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The Journal of Neuroscience, October 25, 2006, 26(43)
This Week in The Journal
This Week in The Journal
Cellular/Molecular
Taking Flip-Flops to the Membrane
Sarah K. Coleman, Tommi Möykkynen, Chunlin Cai, Lotta von Ossowski, Esa Kuismanen, Esa R. Korpi, and Kari Keinaänen
(see pages 11220–11229)
Just when you thought you knew everything about AMPA receptor trafficking, Coleman et al. shed additional light on the steps involved in the passage of receptors from endoplasmic reticulum (ER) to the membrane. AMPA receptors are assembled from four subunit types, each of which can be alternatively spliced as either a "flip" or a "flop" version. The extracellular flip/flop region influences channel activity, as flops desensitize and deactivate more rapidly than flips. Using transfected cell lines, Coleman et al. demonstrated that the flip isoform undergoes complex glycosylation in the ER and reaches the plasma membrane at 10 times higher amounts than flop isoforms, which tends to get trapped in the ER. The flip/flop trafficking differences did not seem to depend on the same amino acids that regulate channel activity and could be rescued by coexpression with the receptor-binding protein stargazin.
Development/Plasticity/Repair
RET Signaling in Dopamine Neurons
Sanjay Jain, Judith P. Golden, David Wozniak, Elizabeth Pehek, Eugene M. Johnson Jr, and Jeffrey Milbrandt
(see pages 11230–11238)
Midbrain dopaminergic neurons get a lot of attention, and with just cause. They are the neurons lost in Parkinson's disease and also are thought to fuel reward behavior and addiction. Previous work had indicated that the glial cell-line derived neurotrophic factor (GDNF) enhances the survival of dopaminergic neurons and improves symptoms of Parkinson's disease, possibly through a RET tyrosine kinase signaling pathway. Because GDNF or RET knock-out mice die before birth, this signaling pathway has been difficult to examine. Thus, the authors created mice lacking RET expression specifically in do-paminergic neurons using the Cre-Lox system. The transgenic animals had the same striatal dopamine levels and behavioral measurements as normal controls. There was also no difference in the number, size, or appearance of dopaminergic neurons. Contrary to expectations, it appears that RET is not critical to the development, survival, or function of midbrain dopaminergic neurons...at least in normal adult mice.
Behavioral/Systems/Cognitive
Following the Rules
Eveline A. Crone, Sarah E. Donohue, Ryan Honomichl, Carter Wendelken, and Silvia A. Bunge
(see pages 11239–11247)
With age, children get better at a lot of things, including their ability to switch between tasks. This week, Crone et al. used functional magnetic resonance imaging (fMRI) to identify patterns of brain activity in volunteers, aged 8–25, cued to switch between two different tasks. Switching between tasks involves two components: rule retrieval, or the ability to learn and use prescribed rules of action to guide behavior, and task set suppression, or the ability to suppress one set of rules and access another. In adults, the ventrolateral prefrontal cortex (VLPFC) is implicated in the first component, and (pre)-supplementary motor areas (pre-SMA/SMA) in the second. The authors determined that whereas the pre-SMA/ SMA function underlying suppression processes showed the same pattern of activity in adults and adolescents, the activation pattern in the VLPFC was not yet mature in adolescents. It's food for thought for parents.
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During fMRI scanning, participants viewed a cue for 1 s; then, after a 0.5 s delay, the target stimulus was presented for 2.5 s. The left or right response was required depending on the relevant stimulus–response mapping learned before the scanning. See Crone et al. for details.
Neurobiology of Disease
The SMN Protein and Motor Axon Function
Tessa L. Carrel, Michelle L. McWhorter, Eileen Workman, Honglai Zhang, Elizabeth C. Wolstencroft, Christian Lorson, Gary Bassell, Arthur H. M. Burghes, and Christine E. Beattie
(see pages 11014–11022)
The motor neuron disease spinal muscular atrophy (SMA) results from low levels of the SMN protein. SMN is well known for its role in the biogenesis of the spliceo-somal small nuclear ribonucleoprotein (snRNP), a function required in all cell types. But what function might SMN play specifically in motor neurons? Carrel et al. sought to find out. The authors previously showed that decreasing SMN levels in zebrafish using antisense morpholinos resulted in motor axon defects. In the current study, they coinjected the morpholinos with RNAs encoding different versions of the human SMN gene. Coexpression of normal SMN RNA rescued motor axons defects, whereas RNAs carrying human SMA mutations did not. However, some mutant SMN forms retained properties necessary for snRNP biogenesis, whereas other SMN forms rescued motor axons but lacked snRNP functions. SMN, therefore, has additional, snRNP-independent functions, which are essential for motor axon outgrowth.
Related articles in J. Neurosci.:
- Survival Motor Neuron Function in Motor Axons Is Independent of Functions Required for Small Nuclear Ribonucleoprotein Biogenesis
- Tessa L. Carrel, Michelle L. McWhorter, Eileen Workman, Honglai Zhang, Elizabeth C. Wolstencroft, Christian Lorson, Gary J. Bassell, Arthur H. M. Burghes, and Christine E. Beattie
J. Neurosci. 2006 26: 11014-11022.[Abstract] [Full Text] - Isoform-Specific Early Trafficking of AMPA Receptor Flip and Flop Variants
- Sarah K. Coleman, Tommi Möykkynen, Chunlin Cai, Lotta von Ossowski, Esa Kuismanen, Esa R. Korpi, and Kari Keinänen
J. Neurosci. 2006 26: 11220-11229.[Abstract] [Full Text] - RET Is Dispensable for Maintenance of Midbrain Dopaminergic Neurons in Adult Mice
- Sanjay Jain, Judith P. Golden, David Wozniak, Elizabeth Pehek, Eugene M. Johnson, Jr, and Jeffrey Milbrandt
J. Neurosci. 2006 26: 11230-11238.[Abstract] [Full Text] - Brain Regions Mediating Flexible Rule Use during Development
- Eveline A. Crone, Sarah E. Donohue, Ryan Honomichl, Carter Wendelken, and Silvia A. Bunge
J. Neurosci. 2006 26: 11239-11247.[Abstract] [Full Text]
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