Cellular/Molecular
Dendrites Contain Two Populations of CaV1.2 Channels
Valentina Di Biase, Petronel Tuluc, Marta Campiglio, Gerald J. Obermair, Martin Heine, et al.
(see pages 13682–13694)
CaV1.2 channels are the most abundant L-type voltage-sensitive calcium channels in the brain, and they contribute to NMDA-independent long-term potentiation and hippocampal-dependent spatial memory. Excessive calcium influx through CaV1.2 channels can lead to neurodegeneration. This effect is attenuated in young neurons by internalization of the channels during prolonged depolarization. This does not appear to occur in older neurons, however. Using photobleaching, pulse–chase, and single-particle tracking experiments, Di Biase et al. found that most CaV1.2 channels in mature cultures of rodent hippocampal neurons were expressed in stable clusters in dendritic shafts and spines. The turnover rate of channels in these clusters was greater than 1 h and their lateral mobility within the membrane was low. Unexpectedly, ∼20% of channels were relatively mobile, moved in and out of clusters, and were present in axons as well as dendrites. But depolarization with KCl did not change the turnover, mobility, or percentage of channels in either pool.
Development/Plasticity/Repair
FAK Is Required for BDNF-Induced Growth and Turning
Jonathan P. Myers and Timothy M. Gomez
(see pages 13585–13595)
As neurites grow, their growth cones continually extend and retract, sampling the environment for cues that promote growth and turning. Extension and retraction require continual formation and disassembly of point contacts, which involve interactions between extracellular matrix molecules, transmembrane receptors, and cytoskeletal proteins. Point contact turnover is regulated in part by focal adhesion kinase (FAK), which in turn is regulated by extracellular guidance molecules. Myers and Gomez show that brain-derived neurotrophic factor (BDNF), which promotes growth and turning of Xenopus spinal neuron neurites in vitro, requires FAK to produce these effects. BDNF increased phosphorylation of FAK, increased lamellipodium size and protrusive activity, and increased the rate of turnover of point contacts. Blocking FAK activity prevented these effects and prevented BDNF-induced acceleration of neurite growth and turning. Interestingly, BDNF-induced enlargement of lamellipodia and acceleration of point contact turnover were independently disrupted by mutating distinct phosphorylation sites on FAK, suggesting that these effects are mediated by different downstream effectors.
BDNF treatment (right) increases the area of Xenopus spinal neuron growth cones (visualized with phalloidin, red) and increases phosphorylation of the FAK target src (green). See the article by Myers and Gomez for details.
Behavioral/Systems/Cognitive
Rodents without Sweet Receptors Still Taste Polysaccharides
Yada Treesukosol, Kimberly R. Smith, and Alan C. Spector
(see pages 13527–13534)
G-protein-coupled receptors composed of T1R2 and T1R3 subunits are thought to be the only taste receptors responsive to carbohydrates in humans. These receptors are activated by mono- and disaccharides, and thus convey sweet taste. Interspecies variations in these proteins underlie differences in sweet perception. For example, cats, which lack functional T1R2 subunits, are indifferent to sweet tastes, and a variation in the extracellular portion of T1R2 makes rodents indifferent to aspartame. Unlike humans, rodents can taste polysaccharides of more than two subunits, and they prefer solutions containing starch-derived glucose polymers to water. Knocking out T1R2 or T1R3 does not eliminate the preference for glucose polymers, and Treesukosol et al. report that mice lacking both subunits continued to prefer solutions containing glucose polymers to plain water. These results indicate that rodents possess an additional carbohydrate taste receptor that is responsive to trisaccharides and longer polysaccharides, consistent with evidence that these molecules elicit a taste distinct from sweet.
Neurobiology of Disease
Homeostatic Plasticity Likely Underlies Tinnitus
Roland Schaette and David McAlpine
(see pages 13452–13457)
Tinnitus is usually associated with elevated auditory thresholds for frequencies that include that of the phantom sound. It is thought to result from plasticity in central auditory structures following peripheral damage. Although this plasticity compensates for hearing loss by amplifying input, spontaneous activity is also amplified, producing phantom sound. Some people with normal auditory thresholds experience tinnitus, however, and how central plasticity could be triggered in this population is unclear. Schaette and McAlpine recorded auditory brainstem responses of such people and found that the amplitude of auditory nerve fiber responses to loud sounds was reduced compared with controls. This suggests that high-threshold auditory fibers are selectively damaged, while the low-threshold fibers that determine auditory threshold remain largely intact. Despite reduced amplitude of afferent input, the response of subjects' midbrain auditory structures was normal, supporting the hypothesis that homeostatic plasticity increases the gain of auditory inputs when the amplitude is chronically reduced.
