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Chicken ovalbumin upstream promotor–transcription factor I (COUP-TFI), an orphan member of the nuclear receptor superfamily, is highly expressed in the developing nervous systems. In the cerebral cortex of Coup-tfI mutants, cortical layer IV was absent due to excessive cell death, a consequence of the failure of thalamocortical projections. Moreover, subplate neurons underwent improper differentiation...
We used functional magnetic resonance imaging (fMRI) to investigate brain regions involved in extracting three-dimensional structure from motion. A factorial design included two-dimensional and three-dimensional structures undergoing rigid and nonrigid motions. As predicted from monkey data, the human homolog of MT/V5 was significantly more active when subjects viewed three-dimensional (as opposed...
G protein–coupled receptor kinase 5 (GRK5) is a member of a family of enzymes that phosphorylate activated G protein–coupled receptors (GPCR). To address the physiological importance of GRK5-mediated regulation of GPCRs, mice bearing targeted deletion of the GRK5 gene (GRK5-KO) were generated. GRK5-KO mice exhibited mild spontaneous hypothermia as well as pronounced behavioral supersensitivity upon...
Bone morphogenetic proteins (BMPs) induce autonomic neurogenesis in neural crest cultures and stimulate sympathetic neuron development when overexpressed in vivo. We demonstrate that inhibition of BMPs in the chick embryo by the BMP antagonist Noggin prevents sympathetic neuron generation. In Noggin-treated embryos, the noradrenergic marker genes tyrosine hydroxylase (TH) and dopamine-β-hydroxylase...
SV2 proteins are abundant synaptic vesicle proteins expressed in two major (SV2A and SV2B) and one minor isoform (SV2C) that resemble transporter proteins. We now show that SV2B knockout mice are phenotypically normal while SV2A- and SV2A/SV2B double knockout mice exhibit severe seizures and die postnatally. In electrophysiological recordings from cultured hippocampal neurons, SV2A- or SV2B-deficient...
Orexin (hypocretin) appears to play a role in the regulation of energy balances. Previous reports have indicated that orexin-containing neurons are found only in the lateral hypothalamic (LH) area. We show that a subset of neurons in the gut which also express leptin receptors display orexin-like immunoreactivity and express functional orexin receptors. Orexin excites secretomotor neurons in the guinea...
Physiological, computational, and psychophysical studies of stereopsis have assumed that the perceived surface structure of binocularly viewed images is primarily specified by the pattern of binocular disparities in the two eyes' views. A novel set of stereoscopic phenomena are reported that demonstrate the insufficiency of this view. It is shown that the visual system computes the contrast relationships...
Endogenous high-affinity Ca2+ buffering and its roles were investigated in mouse cerebellar Purkinje cells with the use of a low-affinity Ca2+ indicator and a high-affinity caged Ca2+ compound. Increases in the cytosolic Ca2+ concentration ([Ca2+]i) were markedly facilitated during repetitive depolarization, resulting in the generation of steep micromolar Ca2+ gradients along dendrites. Such supralinear...
We have evaluated the role of the Drosophila mushroom bodies (MBs) in courtship conditioning, in which experience with mated females causes males to reduce their courtship toward virgins (Siegel and Hall 1979). Whereas previous studies indicated that MB ablation abolished learning in an olfactory conditioning paradigm (deBelle and Heisenberg 1994), MB-ablated males were able to learn in the courtship...
Rapid conduction in myelinated axons depends on the generation of specialized subcellular domains to which different sets of ion channels are localized. Here, we describe the identification of Caspr2, a mammalian homolog of Drosophila Neurexin IV (Nrx-IV), and show that this neurexin-like protein and the closely related molecule Caspr/Paranodin demarcate distinct subdomains in myelinated axons. While...
Mutant ataxin-1, the expanded polyglutamine protein causing spinocerebellar ataxia type 1 (SCA1), aggregates in ubiquitin-positive nuclear inclusions (NI) that alter proteasome distribution in affected SCA1 patient neurons. Here, we observed that ataxin-1 is degraded by the ubiquitin-proteasome pathway. While ataxin-1 [2Q] and mutant ataxin-1 [92Q] are polyubiquitinated equally well in vitro, the...
The formation of the cerebellar circuitry depends on the outgrowth of connections between the two principal classes of neurons, granule neurons and Purkinje neurons. To identify genes that function in axon outgrowth, we have isolated a mouse homolog of C. elegans UNC51, which is required for axon formation, and tested its function in cerebellar granule neurons. Murine Unc51.1 encodes a novel serine/threonine...
Information processing in the nervous system depends on the creation of specific synaptic connections between neurons and targets during development. The homeodomain transcription factor Otx1 is expressed in early-generated neurons of the developing cerebral cortex. Within layer 5, Otx1 is expressed by neurons with subcortical axonal projections to the midbrain and spinal cord. Otx1 is also expressed...
Conventional imaging techniques have provided high-resolution imaging either in the spatial domain or in the temporal domain. Optical imaging utilizing voltage-sensitive dyes has long had the unrealized potential to achieve high resolution in both domains simultaneously, providing subcolumnar spatial detail with millisecond precision. Here, we present a series of developments in voltage-sensitive...
Regulation of the period (per) gene is a critical feature of circadian clock function in insects. Here, we show that per is sex-linked in the silkmoth, Antheraea pernyi. The previously described silkmoth per gene is found on the Z chromosome. Silkmoth per is not dosage compensated at either the RNA or the protein level. Although earlier studies showed the presence of an oscillating endogenous antisense...
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