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The Journal of Neuroscience, September 27, 2006, 26(39)
This Week in The Journal
This Week in The Journal
Cellular/Molecular
Proton Inactivation of Choline Transporters
Hideki Iwamoto, Randy D. Blakely, and Louis J. De Felice
(see pages 9851–9859)
Choline transporters (CHTs) are concentrated at cholinergic nerve terminals at which these sodium-coupled transport molecules deliver the goods to the cytoplasm for subsequent acetylcholine (ACh) synthesis. Iwamoto et al. examined the biophysical properties of the human CHT expressed in Xenopus laevis oocytes. Several interesting properties emerged, including constitutive leakage current in the absence of substrate and variable stoichiometry of electrogenic transport. Their results may also solve a long-standing puzzle. Because CHTs can also transport ACh at high concentrations, and the transporters are highly expressed on presynaptic vesicles, transmitter could leak from ACh-containing synaptic vesicles. However, choline transport and current were inactivated at low pH. The authors hypothesize that the acidic pH in synaptic vesicles inactivates CHTs. However, once CHT-containing vesicles fuse with the plasma membrane, the neutral extracellular pH re-activates the transporter. It seems that CHTs come with a built-in ON–OFF switch.
Development/Plasticity/Repair
MMP-2 and Wound Healing
Jung-Yu C. Hsu, Robert McKeon, Staci Goussev, Zena Werb, Jung-Uek Lee, Alpa Trivedi, and Linda J. Noble-Haeusslein
(see pages 9841–9850)
Proteolysis is not always a bad thing, according to the results of Hsu et al. In the immediate aftermath of spinal cord injury, inhibition of metalloproteinases (MMPs) can improve recovery, but only if the treatment is limited to the first few days. This pattern suggests that some MMPs have a positive effect during the later stages of wound healing and repair. The authors put the hypothesis to the test, focusing on MMP-2. Mice subjected to moderate spinal cord contusion injury expressed MMP-2 during wound healing, primarily in reactive astrocytes. This expression appeared to be beneficial, because MMP-2 null mice were impaired in locomotor function. MMP-2 null mice also developed a more extensive astrocytic scar in the injured spinal cord. Because scar formation is thought to inhibit the regeneration of injured axons, MMP-2 may act to provide a cellular environment more conducive to wound healing.
Behavioral/Systems/Cognitive
Modulation of VPM Thalamic Units by the Locus Ceruleus
David M. Devilbiss, Michelle E. Page, and Barry D. Waterhouse
(see pages 9860–9872)
The noradrenergic neurons of the locus ceruleus (LC) influence sleep and wakefulness, as well as attention and feeding, through their diffuse projections. Devilbiss et al. sought to link the established cellular actions of norepinephrine to LC function. In a technical tour de force, the authors measured the effects of LC output on the sensory response properties of single neurons in the ventral posteriomedial (VPM) thalamus of awake, quietly resting rats. Microstimulation of the LC output enhanced norepinephrine influx in VPM and modulated the responses of individual units (neurons) to whiskerpad stimulation. Although units could show cell-specific behaviors, as a group, the responsiveness of VPM neurons was facilitated at low rates of LC stimulation but showed an inverted "U" response profile as LC stimulation increased. LC stimulation also altered correlated firing between groups of VPM neurons, effectively modulating their functional connectivity.
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SH-SY5Y cells expressing the synuclein mutant A53T showed amyloidogenic aggregates (green) after differentiation for 5 d with retinoic acid. The cells were stained with an antibody against -synuclein (red; left panel and merged) and thioflavin S (green; middle panel and merged). See Mazzulli et al. for details.
Neurobiology of Disease
Cytosolic Dopamine and Synuclein Aggregation
Joseph R. Mazzulli, Amanda J. Mishizen, Benoit I. Giasson, David R. Lynch, Steven A. Thomas, Akira Nakashima, Toshiharu Nagatsu, Akira Ota, and Harry Ischiropoulos
(see pages 10068–10078)
This week, Mazzulli et al. explored the possible relationship between two events that can occur in Parkinson’s disease (PD): a decline in cellular dopamine concentrations and an increase in aggregates containing
Related articles in J. Neurosci.:
- Cytosolic Catechols Inhibit
- Joseph R. Mazzulli, Amanda J. Mishizen, Benoit I. Giasson, David R. Lynch, Steven A. Thomas, Akira Nakashima, Toshiharu Nagatsu, Akira Ota, and Harry Ischiropoulos
J. Neurosci. 2006 26: 10068-10078.[Abstract] [Full Text] - Matrix Metalloproteinase-2 Facilitates Wound Healing Events That Promote Functional Recovery after Spinal Cord Injury
- Jung-Yu C. Hsu, Robert McKeon, Staci Goussev, Zena Werb, Jung-Uek Lee, Alpa Trivedi, and Linda J. Noble-Haeusslein
J. Neurosci. 2006 26: 9841-9850.[Abstract] [Full Text] - Na+, Cl–, and pH Dependence of the Human Choline Transporter (hCHT) in Xenopus Oocytes: The Proton Inactivation Hypothesis of hCHT in Synaptic Vesicles
- Hideki Iwamoto, Randy D. Blakely, and Louis J. De Felice
J. Neurosci. 2006 26: 9851-9859.[Abstract] [Full Text] - Locus Ceruleus Regulates Sensory Encoding by Neurons and Networks in Waking Animals
- David M. Devilbiss, Michelle E. Page, and Barry D. Waterhouse
J. Neurosci. 2006 26: 9860-9872.[Abstract] [Full Text]
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