共查询到20条相似文献，搜索用时 31 毫秒
1.
To elucidate molecular, cellular, and circuit changes that occur in the brain during learning, we investigated the role of a glutamate receptor subtype in fear conditioning. In this form of learning, animals associate two stimuli, such as a tone and a shock. Here we report that fear conditioning drives AMPA-type glutamate receptors into the synapse of a large fraction of postsynaptic neurons in the lateral amygdala, a brain structure essential for this learning process. Furthermore, memory was reduced if AMPA receptor synaptic incorporation was blocked in as few as 10 to 20% of lateral amygdala neurons. Thus, the encoding of memories in the lateral amygdala is mediated by AMPA receptor trafficking, is widely distributed, and displays little redundancy. 相似文献
2.
Stereotyped synaptic connectivity can arise both by precise recognition between appropriate partners during synaptogenesis and by selective synapse elimination. The molecular mechanisms that underlie selective synapse removal are largely unknown. We found that stereotyped developmental elimination of synapses in the Caenorhabditis elegans hermaphrodite-specific motor neuron (HSNL) was mediated by an E3 ubiquitin ligase, a Skp1-cullin-F-box (SCF) complex composed of SKR-1 and the F-box protein SEL-10. SYG-1, a synaptic adhesion molecule, bound to SKR-1 and inhibited assembly of the SCF complex, thereby protecting nearby synapses. Thus, subcellular regulation of ubiquitin-mediated protein degradation contributes to precise synaptic connectivity through selective synapse elimination. 相似文献
3.
Control of synapse number by glia 总被引：1，自引：0，他引：1
Ullian EM Sapperstein SK Christopherson KS Barres BA 《Science (New York, N.Y.)》2001,291(5504):657-661
Although astrocytes constitute nearly half of the cells in our brain, their function is a long-standing neurobiological mystery. Here we show by quantal analyses, FM1-43 imaging, immunostaining, and electron microscopy that few synapses form in the absence of glial cells and that the few synapses that do form are functionally immature. Astrocytes increase the number of mature, functional synapses on central nervous system (CNS) neurons by sevenfold and are required for synaptic maintenance in vitro. We also show that most synapses are generated concurrently with the development of glia in vivo. These data demonstrate a previously unknown function for glia in inducing and stabilizing CNS synapses, show that CNS synapse number can be profoundly regulated by nonneuronal signals, and raise the possibility that glia may actively participate in synaptic plasticity. 相似文献
4.
El-Husseini AE Schnell E Chetkovich DM Nicoll RA Bredt DS 《Science (New York, N.Y.)》2000,290(5495):1364-1368
PSD-95 is a neuronal PDZ protein that associates with receptors and cytoskeletal elements at synapses, but whose function is uncertain. We found that overexpression of PSD-95 in hippocampal neurons can drive maturation of glutamatergic synapses. PSD-95 expression enhanced postsynaptic clustering and activity of glutamate receptors. Postsynaptic expression of PSD-95 also enhanced maturation of the presynaptic terminal. These effects required synaptic clustering of PSD-95 but did not rely on its guanylate kinase domain. PSD-95 expression also increased the number and size of dendritic spines. These results demonstrate that PSD-95 can orchestrate synaptic development and are suggestive of roles for PSD-95 in synapse stabilization and plasticity. 相似文献
5.
Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice 总被引：1，自引：0，他引：1
Clement AM Nguyen MD Roberts EA Garcia ML Boillée S Rule M McMahon AP Doucette W Siwek D Ferrante RJ Brown RH Julien JP Goldstein LS Cleveland DW 《Science (New York, N.Y.)》2003,302(5642):113-117
The most common inherited [correct] form of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting adult motor neurons, is caused by dominant mutations in the ubiquitously expressed Cu-Zn superoxide dismutase (SOD1). In chimeric mice that are mixtures of normal and SOD1 mutant-expressing cells, toxicity to motor neurons is shown to require damage from mutant SOD1 acting within nonneuronal cells. Normal motor neurons in SOD1 mutant chimeras develop aspects of ALS pathology. Most important, nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons. 相似文献
6.
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
7.
We found that, in the mouse visual cortex, action potentials generated in a single layer-2/3 pyramidal (excitatory) neuron can reliably evoke large, constant-latency inhibitory postsynaptic currents in other nearby pyramidal cells. This effect is mediated by axo-axonic ionotropic glutamate receptor-mediated excitation of the nerve terminals of inhibitory interneurons, which connect to the target pyramidal cells. Therefore, individual cortical excitatory neurons can generate inhibition independently from the somatic firing of inhibitory interneurons. 相似文献
8.
