This Week in The Journal
Elongating Long-Term Potentiation
Panayiotis Tsokas, Elizabeth A. Grace, PokMan Chan, Tao Ma, Stuart C. Sealfon, Ravi Iyengar, Emmanuel M. Landau, and Robert D. Blitzer
(see pages 5833-5843)
The case for local protein synthesis in synaptic plasticity continues to grow. The first evidence came more than 20 years ago based on the presence of ribosomes in dendrites. More recent studies have demonstrated that molecules that control protein translation are in dendrites and are operative during synaptic plasticity. Among these, the mammalian target of rapamycin (mTOR) pathway drives selective translation of mRNAs for which synthesis increases translational capacity. These mRNAs, including eukaryotic elongation factor 1A (eEF1A), are characterized by terminal oligopyrimidine tracts in their 5' untranslated regions. eEF1A works by binding to aminoacyl-transfer mRNAs and transferring them to the ribosome. This week, Tsokas et al. show that mRNA for eEF1A is translated in intact or severed dendrites of rat CA1 neurons. In brain slices, high-frequency stimulation induced protein synthesis-dependent long-term potentiation (LTP) and increased eEF1A expression for up to several hours. Both LTP and eEF1A expression were blocked by mTOR inhibitors, suggesting a role for eEF1A in dendritic protein synthesis.
Neuregulin Signaling in Oligodendrocyte Maturation
Caroline R. Sussman, Timothy Vartanian, and Robert H. Miller
(see pages 5757-5762)
Oligodendrocytes require neuregulin signaling to develop into myelinating cells. For example, mice lacking neuregulin-1 have greatly reduced O4+ oligodendrocyte precursors. In this week's Journal, Sussman et al. examine the role of the neuregulin-1 receptor ErbB4 in oligodendrocyte development. The authors examined neural tube explants from mice lacking the ErbB4 receptor and from rats in which the receptor was inactivated by a blocking antibody. Unlike neuregulin-1 null mice, the absence of ErbB4 had no discernible impact on the number of O4+ oligodendrocyte progenitors. This came as a surprise, because mice lacking the neuregulin-1 receptors ErbB2 and ErbB3 also do not affect progenitors, suggesting a role for promiscuous neuregulin-1 signaling through epidermal growth factor receptor family members in early development. Maturation, however, was directly impacted by the loss of ErbB4. In ErbB4-depleted explants, mature O1+ oligodendrocytes were present in significantly greater numbers than in controls and had altered morphology. Thus neuregulin signaling both promotes and inhibits oligodendrocyte development.
Mapping Parallel Processing Pathways in Barrel Cortex
Gordon M. G. Shepherd and Karel Svoboda
(see pages 5670-5679)
Mapping cortical circuits is a painstaking business. This week, Shepherd and Svoboda use laser-scanning photostimulation to excite neurons in the rat barrel cortex and thus map their connections to layer 2/3 (L2/3) pyramidal neurons. Their efforts paid off, because they uncovered a novel ascending input onto L2/3 neurons. The L2/3 target neurons were located above the septa separating cortical barrels. Somatosensory information from the thalamus has a well established projection to layer 4 (L4) neurons in the barrel cortex; L4 neurons, in turn, project to pyramidal neurons in L2/3. The authors analyzed the relative synaptic strengths of each laminar projection onto L2/3. As expected, photostimulation of clusters of neurons in L4 excited barrel-associated L2/3 neurons. However septal-associated L2/3 neurons received their strongest input from layer 5A (L5A) neurons. The two parallel processing systems, the authors suggest, represent intracortical continuations of the subcortical lemniscal and paralemniscal systems.
Neurobiology of Disease
Tracking Green Prions in the Mouse
Sami J. Barmada and David A. Harris
(see pages 5824-5832)
The conversion of prion protein (PrP) from the wild-type form, PrPC, to the conformationally altered and pathological PrPSc remains mysterious. In this week's Journal, Barmada and Harris provide a way to track part of this process. Protein aggregation typically masks PrPSc epitopes, complicating efforts to identify their subcellular localization with antibodies. Thus the authors engineered transgenic (Tg) mice that express enhanced green fluorescent protein (EGFP)-tagged PrP under the control of the PrP promoter. They then inoculated the Tg-(PrP-EGFP) mice with scrapie prions. Although the PrP-EGFP was not converted to PrPSc, it bound to endogenously generated PrPSc. PrP-EGFP also delayed the onset of disease symptoms, indicating that it can inhibit PrPC conversion to PrPSc. Aggregates containing PrP-EGFP bound to PrPSc were found throughout the brain, particularly in the neuropil, in axons, and in the Golgi apparatus. The aggregates appeared 50 d before the onset of symptoms, thus marking some of the early stages of prion pathogenesis.