Odorant Receptors in Two Places at the Same Time
Joerg Strotmann, Olga Levai, Joerg Fleischer, Karin Schwarzenbacher, and Heinz Breer
(see pages 7754-7761)
One expected that odorant receptors would be expressed in the sensory cilia of odorant receptor neurons in the nasal epithelium, but what was odorant receptor mRNA doing in axons that project to the olfactory bulb? That surprising pattern was the first clue to the striking odorant receptor-specific targeting to glomeruli in the olfactory bulb. It also led to the suggestion that odorant receptors not only act as sensors but also participate in bulb development. Evidence for this idea has been accumulating over the past few years. This week, Strotmann et al. made peptide antibodies to the odorant receptor mOR256-17 as well as the mOR37 receptor subfamily to test for the presence of receptor protein in the olfactory bulb. Receptor immunoreactivity was present in the expected zonal pattern in the nasal epithelium and also in axon bundles approaching the olfactory bulb. Consistent with a role in axon fasciculation and/or targeting, mOR256-17 and mOR37 were expressed in axons and nerve terminals in specific sets of glomeruli.
Wnt Signaling and Dorsal Thalamic Development
Cheng-Ji Zhou, Kathleen I. Pinson, and Samuel J. Pleasure
(see pages 7632-7639)
Wnt signaling is important in the formation of the thalamus in lower vertebrates. Mammalian neural development, too, may rely on Wnt signaling through the coreceptor known as low-density lipoprotein receptor-related protein-6 (LRP6). This week, Zhou et al. examine the role of Wnt signaling on the development of the mouse diencephalon. They used an arsenal of neuronal marker molecules to assess the development of neuronal structures. Mice with a loss-of-function mutation in the LRP6 receptor failed to properly form nuclei of the dorsal thalamus and did not form projections from thalamic neurons to the cortex. The ventral thalamic structures, in contrast, for the most part formed normally. The boundary between the dorsal and ventral thalamus, the zonal limitans interthalamica, was also malformed in Wnt mutants. As in fish and flies, the Wnt/β-catenin signaling pathway appears crucial to organization of dorsal thalamic structures in mammals.
Modulating a Song with Noradrenaline
Jessica A. Cardin and Marc F. Schmidt
(see pages 7745-7753)
Norepinephrine (NE)-releasing neurons in the locus ceruleus provide arousal-associated modulation of sensory inputs throughout the brain. Cardin and Schmidt take advantage of the feedforward organization between forebrain nuclei in the zebra finch auditory system to examine such state-dependent neural processing in vivo. Arousal is known to suppress firing in the higher-order song nuclei, NIf and HVC, in response to the bird's own song (BOS). HVC neurons of lightly anesthetized birds, a state of quiescence, responded to BOS recordings, whereas awake birds did not. Injection of α-adrenergic antagonists into NIf blocked the modulation. After injection of NE into the ipsilateral NIf, neurons in the downstream target HVC, the motor control nucleus, showed a dose-dependent modulation by NE. Low doses decreased spontaneous firing but caused a net increase in response to BOS. However, high doses suppressed both spontaneous firing and BOS responses. The cellular and receptor mechanisms await further studies.
Neurobiology of Disease
sAPPα, Transthyretin, and Neuroprotection
Thor D. Stein, Nicholas J. Anders, Charles DeCarli, Sic L. Chan, Mark P. Mattson, and Jeffrey A. Johnson
(see pages 7707-7717)
The accumulation of β-amyloid (Aβ) in Alzheimer's disease (AD) is only one of the results of proteolytic cleavage of amyloid precursor protein (APP). Cleavage by β- and γ-secretase leads to Aβ production, whereas α-secretase cleavage results in a soluble form, sAPPα. This week, Stein et al. examine the apparent “neuroprotective” role of sAPPα in mice. They used mice carrying the Swedish mutation (APPSw). These mice express elevated levels of APP (and sAPPα) but do not develop AD-like neuronal degeneration. Transthyretin (TTR) and insulin-like growth factor-2 (IGF-2) are upregulated neuroprotective proteins in APPSw mice. TTR can bind Aβ and prevent Aβ fibril formation in vitro. Using antibody interference and small interfering RNA knockdown techniques, the authors demonstrate, in hippocampal slices and in vivo, that sAPPα provides the mutant mice with the protective armor of increased TTR and IGF-2 expression, thus preventing tau phosphorylation and neuronal death. Too bad that sAPPα is not at high levels in Alzheimer's patients.