Electrical synapses are common between inhibitory neurons in the mammalian thalamus and neocortex. Synaptic modulation, which allows flexibility of communication between neurons, has been studied extensively at chemical synapses, but modulation of electrical synapses in the mammalian brain has barely been examined. We found that the activation of metabotropic glutamate receptors, via endogenous neurotransmitter or by agonist, causes long-term reduction of electrical synapse strength between the inhibitory neurons of the rat thalamic reticular nucleus. 相似文献
9.
Kamermans M Fahrenfort I Schultz K Janssen-Bienhold U Sjoerdsma T Weiler R 《Science (New York, N.Y.)》2001,292(5519):1178-1180
An essential feature of the first synapse in the retina is a negative feedback pathway from horizontal cells to cones. Here we show that at this synapse, connexin26 forms hemichannels on horizontal cell dendrites near the glutamate release site of the cones. Blocking these hemichannels hyperpolarizes horizontal cells, modulates the Ca2+ channels of the cones, and abolishes all feedback-mediated responses. We propose a feedback mechanism in which the activity of the Ca2+ channels and the subsequent glutamate release of the cones are modulated by a current through these hemichannels. Because the current through the hemichannels depends on the polarization of the horizontal cells, their activity modulates the output of the cones. 相似文献
10.
Neuron-glia adhesion is inhibited by antibodies to neural determinants 总被引：10，自引：0，他引：10
Suspensions of embryonic chick neuronal cells adhered to monolayers of glial cells, but few neurons bound to control monolayers of fibroblastic cells from meninges or skin. Neuronal cell-glial cell adhesion was inhibited by prior incubation of the neurons with Fab' fragments of antibodies to neuronal membranes. In contrast, antibodies to the neural cell adhesion molecule (N-CAM) did not inhibit the binding. These results suggest that a specific adhesive mechanism between neurons and glial cells exists and that it is mediated by CAM's that differ from those so far identified. 相似文献
11.
Glutamate has been found to play an unexpectedly important role in neuroendocrine regulation in the hypothalamus, as revealed in converging experiments with ultrastructural immunocytochemistry, optical physiology with a calcium-sensitive dye, and intracellular electrical recording. There were large amounts of glutamate in boutons making synaptic contact with neuroendocrine neurons in the arcuate, paraventricular, and supraoptic nuclei. Almost all medial hypothalamic neurons responded to glutamate and to the glutamate agonists quisqualate and kainate with a consistent increase in intracellular calcium. In all magnocellular and parvocellular neurons of the paraventricular and arcuate nuclei tested, the non-NMDA (non-N-methyl-D-aspartate) glutamate antagonist CNQX (cyano-2,3-dihydroxy-7-nitroquinoxaline) reduced electrically stimulated and spontaneous excitatory postsynaptic potentials, suggesting that the endogenous neurotransmitter is an excitatory amino acid acting primarily on non-NMDA receptors. These results indicate that glutamate plays a major, widespread role in the control of neuroendocrine neurons. 相似文献
12.
Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression 总被引：2，自引：0，他引：2
A hippocampal pyramidal neuron receives more than 10(4) excitatory glutamatergic synapses. Many of these synapses contain the molecular machinery for messenger RNA translation, suggesting that the protein complement (and thus function) of each synapse can be regulated on the basis of activity. Here, local postsynaptic protein synthesis, triggered by synaptic activation of metabotropic glutamate receptors, was found to modify synaptic transmission within minutes. 相似文献
13.
Different proteins associated with 10-nanometer filaments in cultured chick neurons and nonneuronal cells 总被引：4，自引：0，他引：4
G S Bennett S J Tapscott F A Kleinbart P B Antin H Holtzer 《Science (New York, N.Y.)》1981,212(4494):567-569
A protein of molecular size 180 kilodaltons is associated with 10-nanometer filaments in neurons and is immunologically distinct from smaller putative neurofilament subunits and from 10-nanometer filament proteins in nonneuronal cells, such as myotubes and fibroblasts. Neurons do not contain vimentin, the major filament protein in many other cells, including the nonneuronal cells in cultures of neural tissue. 相似文献
14.
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
15.
Verhage M Maia AS Plomp JJ Brussaard AB Heeroma JH Vermeer H Toonen RF Hammer RE van den Berg TK Missler M Geuze HJ Südhof TC 《Science (New York, N.Y.)》2000,287(5454):864-869
Brain function requires precisely orchestrated connectivity between neurons. Establishment of these connections is believed to require signals secreted from outgrowing axons, followed by synapse formation between selected neurons. Deletion of a single protein, Munc18-1, in mice leads to a complete loss of neurotransmitter secretion from synaptic vesicles throughout development. However, this does not prevent normal brain assembly, including formation of layered structures, fiber pathways, and morphologically defined synapses. After assembly is completed, neurons undergo apoptosis, leading to widespread neurodegeneration. Thus, synaptic connectivity does not depend on neurotransmitter secretion, but its maintenance does. Neurotransmitter secretion probably functions to validate already established synaptic connections. 相似文献
16.
