Articles in 2010

Przedborski and Wichterle discuss various ways in which stem cells may be used to facilitate research in neurodegeneration. Particularly, this Perspective highlights the use of induced pluripotent stem cells derived from affected individuals as a potential tool to better dissect disease mechanism of neurodegenerative diseases and to aid in restorative therapy.

Defects in the cellular homeostatic process of autophagy have been observed in various neurodegenerative disorders. In this Review, Wong and Cuervo highlight the latest literature to discuss different types of autophagic dysfunction in neurodegenerative conditions and compare the interplay between autophagy and other cellular degradation processes.

This review article highlights the recent advances on how amyloid-β (Aβ) peptides can affect synaptic and neuronal circuit function—both in the context of normal brain function and in Alzheimer's disease—and discusses the consequence of aberrant Aβ at neural network level.

The authors show that a developmental shift occurs in the dimensions of the calcium domain required for vesicle endocytosis at calyx of Held terminals. After hearing onset, endocytosis at mature synapses is largely driven by calcium nanodomains. Endocytosis becomes independent of calmodulin and calcineurin and completely dependent on GTP hydrolysis.

The authors show that a mutation in the synaptic vesicle protein otoferlin impairs hearing by reducing the rate of vesicle replenishment at the inner hair cell ribbon synapse. They propose that the function of otoferlin is to replenish synaptic vesicles.

The authors chronically stimulated cultured cortical cell networks. They observed changes in the timing of neural activity that depended on the intervals used during training.

Dieterich et al. describe a methodology to label all newly synthesized neuronal proteins in situ. This method, which they name FUNCAT, relies on the inclusion of noncanonical amino acids and selective fluorescent labeling via click chemistry. The authors show that this system is amenable to dual pulse-chase experiments and dynamic tracking of newly synthesized proteins.

The low threshold for action potential generation in the axon initial segment (AIS) is thought to reflect a high sodium channel density. Using high-speed sodium imaging, Fleidervish et al. estimate that sodium channel density in the AIS is only threefold higher than in the soma, a smaller difference than previously estimated.

Dopamine D2 receptor antagonists increase the risk of extrapyramidal symptoms (EPS) within minutes. This study reports significant reductions in the striatal volume of healthy human subjects within hours of D2R antagonist treatment; the volume changes predict structural-functional decoupling in motor circuits and acute EPS with high precision.

After neurotransmitter release evoked by intense stimulation, synaptic vesicles are retrieved either by clathrin-mediated endocytosis or by activity-dependent bulk endocytosis (ADBE), both of which require the GTPase dynamin I. Here the authors show that presynaptic glycogen synthase kinase-3 specifically regulates synaptic vesicle retrieval during ADBE via phosphorylation of dynamin I.

This study finds that inhibition of the hypothalamic melanocortin receptors increases the level of high-density lipoprotein HDL-C, a form of cholesterol, circulating in the blood stream. Uptake of HDL-C into the liver was slowed, as expression of one of the hepatic cholesterol receptors was downregulated.

The mechanisms by which the brain selects a particular stimulus as the next target for gaze are only partially understood. A cholinergic nucleus in the owl's midbrain exhibits functional properties that suggest a role for it as a 'salience map' in facilitating bottom-up stimulus selection.

To prevent false hopes and premature hype, public announcements of preliminary results from clinical trials should include access to the actual data to allow for scrutiny by experts.

A newly discovered population of glutamatergic brainstem neurons that can be activated by muscarinic agonists augments transmission from the mesencephalic locomotor region to reticulospinal neurons in the locomotor pathway.

A study in this issue finds that laboratory strains of male mice can recognize their offspring as adults if given the chance to interact with infant pups. This recognition requires prolactin-mediated adult neurogenesis in the male parent's olfactory bulb and hippocampus.

Cilia are increasingly appreciated regulators of brain homeostasis. Several recent studies examine the cellular and molecular mechanisms of their biogenesis and orientation in ependymal cells.

New work identifies a neurogenic progenitor population in the developing human and ferret cortex that may have contributed substantially to the evolution of cortical expansion and folding in higher mammals.

Combining cell group specific gene expression patterns with recent technologies has provided insights into brain circuitry. A new resource may make it possible for those studying the hypothalamus to use these techniques as well.

People vary markedly in how quickly they can resolve competitive action decisions. Using magnetic resonance spectroscopy, the authors find that the speed with which an individual resolves such competition can be predicted by the concentration of GABA in a region of frontal cortex.

Fragile X mental retardation protein (FMRP) binds to RNA and interacts with other ribonucleoproteins. Here, the authors describe both an interaction between FMRP and the sodium-activated potassium channel Slack-B and the FMRP regulation of Slack channel kinetics.