The Journal of Neuroscience, November 24, 2004 • 24(47):i • i This Week in The Journal

F Cellular/Molecular courtship training paradigm in which ࡗ Neurobiology of Disease male flies court mated females and phero- Lighting Up FMRP Protein monal cues from the females suppress Neural Progenitor Cell Transplants Expression courtship. In subsequent trials with virgin in Niemann–Pick Mice females, the trained male flies also show Lisa A. Gabel, Sandra Won, Hideki suppressed courtship. Apparently, for L. S. Shihabuddin, S. Numan, M. R. Kawai, Margaret McKinney, Alan M. flies at least, rejection is a powerful learn- Huff, J. C. Dodge, J. Clarke, S. L. Tartakoff, and Justin R. Fallon ing experience. The authors manipulated Macauley, W. Yang, T. V. Taksir, G. (see pages 10579–10583) the expression of two forms of CaMKII: a Parsons, M. A. Passini, F. H. Gage, and calcium-independent and constitutively The most common form of inherited G. R. Stewart active form (T287D) or a strictly calcium- mental retardation, Fragile X syndrome (see pages 10642–10651) dependent form (T287A). After training, (FXS), results from triplet repeat expan- wild-type flies displayed a lag before sup- Without acid sphingomyelinase (ASM), sion in the Fmr1 gene, leading to loss of pression of courtship behavior that was lysosomes accumulate excess sphingomy- Fragile X mental retardation protein absent in T287D-expressing flies. The re- elin and cholesterol, resulting in the in- (FMRP) expression. Normally, FMRP sults suggest a threshold requirement for herited type-A Niemann–Pick disease binds to and represses translation of calcium-independent CaMKII in this (NPD-A), a fatal childhood disorder with mRNAs, including those expressed in learned behavior, specifically in antennal enlarged organs and neurodegeneration. dendrites and near synapses. Adding to lobe and mushroom body neurons. Various therapeutic approaches have the idea that FMRP is important for syn- been tried in such storage diseases, and aptic plasticity, mice lacking FMRP show f Behavioral/Systems/Cognitive now neural progenitor cells (NPCs) are deficient cortical long-term potentiation, Neurogranin and Synaptic Plasticity taking center stage. This week Shihabud- enhanced hippocampal long-term de- din et al. isolated NPCs from adult mouse pression, and abnormal dendritic spines. Kuo-Ping Huang, Freesia L. Huang, forebrain and transduced them with a ret- In this issue, Gabel et al. report that FMRP Tino Ja¨ger, Junfa Li, Klaus G. Reymann, roviral vector driving overexpression of expression is dynamically regulated in and Detlef Balschun human ASM (hASM). Once transplanted vivo in dark-reared, light-exposed rats. In (see pages 10660–10669) into the brains of mice lacking the ASM visual cortical neurons, FMRP expression gene, the engineered cells migrated away increased after only 15 min of visual expe- Location is everything in calcium signal- from the injection site, differentiated into rience and quickly returned to baseline. ing. Thus proteins that bind calcium, or neurons, and survived for up to 10 weeks. Blocking NMDA receptors prevented the calcium-binding proteins, are potential In vitro, ASM activity released from gene- upregulation. The protein localized to cell regulators of neuronal signaling. Neuro- modified NPCs was fivefold higher than bodies, dendrites, and synaptic fractions, granin (Ng), a 78 aa peptide, is interesting controls. Although immunostaining de- consistent with a role in synaptic plastic- in this regard. It binds calmodulin and, tected only low levels of hASM in vivo, ity. Interestingly, the regulation was post- when phosphorylated, it enhances mobi- PCR showed expression of ASM mRNA, transcriptional, because FMRP mRNA lization of calcium from internal stores. and, most importantly, pathological accu- levels remained constant, suggesting that When bound to Ng, calmodulin is less apt mulation of cholesterol was reduced, at the increased levels might be attributable to complex with calcium or calcium/ least in the region to which the NPCs mi- to altered degradation of FMRP. calmodulin-dependent protein kinase II. grated. It’s encouraging, but hurdles re- Œ Phosphorylation by protein kinase C also main before this can become a treatment Development/Plasticity/Repair reduces Ng binding to calmodulin. This strategy for this disorder. Teasing Apart CaMKII-Dependent week, Huang et al. compared mice with two copies, one copy, or no copies of the Behavior Ng gene. Knock-out mice displayed im- Jennifer E. Mehren and Leslie C. paired spatial learning (in a Morris water Griffith maze task), reduced long-term potentia- (see pages 10584–10593) tion, and small calcium transients in CA1 pyramidal cells. The authors conclude The conversion of calcium/calmodulin- that Ng normally buffers calmodulin, dependent protein kinase II (CaMKII) thereby increasing free intracellular cal- from inactive to active by autophosphor- cium and boosting calcium-dependent ylation is much discussed as a molecular synaptic potentiation. Wild-type hip- A, Transduced neuronal precursor cells express hASM (red) 1 switch in synaptic plasticity. This week pocampal neurons and dendrites ex- week after selection. B, High magnification shows punctate Mehren and Griffith compared the roles pressed Ng at a much higher concentra- lysosomal localization of hASM. Nuclei are counterstained of calcium-dependent and -independent tion than calmodulin, supporting such a bluewith4Ј,6Ј-diamidino-2-phenylindole.Seethearticleby forms of CaMKII in flies. They used a “mass-action” mechanism. Shihabuddin et al. for details.