This Week in The Journal

Cellular/Molecular

Calcium and Sodium Pumps Keep Mitochondria at Nodes

Chuan Li Zhang, Po Lai Ho, Douglas B. Kintner, Dandan Sun, and Shing Yan Chiu

In peripheral myelinated axons, mitochondria are concentrated at nodes of Ranvier as well as at synaptic terminals. Mitochondria accumulate in terminals because calcium that enters during neural activity inactivates a mitochondrial motor, thus preventing mitochondria from moving out of the terminal. What causes accumulation of mitochondria at nodes of Ranvier was previously unknown, but Zhang et al. report that calcium is involved there as well. Unlike at central nodes (where mitochondria are not concentrated), calcium increased locally at peripheral nodes during repetitive activity. At the same time, the velocity of nodal mitochondria decreased, pause durations increased, and the total number of moving mitochondria near nodes decreased. This effect was blocked by removing external calcium. The effect was also blocked by inhibiting the sodium pump, although this did not affect activity-dependent increases in nodal calcium. Thus, unlike at nerve terminals, sodium pumps are required in addition to calcium to concentrate mitochondria at nodes.

Development/Plasticity/Repair

Death Receptors Help Maintain Corticostriatal Connections

Jason Peter Twohig, Malcolm I. Roberts, Nuria Gavalda, Emma L. Rees-Taylor, Albert Giralt, et al.

(see pages 3782–3792)

A subset of proteins in the tumor necrosis factor receptor family have a large intracellular domain that initiates a signaling cascade leading to cell death; these are called death receptors. Death receptors are active in many pathological processes including amyotrophic lateral sclerosis, ischemia, and arthritis. But accumulating evidence suggests that death receptors also play constructive roles in development, synaptic plasticity, and neuronal survival. Death receptor 3 (DR3) is expressed constitutively in the brain, and experiments reported this week by Twohig et al. suggest that DR3 is required for maintaining corticostriatal connections throughout adulthood. Knockout of DR3, which is expressed primarily in cortical and hippocampal neurons, did not produce noticeable effects in young mice. But as the mice aged, they developed abnormal gait, hyperlocomotion, and circling behaviors. These motor defects were accompanied by increased dopamine and decreased serotonin levels in the striatum and by fewer corticostriatal projections.

Inhibiting P/Q channels (right) eliminates enhanced calcium influx in neurons expressing dominant-negative GSK-3β. See the article by Zhu et al. for details.

Behavioral/Systems/Cognitive

Subliminal Images Affect Visual Attention

Duncan E. Astle, Anna C. Nobre, and Gaia Scerif

(see pages 3567–3571)

When a subject performs a visual search task, side-to-side attention shifts are reflected in EEG recordings as a more negative dip over the posterior cortex contralateral to the attended location. This EEG component, called the N2pc, also appears when a subject recalls an item in visual short-term memory, indicating that the subject's attention is drawn to where the remembered object was originally presented. Astle et al. show that this attentional capture occurs even if the item in short-term memory is not intentionally recalled. More surprising, even subliminal visual stimuli spatially biased the attention of subjects. When two stimuli were presented subliminally, subsequent presentation of one of the stimuli produced an N2pc indicating a subject's attention was drawn to the position of the matching subliminal stimulus. As a result of this attentional capture, subjects responded more quickly on a subsequent visual discrimination task when the test object was presented where the matching subliminal stimulus had been.

Neurobiology of Disease

GSK-3 Inhibits Transmitter Release by Reducing Calcium Influx

Ling-Qiang Zhu, Dan Liu, Juan Hu, Jin Cheng, Shao-Hui Wang, et al.

(see pages 3624–3633)

Glycogen synthase kinase-3 (GSK-3) has multiple roles in neurons, including regulation of neurotransmitter release. Activation of GSK-3 reduces glutamate release, whereas GSK-3 inhibition increases release of serotonin and acetylcholine. To identify the mechanism underlying this effect, Zhu et al. overexpressed wild-type or dominant-negative GSK-3β in cultured hippocampal neurons. Overexpression reduced, whereas dominant-negative GSK-3β enhanced, depolarization-induced calcium influx and vesicle release. Inhibiting P/Q-type voltage-sensitive calcium channels eliminated the enhanced calcium influx and vesicle release in neurons expressing dominant-negative GSK-3β. In synaptosomes, activation of GSK-3β increased phosphorylation of the intracellular synaptic-protein-interaction (synprint) site of P/Q channels, and decreased interactions between P/Q channels and SNARE proteins. Thus, GSK-3β appears to regulate neurotransmission by phosphorylating the P/Q calcium channel, which not only reduces calcium influx upon depolarization, but also disrupts direct interactions between P/Q channels and synaptic membrane proteins, thus hindering formation of SNARE complexes that facilitate vesicle release.