| 61. |
- Kullander, Klas, et al.
(författare)
-
Kinase-dependent and kinase-independent functions of EphA4 receptors in major axon tract formation in vivo
- 2001
-
Ingår i: Neuron. - 0896-6273 .- 1097-4199. ; 29:1, s. 73-84
-
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.
|
|
| 62. |
|
|
| 63. |
- Lagerström, Malin C., et al.
(författare)
-
VGLUT2-Dependent Sensory Neurons in the TRPV1 Population Regulate Pain and Itch
- 2010
-
Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 68:3, s. 529-542
-
Tidskriftsartikel (refereegranskat)abstract
- The natural response to itch sensation is to scratch, which relieves the itch through an unknown mechanism. Interaction between pain and itch has been frequently demonstrated, and the selectivity hypothesis of itch, based on data from electrophysiological and behavioral experiments, postulates the existence of primary pain afferents capable of repressing itch. Here, we demonstrate that deletion of vesicular glutamate transporter (VGLUT) 2 in a subpopulation of neurons partly overlapping with the vanilloid receptor (TRPV1) primary afferents resulted in a dramatic increase in itch behavior accompanied by a reduced responsiveness to thermal pain. The increased itch behavior was reduced by administration of antihistaminergic drugs and by genetic deletion of the gastrin-releasing peptide receptor, demonstrating a dependence on VGLUT2 to maintain normal levels of both histaminergic and nonhistaminergic itch. This study establishes that VGLUT2 is a major player in TRPV1 thermal nociception and also serves to regulate a normal itch response.
|
|
| 64. |
- Larsson, HP, et al.
(författare)
-
A conserved glutamate is important for slow inactivation in K+ channels
- 2000
-
Ingår i: Neuron. - : Elsevier Science B.V., Amsterdam.. - 0896-6273 .- 1097-4199. ; 27:3, s. 573-583
-
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.
|
|
| 65. |
|
|
| 66. |
- Lindén, Henrik, et al.
(författare)
-
Modeling the spatial reach of the LFP
- 2011
-
Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 72:5, s. 859-872
-
Tidskriftsartikel (refereegranskat)abstract
- The local field potential (LFP) reflects activity of many neurons in the vicinity of the recording electrode and is therefore useful for studying local network dynamics. Much of the nature of the LFP is, however, still unknown. There are, for instance, contradicting reports on the spatial extent of the region generating the LFP. Here, we use a detailed biophysical modeling approach to investigate the size of the contributing region by simulating the LFP from a large number of neurons around the electrode. We find that the size of the generating region depends on the neuron morphology, the synapse distribution, and the correlation in synaptic activity. For uncorrelated activity, the LFP represents cells in a small region (within a radius of a few hundred micrometers). If the LFP contributions from different cells are correlated, the size of the generating region is determined by the spatial extent of the correlated activity.
|
|
| 67. |
- Lissek, T, et al.
(författare)
-
Building Bridges through Science
- 2017
-
Ingår i: Neuron. - : Elsevier BV. - 1097-4199 .- 0896-6273. ; 96:4, s. 730-735
-
Tidskriftsartikel (refereegranskat)
|
|
| 68. |
- Liu, Jian, et al.
(författare)
-
Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria
- 2004
-
Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 43:1, s. 5-17
-
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.
|
|
| 69. |
- Lundqvist, Mikael, et al.
(författare)
-
Gamma and Beta Bursts Underlie Working Memory
- 2016
-
Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 90:1, s. 152-164
-
Tidskriftsartikel (refereegranskat)abstract
- Working memory is thought to result from sustained neuron spiking. However, computational models suggest complex dynamics with discrete oscillatory bursts. We analyzed local field potential (LFP) and spiking from the prefrontal cortex (PFC) of monkeys performing a working memory task. There were brief bursts of narrow-band gamma oscillations (45-100 Hz), varied in time and frequency, accompanying encoding and re-activation of sensory information. They appeared at a minority of recording sites associated with spiking reflecting the to-be-remembered items. Beta oscillations (20-35 Hz) also occurred in brief, variable bursts but reflected a default state interrupted by encoding and decoding. Only activity of neurons reflecting encoding/decoding correlated with changes in gamma burst rate. Thus, gamma bursts could gate access to, and prevent sensory interference with, working memory. This supports the hypothesis that working memory is manifested by discrete oscillatory dynamics and spiking, not sustained activity.
|
|
| 70. |
|
|
