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The Journal of Neuroscience, December 17, 2003, 23(37)
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This Week in The Journal
Cellular/Molecular
Cortactin and Dendritic Spines
Activity-Dependent Redistribution and Essential Role of Cortactin in Dendritic Spine Morphogenesis
Heike Hering and Morgan Sheng
(see pages 11752-11762)
Dendritic spines remodel themselves in response to synaptic activity, one of the most visible hallmarks of synaptic plasticity. The rearrangement of these dendritic protuberances necessarily must involve cytoskeletal elements. In this issue, Hering and Sheng focus on cortactin, a protein that binds F-actin,the Arp2/3 nucleation complex, as well as scaffold proteins in the postsynaptic density. Cortactin is of particular interest, because it may facilitate the formation of new actin branches, seemingly a prerequisite for growth of new spines. The authors used short-interfering RNA (siRNA) to knock down cortactin expression in cultured hippocampal neurons. These cells formed fewer dendritic spines, whereas overexpression of cortactin led to abnormally elongated spines in pyramidal neurons, and normally aspiny inhibitory neurons also sprouted little protrusions. Activation of NMDA receptors triggered translocation of cortactin from spine heads to shafts concomitant with rearrangement of F-actin. The cortactin binding sites for F-actin and Arp2/3 were crucial for cortactin localization, whereas the authors speculate that the association with scaffold proteins may regulate spine head shape.
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Dendritic spines in cultured hippocampal neurons cotransfected with -galactosidase (red) and the spine component cortactin (green). Knockdown of cortactin with an siRNA markedly reduced dendritic spines (bottom).
Development/Plasticity/Repair
Eph-Ephrin Signaling in Moth Olfactory Sensory Axons
Interaxonal Eph-Ephrin Signaling May Mediate Sorting of Olfactory Sensory Axons in Manduca sexta
Megumi Kaneko and Alan Nighorn
(see pages 11523-11538)
The retinotopic projection map differs from the olfactory map in fundamental ways. Thus one might think that entirely different factors control their development. While the organization of retinal projections is continuous relative to their origin in the retina, the axons of olfactory receptor cells expressing the same odorant receptor converge as they enter glomeruli, although their cell bodies are scattered in the olfactory epithelium. Now a report from Kaneko and Nighorn points to the receptor tyrosine kinase Eph and its ligand ephrin, already implicated in targeting of retinal axons, as pattern guidance factors in olfactory pathways of the moth Manduca sexta. The expression of Eph-ephrin peaked during the same period in which olfactory axons reach the antennal lobe (AL), the equivalent of the mammalian olfactory bulb. Unlike the visual system, Eph-ephrin was not present in target tissue; rather, there was a remarkable complementary expression of Eph and ephrin in subsets of axons entering glomeruli. In vitro, a substratum that contained either Eph or ephrin reduced neurite outgrowth, and substratum patterned with ephrin caused neurites to-turn or stop. Thus Eph-ephrin repulsive forces between axons appear to play a role in the precise axon sorting and fasciculation that occurs in the olfactory system.
Behavioral/Systems/Cognitive
Taking Sides with fMRI
fMRI of the Conscious Rabbit during Unilateral Classical Eyeblink Conditioning Reveals Bilateral Cerebellar Activation
Michael J. Miller, Nan-kuei Chen, Limin Li, Brian Tom, Craig Weiss, John F. Disterhoft, and Alice M. Wyrwicz
(see pages 11746-11751)
Functional Asymmetry for Auditory Processing in Human Primary Auditory Cortex
Joseph T. Devlin, Josephine Raley, Elizabeth Tunbridge, Katherine Lanary, Anna Floyer-Lea, Charvy Narain, Ian Cohen, Timothy Behrens, Peter Jezzard, Paul M. Matthews, and David R. Moore
(see pages 11516-11522)
Two reports in this week's Journal use functional MRI (fMRI) to expand our view of two complex processes: associative learning and human language. In each, the pattern of brain activity was detected by the blood oxygenation level-dependent (BOLD) response. Examining the neural substrates underlying behavior has usually required invasive studies such as electrophysiology or lesioning. However fMRI provides a noninvasive alternative approach, assuming you can get the subjects to sit still. Miller et al. examined cerebellar activity during eyeblink conditioning, in which rabbits learn to blink in response to a conditioned stimulus. The fMRI revealed bilateral activation of the cerebellum that, in deep cerebellar nuclei, was refined to the ipsilateral side with training. Devlin et al. explored the brain asymmetry that underlies language, a uniquely human behavior that is predominantly a function of the left hemisphere. The authors found left hemisphere dominance at the level of the primary auditory cortex, hinting that language may have evolved from lateralized hearing. This differs strikingly from non-human primates, where the primary auditory cortex shows contralateral dominance (i.e., it is not strictly lateralized). As the authors put it, these data serve to widen the "gap" between humans and monkeys.
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