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The Journal of Neuroscience, April 18, 2007, 27(16)
This Week in The Journal
This Week in The Journal
Cellular/Molecular
The MrgD GPCR and the M-Current
Robert A. Crozier, Seena K. Ajit, Edward J. Kaftan, and Mark H. Pausch
(see pages 4492–4496)
The M-current, initially described by David Brown and Paul Adams in sympathetic ganglion neurons, regulates cell firing in many cell types. These potassium channels, composed of KCNQ2/3 heteromers, are low threshold and noninactivating, thus reducing action potential firing to sustained stimuli. As per the name, muscarine blocks M-current. This week, Crozier et al. examine the interaction of M-current in dorsal root ganglion (DRG) neurons with a member of a G-protein-coupled receptor family that is specifically expressed in sensory neurons. The Mas-related gene (Mrg) product, MrgD, is expressed only in nonpeptidergic, small-diameter nociceptors. Using the MrgD ligand ß-alanine, the authors report activation of MrgD in DRGs, leading to increased cell firing, similar to the classic effect of muscarine on the M-current. MrgD activation, and thus the blocking of M-current, appeared to involve both a pertussis toxin-sensitive pathway and activation of Gq-dependent phospholipase C.
Development/Plasticity/Repair
Sef Regulation of Auditory Brainstem Development
Victoria E. Abraira, Naomi Hyun, Andrew F. Tucker, Donald E. Coling, M. Christian Brown, Cindy Lu, Greg Hoffman, and Lisa V. Goodrich
(see pages 4273–4282)
The large family of fibroblast growth factors contributes to multiple aspects of development. Their actions are opposed by several naturally occurring antagonists, which are in themselves FGF target genes. This pattern creates feedback regulation of FGF signaling. Abraira et al. examined the effect of one of these antagonists, Sef, on cochlear development. Sef antagonizes the MAP (microtubule-associated protein) kinase pathway that is induced by FGFs. FGF15 and FGFR1 were expressed in rhombic lip, the source of progenitor cells for the cochlear nucleus complex. Sef was expressed in cells immediately adjacent to the auditory region of the rhombic lip. Overexpression of Sef in E2 chick embryos decreased the size of the auditory nucleus, whereas reduced Sef expression in mutant mice caused abnormal morphological development in some, but not all, animals. Mutant mice had normal auditory thresholds but reduced auditory brainstem responses.
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Diagrammatic view of the rhombic lip (pink) in an E12–E14 mouse embryo shows that the cochlear nucleus complex (purple) develops immediately adjacent to the rhombic lip. See the article by Abraira et al. for details.
Behavioral/Systems/Cognitive
The Ups and Downs of Cortical Activity
Pavlos Rigas and Manuel A. Castro-Alamancos
(see pages 4261–4272)
When it comes to rhythmic cortical activity, reciprocal thalamocortical connections are often involved in state-dependent cortical activity ranging from sleep to arousal to hypersynchronous activity in some types of seizures. This week, Rigas et al. examined one of the manifestations of rhythmic activity, the slow oscillation of so-called Up and Down states in cortical neurons in brain slices. The authors recorded from cells in layer IV–III of the somatosensory cortex. Up states generated in the cortex consist of 5–15 depolarizations lasting about 1 s and which cause persistent cell firing. The authors report that Up state activity drives thalamocortical relay cells. However, cutting of connections between thalamus and cortex reduced spontaneous Up states, indicating that thalamic input facilitates Up state activity. Likewise, stimulation of thalamus triggered cortical Up states, whereas local cortical stimulation reduced Up states.
Neurobiology of Disease
AD Mice Turn to Fish Oil
Kim N. Green, Hilda Martinez-Coria, Hasan Khashwji, Eileen B. Hall, Karin A. Yurko-Mauro, Lorie Ellis, and Frank M. LaFerla
(see pages 4385–4395)
Fish oil may not be a major component of the diet of the average mouse, but it is good for Alzheimer disease mice, according to a report from Green et al. this week. The authors supplemented mouse chow with docosahexaenoic acid (DHA), an omega n-3 polyunsaturated fatty acid found in fish, and which is a major component of neuronal cell membranes. 3xTg-AD mice that exhibit Aß and tau pathology showed decreases in soluble Aß as well as reductions in tau levels after 3 months of diet supplementation. Reductions of Aß and tau were less striking after 6 and 9 months of supplementation when the diet also contained n-6 fatty acids. The n-6 fatty acids did appear to affect phosphorylation of tau. The authors looked at a number of the steps that could be responsible for the reduction in Aß and tau and found that DHA supplementation reduced presenilin 1, a component of the
-secretase complex.
Related articles in J. Neurosci.:
- Thalamocortical Up States: Differential Effects of Intrinsic and Extrinsic Cortical Inputs on Persistent Activity
- Pavlos Rigas and Manuel A. Castro-Alamancos
J. Neurosci. 2007 27: 4261-4272.[Abstract] [Full Text] - Changes in Sef Levels Influence Auditory Brainstem Development and Function
- Victoria E. Abraira, Naomi Hyun, Andrew F. Tucker, Donald E. Coling, M. Christian Brown, Cindy Lu, Gregory R. Hoffman, and Lisa V. Goodrich
J. Neurosci. 2007 27: 4273-4282.[Abstract] [Full Text] - Dietary Docosahexaenoic Acid and Docosapentaenoic Acid Ameliorate Amyloid-ß and Tau Pathology via a Mechanism Involving Presenilin 1 Levels
- Kim N. Green, Hilda Martinez-Coria, Hasan Khashwji, Eileen B. Hall, Karin A. Yurko-Mauro, Lorie Ellis, and Frank M. LaFerla
J. Neurosci. 2007 27: 4385-4395.[Abstract] [Full Text] - MrgD Activation Inhibits KCNQ/M-Currents and Contributes to Enhanced Neuronal Excitability
- Robert A. Crozier, Seena K. Ajit, Edward J. Kaftan, and Mark H. Pausch
J. Neurosci. 2007 27: 4492-4496.[Abstract] [Full Text]
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