| 1. |
- Barg, Sebastian, et al.
(författare)
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Delay between fusion pore opening and peptide release from large dense-core vesicles in neuroendocrine cells.
- 2002
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Ingår i: Neuron. - 0896-6273 .- 1097-4199. ; 33:2, s. 287-299
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Tidskriftsartikel (refereegranskat)abstract
- Peptidergic neurotransmission is slow compared to that mediated by classical neurotransmitters. We have studied exocytotic membrane fusion and cargo release by simultaneous capacitance measurements and confocal imaging of single secretory vesicles in neuroendocrine cells. Depletion of the readily releasable pool (RRP) correlated with exocytosis of 10%-20% of the docked vesicles. Some remaining vesicles became releasable after recovery of RRP. Expansion of the fusion pore, seen as an increase in luminal pH, occurred after approximately 0.3 s, and peptide release was delayed by another 1-10 s. We conclude that (1) RRP refilling involves chemical modification of vesicles already in place, (2) the release of large neuropeptides via the fusion pore is negligible and only proceeds after complete fusion, and (3) sluggish peptidergic transmission reflects the time course of vesicle emptying.
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| 2. |
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| 3. |
- Jensen, Jimmy, et al.
(författare)
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Direct activation of the ventral striatum in anticipation of aversive stimuli.
- 2003
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Ingår i: Neuron. - 0896-6273 .- 1097-4199. ; 40:6, s. 1251-1257
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Tidskriftsartikel (refereegranskat)abstract
- The brain "reward" system, centered on the limbic ventral striatum, plays a critical role in the response to pleasure and pain. The ventral striatum is activated in animal and human studies during anticipation of appetitive/pleasurable events, but its role in aversive/painful events is less clear. Here we present data from three human fMRI studies based on aversive conditioning using unpleasant cutaneous electrical stimulation and show that the ventral striatum is reliably activated. This activation is observed during anticipation and is not a consequence of relief after the aversive event. Further, the ventral striatum is activated in anticipation regardless of whether there is an opportunity to avoid the aversive stimulus or not. Our data suggest that the ventral striatum, a crucial element of the brain "reward" system, is directly activated in anticipation of aversive stimuli.
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| 4. |
- Kullander, Klas, et al.
(författare)
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Kinase-dependent and kinase-independent functions of EphA4 receptors in major axon tract formation in vivo
- 2001
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Ingår i: Neuron. - 0896-6273 .- 1097-4199. ; 29:1, s. 73-84
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Tidskriftsartikel (refereegranskat)abstract
- The EphA4 receptor tyrosine kinase regulates the formation of the corticospinal tract (CST), a pathway controlling voluntary movements, and of the anterior commissure (AC), connecting the neocortical temporal lobes. To study EphA4 kinase signaling in these processes, we generated mice expressing mutant EphA4 receptors either lacking kinase activity or with severely downregulated kinase activity. We demonstrate that EphA4 is required for CST formation as a receptor for which it requires an active kinase domain. In contrast, the formation of the AC is rescued by kinase-dead EphA4, suggesting that in this structure EphA4 acts as a ligand for which its kinase activity is not required. Unexpectedly, the cytoplasmic sterile-alpha motif (SAM) domain is not required for EphA4 functions. Our findings establish both kinase-dependent and kinase-independent functions of EphA4 in the formation of major axon tracts.
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| 5. |
- Larsson, HP, et al.
(författare)
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A conserved glutamate is important for slow inactivation in K+ channels
- 2000
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Ingår i: Neuron. - : Elsevier Science B.V., Amsterdam.. - 0896-6273 .- 1097-4199. ; 27:3, s. 573-583
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Tidskriftsartikel (refereegranskat)abstract
- Voltage-gated ion channels undergo slow inactivation during prolonged depolarizations. We investigated the role of a conserved glutamate at the extracellular end of segment 5 (S5) in slow inactivation by mutating it to a cysteine (E418C in Shaker). We could lock the channel in two different conformations by disulfide-linking 418C to two different cysteines, introduced in the Pore-S6 (P-S6) loop. Our results suggest that E418 is normally stabilizing the open conformation of the slow inactivation gate by forming hydrogen bonds with the P-S6 loop. Breaking these bonds allows the P-S6 loop to rotate, which closes the slow inactivation gate. Our results also suggest a mechanism of how the movement of the voltage sensor can induce slow inactivation by destabilizing these bonds.
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| 6. |
- Liu, Jian, et al.
(författare)
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Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria
- 2004
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 43:1, s. 5-17
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Tidskriftsartikel (refereegranskat)abstract
- One cause of amyotrophic lateral sclerosis (ALS) is mutation in ubiquitously expressed copper/zinc superoxide dismutase (SOD1), but the mechanism of toxicity to motor neurons is unknown. Multiple disease-causing mutants, but not wild-type SOD1, are now demonstrated to be recruited to mitochondria, but only in affected tissues. This is independent of the copper chaperone for SOD1 and dismutase activity. Highly preferential association with spinal cord mitochondria is seen in human ALS for a mutant SOD1 that accumulates only to trace cytoplasmic levels. Despite variable proportions that are successfully imported, nearly constant amounts of SOD1 mutants and covalently damaged adducts of them accumulate as apparent import intermediates and/or are tightly aggregated or crosslinked onto integral membrane components on the cytoplasmic face of those mitochondria. These findings implicate damage from action of spinal cord-specific factors that recruit mutant SOD1 to spinal mitochondria as the basis for their selective toxicity in ALS.
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| 7. |
- Nyberg, Lars
(författare)
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Intact frontal memory effect in older age and dementia
- 2004
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Ingår i: Neuron. - Cambridge, Mass. : Cell Press. - 0896-6273 .- 1097-4199. ; 42:5, s. 701-702
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Older adults and demented patients show preserved functioning on certain tests of implicit memory. In this issue of Neuron, Lustig and Buckner demonstrate that both groups show comparable repetition-based effects on response time and prefrontal activity relative to younger adults.
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