Cellular/Molecular
Dynamic Axonal Properties Alter Spike Shape and Speed
Aleksander W. Ballo and Dirk Bucher
(see pages 5062–5074)
As action potentials propagate along an axon from the spike initiation zone to the presynaptic terminals, their shape and speed can be altered by changes in the state of various voltage-gated ion channels. These changes can impact synaptic transmission: broadening of the action potential can increase calcium influx at the terminal, thereby increasing transmitter release and postsynaptic EPSCs; and changes in conduction speed can change the pattern of presynaptic activity and thus affect spike-timing-dependent coding and plasticity. Ballo and Bucher found that changes in shape and conduction speed occur in propagating action potentials in a lobster stomatogastric neuron that fires in rhythmic bursts. Variations in spike frequency during and between bursts affected interspike and interburst membrane potential and spike amplitude and duration. These changes were likely mediated in part by activation and inactivation of voltage-gated sodium channels, as well as the counterbalancing actions of a hyperpolarization-activated inward current and a slow afterhyperpolarization.
Spikes in a single burst in a lobster neuron have different conduction delays. Each trace shows an extracellular recording aligned to a different intracellularly recorded spike, with the extracellular spike corresponding to each intracellular one shown in black. See the article by Ballo and Bucher for details.
Development/Plasticity/Repair
Stem Cells' Ability to Differentiate Might Be Limited
Fang Liu, Yan You, Xiaosu Li, Tong Ma, Yanzhen Nie, Bin Wei, Tiejun Li, Huanbing Lin, and Zhengang Yang
(see pages 5075–5087)
The realization that new neurons are born throughout an animal's life has sustained hopes that adult neurogenesis can be harnessed to repair damaged brains. Additional promise was seen in the discovery of increased neurogenesis in the subventricular zone (SVZ) after stroke, and infiltration of some of these SVZ-derived neuroblasts into the striatum. Contrary to earlier findings, however, Liu et al. now report that the ability of these neuroblasts to differentiate and replace many of the neuronal types destroyed by injury may be extremely limited. In fact, the authors did not find any newborn neurons that expressed proteins characteristic of medium spiny neurons—the primary output neurons of the striatum—after stroke. Instead, nearly all newly generated neurons expressed markers that were more characteristic of interneurons of the olfactory bulb, the main target of SVZ-derived neuroblasts in the uninjured brain. Such interneurons were rarely found in the undamaged striatum.
Behavioral/Systems/Cognitive
Two Forms of PKC Underlie Synaptic Facilitation
Greg Villareal, Quan Li, Diancai Cai, Ann E. Fink, Travis Lim, Joanna Bougie, Wayne S. Sossin, and David L. Glanzman
(see pages 5100–5107)
The sensorimotor synapse responsible for the siphon withdrawal reflex in Aplysia has proven valuable for identifying many molecules that underlie synaptic plasticity, and it is continuing to offer new discoveries. Pure motor neuron cultures have been used to identify the postsynaptic molecules that mediate serotonin-induced intermediate-term (1–3 h) facilitation (ITF) of glutamate-evoked potentials. Previous studies showed that induction of ITF requires calcium influx, vesicle exocytosis, and trafficking of AMPA receptors. Villareal et al. now present evidence that different forms of protein kinase C (PKC) are important for the induction and maintenance of ITF. Phorbol esters, which stimulate conventional diacylglycerol-dependent PKCs mimicked the effects of serotonin, facilitating glutamate potentials. Inhibiting these forms of PKC blocked induction but not maintenance of ITF. In contrast, maintenance was blocked by an inhibitor that blocks PKM, a protease cleavage product of an atypical, diacylglycerol-independent PKC. The authors conclude that both conventional and atypical PKCs are required for ITF.
Neurobiology of Disease
Astrocytes Might Contribute to Rett Syndrome
Izumi Maezawa, Susan Swanberg, Danielle Harvey, Janine M. LaSalle, and Lee-Way Jin
(see pages 5051–5061)
Rett syndrome is an X-linked neurodevelopmental disorder characterized by motor and cognitive impairments that appear in children after 6–18 months of normal development. It is caused by mutations in the transcriptional repressor methyl-CpG-binding protein-2 (MeCP2). Symptoms of Rett syndrome are generally thought to arise from loss of MeCP2 in neurons, in part because previous studies did not detect MeCP2 in glia. Maesawa et al. now report that MeCP2 is in fact expressed in astrocytes in mice. Compared to wild-type astrocytes, those expressing mutated MeCP2 had slower growth, altered expression of growth factors and interleukins, and decreased ability to promote dendritic outgrowth from cocultured wild-type neurons. Interestingly, when mutant and wild-type astrocytes were cocultured, MeCP2 expression in the latter decreased over time. Gap junction blockers prevented this spread, suggesting that an inhibitory factor passes through gap junctions and spreads MeCP deficiency throughout the population. This slowly spreading impairment might explain the delayed onset of symptoms in heterozygotes.
