This Week in The Journal
Stereotyped Pruning of Mossy Fibers
Xiao-Bo Liu, Lawrence K. Low, Edward G. Jones, and Hwai-Jong Cheng
(see pages 9124-9134)
How axons make appropriate contacts and avoid inappropriate ones continues to occupy the lives of developmental neuroscientists. This week, Liu et al. examine the cellular mechanisms underlying the removal of long-range inappropriate axon collaterals, a process that occurs by stereotyped pruning. The authors considered three possible pruning methods: retraction, in which axonal contents are recycled; classic Wallerian degeneration; and axosome shedding, whereby axonal contents are dumped from the terminal and engulfed by glial cells. Using immunohistochemistry and electron microscopy, they examined the pruning in hippocampal mossy fibers that transiently contact the basal dendrites in layer CA3. Mossy fiber boutons contacted infrapyramidal dendrites, but these transient synaptic complexes dwindled in size and complexity as pruning progressed. There was no apparent axonal degeneration and no glial cell invasion. Thus the authors conclude that axonal retraction occurred during stereotyped pruning, a process that involves plexin-A3 signaling.
Sleep-Dependent Synaptic Plasticity
Sushil K. Jha, Brian E. Jones, Tammi Coleman, Nick Steinmetz, Chi-Tat Law, Gerald Griffin, Josh Hawk, Nooreen Dabbish, Valery Kalatsky, and Marcos G. Frank
(see pages 9266-9274)
Anyone who has tried to remember something after a sleepless night can appreciate the importance of sleep with regard to neuronal plasticity. This week, Jha et al. explore the role of sleep in ocular dominance (OD) plasticity in cats that results from monocular deprivation during the critical period. OD plasticity has long been known to depend on ongoing cortical activity and is manifest as a remodeling of synaptic weights in favor of the open eye. After 6 h of monocular deprivation, the authors reversibly silenced activity during a 6 h sleep period. As expected, EEG activity in visual cortex was suppressed after lidocaine injections into area V1. Optical imaging and microelectrode recordings in V1 showed that cats that received only a sham or vehicle injection displayed normal OD plasticity, but lidocaine-injected cats did not. Interestingly, sleep after cortical silencing did not rescue OD plasticity, revealing a critical time dependence to the effect of sleep.
BOLD, the Stress Response, and Hormonal Cycles
Jill M. Goldstein, Matthew Jerram, Russell Poldrack, Todd Ahern, David N. Kennedy, Larry J. Seidman, and Nikos Makris
(see pages 9309-9316)
In this issue, Goldstein et al. provide visual evidence of the relationship of hormones to behavior, using functional magnetic resonance imaging. Female subjects were shown a series of negative (high arousal) and neutral (low arousal) affective pictures twice during their menstrual cycle: early, when estrogen and progesterone levels are low, and midcycle, when estrogen is elevated. The authors measured electrodermal activity (EDA) to simultaneously track arousal. Blood oxygen level-dependent (BOLD) signal responses differed at the two time points in brain regions associated with the stress response: central amygdala, paraventricular and ventromedial hypothalamic nuclei, hippocampus, orbitofrontal cortex, anterior cingulate, and peripeduncular nucleus. The EDA arousal measures suggested that cortical control of the hypothalamic-pituitary-adrenal (HPA) axis decreased during the early follicular phase. The authors suggest that estrogen attenuates arousal in midcycle by cortical-subcortical control of the HPA axis. These activation patterns may help explain some sex-specific differences in behavior.
Neurobiology of Disease
CHIPing Away at polyQ Protein Aggregation
Victor M. Miller, Rick F. Nelson, Cynthia M. Gouvion, Aislinn Williams, Edgardo Rodriguez-Lebron, Scott Q. Harper, Beverly L. Davidson, Michael R. Rebagliati, and Henry L. Paulson
(see pages 9152-9161)
The C-terminal heat shock protein 70-interacting protein (CHIP) serves a potentially key triage function in protein quality control by acting as a link between molecular chaperones and the ubiquitin-proteasome degradation pathway. Poly-glutamine (polyQ) neurodegenerative diseases such as Huntington's disease (HD), with their aggregation of mutant proteins, represent failures of these quality-control systems. Thus, Miller et al. examined the modulatory effects of CHIP on polyQ protein aggregation. The authors found that wild-type CHIP coexpressed with green fluorescent protein-labeled mutant polyQ protein prevented nuclear inclusions, whereas mutant CHIP lacking its chaperone-binding tetratri-copeptide repeat domain did not. Similar results were seen with expression of the huntingtin protein Q82-Htt. CHIP suppression of polyQ aggregation appeared to depend on its cochaperone function rather than on ubiquitin ligase activity. CHIP also decreased polyQ aggregation and cell death in mouse primary neurons and in zebrafish embryos expressing polyQ proteins. Disease progression and death were accelerated in transgenic HD mice that were CHIP haploinsufficient.