Cellular/Molecular
Mutant Cones Do Not Kill Wild-Type Cones
Alaron Lewis, Philip Williams, Owen Lawrence, Rachel O. L. Wong, and Susan E. Brockerhoff
(see pages 382–389)
In many forms of retinal degeneration, the responsible mutation is expressed in only one photoreceptor type, but death of affected photoreceptors leads to secondary death of the unaffected type. Proposed reasons for this “bystander effect” include loss of trophic support normally supplied by the primarily affected photoreceptors, release of toxic agents by dying cells, and recruitment of other toxic mediators, such as microglia, by the dying photoreceptors. One model for studying the bystander effect is zebrafish lacking cone-specific phosphodiesterase, pde6c. In these fish, cones rapidly degenerate, and rods in the cone-rich central retina die subsequently. By transplanting wild-type cells into mutant fish embryos, however, Lewis et al. found that wild-type cones do not die in a predominantly pde6c-null retina. The results indicate that the mechanism by which dying cones trigger rod death in this model does not affect cones. Comparison of these cell types might therefore provide clues about mechanisms underlying the bystander effect.
Development/Plasticity/Repair
Boc Helps Guide Retinal Axons
Pierre J. Fabre, Tomomi Shimogori, and Frédéric Charron
(see pages 266–275)
Most retinal ganglion cell (RGC) axons cross the midline of the brain at the optic chiasm, but axons from ventrotemporal RGCs do not cross. Axons are guided at the chiasm in part by repulsive interactions between Ephrin-B2, which is expressed at the midline, and its receptor, EphB1, which is expressed on axons that do not cross the midline. Knock-out of EphB receptors does not abolish pathfinding by noncrossing axons, however, suggesting additional guidance molecules are involved. Fabre et al. demonstrate in rodents that the Sonic Hedgehog (Shh) receptor Boc contributes to repulsive guidance of ventrotemporal RGC axons. Boc was expressed in ventrotemporal RGCs, and in explants, only axons from these neurons retracted in response to Shh. Boc knock-out eliminated Shh-induced retraction in vitro and reduced the percentage of axons that did not cross the midline in vivo. In contrast, misexpression of Boc in axons that normally cross at the chiasm disrupted their pathfinding.
Time-lapse recordings show a retinal ganglion cell axon growing in culture (left). Sixty minutes after addition of Shh (right), the growth cone had collapsed and the axon had retracted. See the article by Fabre et al. for details.
Behavioral/Systems/Cognitive
Abstinence Increases Some Neuronal Responses in Nucleus Accumbens
Karine Guillem and Laura L. Peoples
(see pages 276–286)
Animals' survival depends on the ability to recognize stimuli associated with reward and to make appropriate actions to obtain the reward. The nucleus accumbens plays a central role in this process, integrating cortical and limbic inputs to produce and sustain goal-directed behaviors. But this system can have negative consequences: in drug-addicted humans, it is thought to contribute to relapse by stimulating drug seeking when stimuli associated with the drug are present. Guillem and Peoples explored the cellular mechanisms underlying these long-lasting effects by chronically recording from neurons during initial periods of nicotine self-administration and during reexposure after a period of abstinence. A subset of neurons exhibited an increase in activity when the rat self-administered nicotine. The percentage of task-activated neurons, as well as their average firing rate, increased between preabstinence and postabstinence sessions. Furthermore, the firing rate of other neurons decreased across sessions, so the difference in firing rate between task-activated and task-nonactivated neurons increased.
Neurobiology of Disease
Seizures Progressively Increase after Neonatal Hypoxic Ischemia
Shilpa D. Kadam, Andrew M. White, Kevin J. Staley, and F. Edward Dudek
(see pages 404–415)
Inadequate circulation or respiration around the time of birth can cause hypoxic-ischemic encephalopathy, which can cause cerebral palsy, mental retardation, and epilepsy. To investigate the progression of acquired epilepsy, Kadam et al. induced hypoxic ischemia in 7-d-old rats and, starting 2 or 7 months later, monitored the rats continuously with EEG and video for 5 months. Subsequent histological examination revealed that approximately half of rats had large infarcts as a result of hypoxic ischemia, whereas no neuronal death was detected in the remaining rats. In every rat that had an infarct, interictal spikes were detected by EEG on the first day of recording, and all of these rats subsequently developed recurrent spontaneous seizures. The frequency, severity, and duration of seizures increased over time, and seizures occurred in clusters separated by seizure-free periods of up to a few weeks. Rats with no apparent neuronal death never exhibited epileptiform activity or interictal spikes.
