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Neural pathways, which couple temperature-sensing neurons to motor and autonomic outputs, allow animals to navigate away from and adjust metabolism rates in response to the temperature extremes often encountered. ttx-3 is required for the specification of the AIY interneuron in the C. elegans neural pathway that mediates thermoregulation. ttx-3 null mutant animals exhibit the same thermotactic behavioral...
The leonardo gene encodes a conserved member of the 14-3-3 protein family, which plays a role in Drosophila learning. Immunological localization of the protein shows that it is expressed at synaptic connections and enriched in presynaptic boutons of the neuromuscular junction (NMJ). Null leonardo mutants die as mature embryos. Electrophysiological assays of the mutant NMJ demonstrate that basal synaptic...
We have examined domain interactions in the rod cyclic nucleotide-gated ion channel using both physiological and biochemical interaction assays. We have found an interaction between two regions of the channel distant in primary structure, the amino-terminal region and the carboxyl-terminal region containing the cyclic nucleotide-binding (CNB) domain. The interaction in functional channels was detected...
Ranvier nodes are flanked by paranodal regions, at the level of which oligodendrocytes or Schwann cells interact closely with axons. Paranodes play a critical role in the physiological properties of myelinated nerve fibers. Paranodin, a prominent 180 kDa transmembrane neuronal glycoprotein, was purified and cloned from adult rat brain, and found to be highly concentrated in axonal membranes at their...
We have characterized the organization and expression of odorant receptor genes clustered within ∼100 kb of the zebrafish genome. Physical analysis of this genomic region reveals that the receptor genes are tightly linked in tandem arrays. The expression patterns of these genes were evaluated during development as well as in the adult olfactory epithelium. Highly related genes from this array are...
Receptor tyrosine kinases (RTKs) have long been associated with proliferation in non-neural cells, although they are also expressed in postmitotic neurons. We demonstrate that insulin-like growth factor-1 (IGF-1) induces within seconds a large, tyrosine- kinase-dependent increase in calcium channel currents in cerebellar granule neurons. Separation of channel subtypes reveals that, while P, Q, and...
The vomeronasal organ (VNO) mediates detection of pheromones related to social and reproductive behavior in most terrestrial vertebrates. We have identified a new multigene family of G protein–linked receptors (V2Rs) that are specifically expressed in the VNO. V2Rs have no significant homology to other putative pheromone receptors (V1Rs) or to olfactory receptors but are related to the Ca 2+ ...
Persistent Na + currents are thought to be important for integration of neuronal responses. Here, we show that βγ subunits of G proteins can induce persistent Na + currents. Coexpression of Gβ 2 γ 3 , Gβ 1 γ3, or Gβ 5 γ 3 , but not Gβ 1 γ 1 subunits with rat brain type IIA Na + channel α subunits in tsA-201 cells greatly...
Early cortical progenitor cells of the ventricular zone (VZ) differ from later progenitor cells of the subventricular zone (SVZ) in cell-type generation and their level of epidermal growth factor receptors (EGFRs). To determine whether differences in their behavior are causally related to EGFR number/density, we introduced extra EGFRs into VZ cells with a retrovirus in vivo and in vitro. This results...
During central nervous system (CNS) development, oligodendrocyte precursors originate in specific locations and subsequently migrate to all regions of the CNS. Here, we demonstrate that the chick optic nerve is populated by oligodendrocyte precursors, which initially appeared in a focal region at the ventral midline of the third ventricle at stage 26–27. Oligodendrocyte precursors migrated into the...
Although accurate long-distance neuronal migration is a cardinal feature of cerebral cortical development, little is known about control of this migration. The scrambler(scm) mouse shows abnormal cortical lamination that is indistinguishable from reeler. Genetic and physical mapping of scm identified yeast artificial chromosomes containing an exon of mdab1, a homolog of Drosophila disabled, which...
An early and highly specific decrease in glutathione (GSH) in the substantia nigra is associated with Parkinson's disease, and low levels of GSH lead to the degeneration of cultured dopaminergic neurons. Using immature cortical neurons and a clonal nerve cell line, it is shown that a decrease in GSH triggers the activation of neuronal 12-lipoxygenase (12-LOX), which leads to the production of peroxides,...
Frog sympathetic ganglion neurons exhibit a novel Ca 2+ uptake mechanism, release-activated calcium transport or RACT, which is manifest in both cytosolic and store [Ca 2+ ] signals as greatly accelerated Ca 2+ uptake after Ca 2+ release from internal stores. RACT is activated by Ca 2+ release but not by Ca 2+ entry and serves to selectively refill Ca...
The mechanism of neurodegeneration in CAG/polyglutamine repeat expansion diseases is unknown but is thought to occur at the protein level. Here, in studies of spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), we show that the disease protein ataxin-3 accumulates in ubiquitinated intranuclear inclusions selectively in neurons of affected brain regions. We further provide...
The significance of functional maps for cortical plasticity was investigated by imaging of intrinsic optical signals together with single-unit recording in kittens. After even a brief period of monocular deprivation during the height of the critical period, only isolated patches of visual cortex continued to respond strongly to the closed eye. These deprived-eye patches were located on the pinwheel...
In the developing mammalian retina, spontaneous waves of action potentials are present in the ganglion cell layer weeks before vision. These waves are known to be generated by a synaptically connected network of amacrine cells and retinal ganglion cells, and exhibit complex spatiotemporal patterns, characterized by shifting domains of coactivation. Here, we present a novel dynamical model consisting...
The role of cGMP in olfactory signaling is not fully understood, but it is believed to play a modulatory role in intracellular signaling in vertebrate olfactory receptor neurons (ORNs). Here, we present evidence that cGMP in ORNs may play an important role in recognition of biologically relevant odors and olfactory learning. Specifically, we investigated the cellular mechanisms underlying olfactory...
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