Once initiated near the soma, an action potential (AP) is thought to propagate autoregeneratively and distribute uniformly over axonal arbors. We challenge this classic view by showing that APs are subject to waveform modulation while they travel down axons. Using fluorescent patch-clamp pipettes, we recorded APs from axon branches of hippocampal CA3 pyramidal neurons ex vivo. The waveforms of axonal APs increased in width in response to the local application of glutamate and an adenosine A(1) receptor antagonist to the axon shafts, but not to other unrelated axon branches. Uncaging of calcium in periaxonal astrocytes caused AP broadening through ionotropic glutamate receptor activation. The broadened APs triggered larger calcium elevations in presynaptic boutons and facilitated synaptic transmission to postsynaptic neurons. This local AP modification may enable axonal computation through the geometry of axon wiring. 相似文献
17.
We have recorded from the granular layer of the turtle cerebellum extracellular unitary potentials that appear to reflect pre- and postsynaptic events at the synapse between a single swelling of a mossy fiber and the dendritic tips of several granule cells. The presynaptic component is an all-or-none potential. It can be directly activated by spinal stimulation and is unaltered by repetitive activity or by high concentrations of magnesium. The postsynaptic component is a graded potential. It follows the presynaptic component by approximately 1 millisecond and is depressed by repetitive activity and by high concentrations of magnesium. The recording of large potentials produced by the flow of postsynaptic current within a single glomerulus suggests powerful transmission. Electron micrographs demonstrate large cerebellar glomeruli in the turtle and a substantial accumulation of mitochondria in the dendritic tips of granule cells. 相似文献
18.
Silver-intensified gold and peroxidase as dual ultrastructural immunolabels for pre- and postsynaptic neurotransmitters 总被引：3，自引：0，他引：3
A N van den Pol 《Science (New York, N.Y.)》1985,228(4697):332-335
An ultrastructural immunostaining method that uses silver-intensified gold was combined with another procedure that uses biotin peroxidase conjugates to allow simultaneous identification of two neurotransmitter-related antigens in the central nervous system. Tyrosine hydroxylase-immunoreactive neurons labeled with silver-intensified gold could be differentiated at both light and electron microscopic levels from glutamate decarboxylase-immunoreactive neurons labeled with peroxidase. Cross reactivity of the second group of immunoreagents with the first group was reduced by the heavy metal silver shell formed around the colloidal gold immunoglobulin complex. With this dual pre-embedding method, peroxidase-stained axons containing the inhibitory neurotransmitter gamma-aminobutyric acid were found to synapse directly on silver-stained dopamine neurons in the rat dorsomedial hypothalamus. This approach can be used in combination with a post-embedding immunocytochemical colloidal gold procedure, allowing ultrastructural identification of three neurotransmitter-related antigens in the same tissue section. 相似文献
19.
Lamsa KP Heeroma JH Somogyi P Rusakov DA Kullmann DM 《Science (New York, N.Y.)》2007,315(5816):1262-1266
Long-term potentiation (LTP), which approximates Hebb's postulate of associative learning, typically requires depolarization-dependent glutamate receptors of the NMDA (N-methyl-D-aspartate) subtype. However, in some neurons, LTP depends instead on calcium-permeable AMPA-type receptors. This is paradoxical because intracellular polyamines block such receptors during depolarization. We report that LTP at synapses on hippocampal interneurons mediating feedback inhibition is "anti-Hebbian":Itis induced by presynaptic activity but prevented by postsynaptic depolarization. Anti-Hebbian LTP may occur in interneurons that are silent during periods of intense pyramidal cell firing, such as sharp waves, and lead to their altered activation during theta activity. 相似文献
20.
The developmental time course of posttetanic potentiation was studied at an identified chemical synapse. In stage 11 juveniles (3 weeks after metamorphosis), the synaptic connections made by cholinergic neuron L10 onto postsynaptic neurons L2 to L6 were present but showed no posttetanic potentiation. In stage 13 adults (12 weeks after metamorphosis), the same tetanus resulted in an increase of 300 percent in the synaptic potential. A similar pattern was observed at two other identified synapses in the abdominal ganglion. Thus, the initial steps in synapse formation do not include the expression of this plastic capability. Rather, at least 10 weeks is required between the onset of synaptic function and the final expression of mature synaptic properties. 相似文献