Although the induction of associational-commissural LTP requires in the postsynaptic cell N-methyl-D-aspartate (NMDA) receptor activation, membrane depolarization, and a rise in calcium, mossy fiber LTP does not. Paired-pulse facilitation, which is an index of increased transmitter release, is unaltered during associational-commissural LTP but is reduced during mossy fiber LTP. Thus, both the induction and the persistent change may be presynaptic in mossy fiber LTP but not in associational-commissural LTP. 相似文献
16.
GABAA-receptor function in hippocampal cells is maintained by phosphorylation factors 总被引：10，自引：0，他引：10
Gamma aminobutyric acid (GABA) mediates fast synaptic inhibition in the central nervous system by activating the chloride-permeable GABAA channel. The GABAA conductance progressively diminishes with time when the intracellular contents of hippocampal neurons are perfused with a minimal intracellular medium. This "run down" of the GABA-activated conductance can be prevented by the inclusion of magnesium adenosine triphosphate and calcium buffer in the intracellular medium. The amount of chloride conductance that can be activated by GABA is determined by competition between a calcium-dependent process that reduces the conductance and a phosphorylation process that maintains the conductance. 相似文献
17.
Habituation: occurrence at a neuromuscular junction 总被引：1，自引：0，他引：1
At the neuromuscular junctions between the motor giant axon and fast flexor muscle fibers in crayfish, stimulation at frequencies of one per minute produces a large decline in the amplitude of excitatory junctional potentials. Recovery (dishabituation) can be brought about by increases in stimulus frequency, which trigger a potentiation process; at still higher frequencies, a second form of depression intervenes. The last process appears to be due to depletion of transmitter; the first probably depends instead upon electrical changes in presynaptic terminals. Because of the interactions between the three processes, the junctions display the properties of habituation and dishabituation usually associated with complex central nervous networks. 相似文献
18.
K D Roeder 《Science (New York, N.Y.)》1966,154(756):1515-1521
Insect-eating bats find their aerial food by sonar, through emitting ultrasonic chirps and locating sources of echoes. Certain moths have ears sensitive to these chirps and can detect bats well beyond the range of the bats' sonar. On hearing a distant bat, many moths turn and fly directly away from the source of ultrasound. Only one sense cell in each ear of a moth provides the primary nervous information for this response. This article describes my initial attempts to find out how a moth's central nervous system processes the train of chirps reaching its two ears. The ear of a restrained moth is exposed to a sequence of artifically generated ultrasonic pulses that approximates the cries made by a bat. This stimulus can be varied with respect to ultrasonic frequency (pitch), pulse intensity, pulse duration, the interval between pulses, and pulse-train duration. The more sensitive acoustic sense cell responds to all frequencies between about 15,000 and 80,000 cycles per second, but the signal that it transmits to the moth's central nervous system contains no measure of frequency within this range. However, this nerve signal reports variations in the other parameters of the stimulus. The acoustic fiber connects, in the central nervous system, with various nerve cells that transform the signal farther. The signal from a pulse-marker neuron contains no measures of pulse intensity or pulse duration, reporting only changes in interpulse interval and pulse-train duration. A train-marker neuron reports only the duration of the pulse train. The stimulus parameters may be likened to keys, each of which is necessary to gain admittance through a given door but becomes superfluous once this door has been passed. This analogy suggests one of the ways in which a signal is transformed in its passage through the nervous system, and how its specificity is assured in eliciting a given response. In addition to undergoing this kind of transformation, neural signals generated in the two directionally sensitive ears must be combined if a flying moth is to steer a course away from a distant bat. Neurons have been discovered in the central ganglia which summate signals from the right and left ears. Other neurons are inhibited in their activity by stimulation of one ear. The moth may combine signals from these neurons with motor-nerve information on the attitude of its own wings, which act as oscillating baffles modifying its directional acoustic sensitivity 20 to 40 times a second as it flaps an erratic path through the darkness. 相似文献
19.
In mammalian excitatory neurons, dendritic spines are separated from dendrites by thin necks. Diffusion across the neck limits the chemical and electrical isolation of each spine. We found that spine/dendrite diffusional coupling is heterogeneous and uncovered a class of diffusionally isolated spines. The barrier to diffusion posed by the neck and the number of diffusionally isolated spines is bidirectionally regulated by neuronal activity. Furthermore, coincident synaptic activation and postsynaptic action potentials rapidly restrict diffusion across the neck. The regulation of diffusional coupling provides a possible mechanism for determining the amplitude of postsynaptic potentials and the accumulation of plasticity-inducing molecules within the spine head. 相似文献
20.
The nucleoporins Nup58 and Nup45 are part of the central transport channel of the nuclear pore complex, which is thought to have a flexible diameter. In the crystal structure of an alpha-helical region of mammalian Nup58/45, we identified distinct tetramers, each consisting of two antiparallel hairpin dimers. The intradimeric interface is hydrophobic, whereas dimer-dimer association occurs through large hydrophilic residues. These residues are laterally displaced in various tetramer conformations, which suggests an intermolecular sliding by 11 angstroms. We propose that circumferential sliding plays a role in adjusting the diameter of the central transport channel. 相似文献