(m,n)-Strings In IIB Matrix Model

By adding gauge fields to the D-string classical solution, which have non-zero contribution to commutators in continuum limit (extreme large $N$), we introduced $(m,n)$-strings in IIB matrix model. It is found that the size of matrices depends on the value of the electric field. The tension of these strings appears in $SL(2,Z)$ invariant form. The interaction for parallel and angled strings are found in agreement with the string theory for small electric fields.Comment: LaTeX file, 10 pages; the disccusion on weak electric field are expanded; to appear in PL

M-Branes and Their Interactions in Static Matrix Model

Different BPS M-brane configurations including single and two parallel M$p$-branes ($p$= even) and M5-branes are introduced as the classical solutions of the recently proposed Static Matrix Model. Also the long range interactions of two relatively rotated M$p$-branes (one and two angles) and M$p$-brane--anti-M$p$-brane are calculated. The results are in agreement with 11 dimensional supergravity results.Comment: Latex file, 17 pages, No Figure

The Nicotinic Acetylcholine Receptor Dα7 Is Required for an Escape Behavior inDrosophila

Acetylcholine is the major excitatory neurotransmitter in the central nervous system of insects. Mutant analysis of the Dα7 nicotinic acetylcholine receptor (nAChR) ofDrosophila shows that it is required for the giant fiber-mediated escape behavior. The Dα7 protein is enriched in the dendrites of the giant fiber, and electrophysiological analysis of the giant fiber circuit showed that sensory input to the giant fiber is disrupted, as is transmission at an identified cholinergic synapse between the peripherally synapsing interneuron and the dorsal lateral muscle motor neuron. Moreover, we found thatgfA(1), a mutation identified in a screen for giant fiber defects more than twenty years ago, is an allele ofDα7. Therefore, a combination of behavioral, electrophysiological, anatomical, and genetic data indicate an essential role for the Dα7 nAChR in giant fiber-mediated escape inDrosophila

Drosophila as a Model for MECP2 Gain of Function in Neurons

Methyl-CpG-binding protein 2 (MECP2) is a multi-functional regulator of gene expression. In humans loss of MECP2 function causes classic Rett syndrome, but gain of MECP2 function also causes mental retardation. Although mouse models provide valuable insight into Mecp2 gain and loss of function, the identification of MECP2 genetic targets and interactors remains time intensive and complicated. This study takes a step toward utilizing Drosophila as a model to identify genetic targets and cellular consequences of MECP2 gain-of function mutations in neurons, the principle cell type affected in patients with Rett-related mental retardation. We show that heterologous expression of human MECP2 in Drosophila motoneurons causes distinct defects in dendritic structure and motor behavior, as reported with MECP2 gain of function in humans and mice. Multiple lines of evidence suggest that these defects arise from specific MECP2 function. First, neurons with MECP2-induced dendrite loss show normal membrane currents. Second, dendritic phenotypes require an intact methyl-CpG-binding domain. Third, dendritic defects are amended by reducing the dose of the chromatin remodeling protein, osa, indicating that MECP2 may act via chromatin remodeling in Drosophila. MECP2-induced motoneuron dendritic defects cause specific motor behavior defects that are easy to score in genetic screening. In sum, our data show that some aspects of MECP2 function can be studied in the Drosophila model, thus expanding the repertoire of genetic reagents that can be used to unravel specific neural functions of MECP2. However, additional genes and signaling pathways identified through such approaches in Drosophila will require careful validation in the mouse model

Convergent Mechanosensory Input Structures the Firing Phase of a Steering Motor Neuron in the Blowfly, Calliphora

The first basalar muscle (B1) is 1 of 17 small steering muscles in flies that control changes in wing stroke kinematics during flight. The B1 is often tonically active, firing a single phase-locked action potential in each and every wingbeat cycle. Changes in activation phase alter the biomechanical properties of B1, which in turn cause aerodynamically relevant changes in wing motion. The phase-locked firing of the B1 motor neuron (MNB1), is thought to arise from an interaction of wingbeat-synchronous inputs from the wings and from specialized equilibrium organs called halteres that beat antiphase to the wings and function to detect angular rotation of the body during flight. We investigated how the wing and haltere inputs interact to determine the firing phase of MNB1. Our results indicate that both wing and haltere afferents make strong monosynaptic connections with MNB1, consisting of fast electrical and slow Ca^(2+)-sensitive components. Although both the wing and haltere-evoked excitatory postsynaptic potentials (EPSPs) display the two components, their relative contribution is different for the two inputs. Whereas the haltere-evoked EPSP is dominated by the fast electrical component, the wing-evoked EPSP is dominated by a large chemically mediated component and displays an additional prolonged Ca^(2+)-dependent component that is absent in the haltere-evoked EPSP. Both inputs display an activity-dependent fatigue affecting both electrical and Ca^(2+)-sensitive components, from which the haltere synapse recovers more rapidly. The net result of these synaptic differences is that the two pathways differ significantly in their relative ability to evoke action potentials in MNB1. Although the haltere pathway displays greater temporal precision, the wing pathway is stronger, judged by its ability to entrain MNB1 within a background of haltere stimulation. We propose a model by which these physiological differences play a functional role in tuning the firing phase of MNB1 during flight. The wing input may serve primarily to set the background firing phase of MNB1, whereas the haltere input serves to transiently advance the firing phase during equilibrium reflexes

Convergent Mechanosensory Input Structures the Firing Phase of a Steering Motor Neuron in the Blowfly, Calliphora

The first basalar muscle (B1) is 1 of 17 small steering muscles in flies that control changes in wing stroke kinematics during flight. The B1 is often tonically active, firing a single phase-locked action potential in each and every wingbeat cycle. Changes in activation phase alter the biomechanical properties of B1, which in turn cause aerodynamically relevant changes in wing motion. The phase-locked firing of the B1 motor neuron (MNB1), is thought to arise from an interaction of wingbeat-synchronous inputs from the wings and from specialized equilibrium organs called halteres that beat antiphase to the wings and function to detect angular rotation of the body during flight. We investigated how the wing and haltere inputs interact to determine the firing phase of MNB1. Our results indicate that both wing and haltere afferents make strong monosynaptic connections with MNB1, consisting of fast electrical and slow Ca^(2+)-sensitive components. Although both the wing and haltere-evoked excitatory postsynaptic potentials (EPSPs) display the two components, their relative contribution is different for the two inputs. Whereas the haltere-evoked EPSP is dominated by the fast electrical component, the wing-evoked EPSP is dominated by a large chemically mediated component and displays an additional prolonged Ca^(2+)-dependent component that is absent in the haltere-evoked EPSP. Both inputs display an activity-dependent fatigue affecting both electrical and Ca^(2+)-sensitive components, from which the haltere synapse recovers more rapidly. The net result of these synaptic differences is that the two pathways differ significantly in their relative ability to evoke action potentials in MNB1. Although the haltere pathway displays greater temporal precision, the wing pathway is stronger, judged by its ability to entrain MNB1 within a background of haltere stimulation. We propose a model by which these physiological differences play a functional role in tuning the firing phase of MNB1 during flight. The wing input may serve primarily to set the background firing phase of MNB1, whereas the haltere input serves to transiently advance the firing phase during equilibrium reflexes

Four Residues of the Extracellular N-Terminal Domain of the NR2A Subunit Control High-Affinity Zn2+ Binding to NMDA Receptors

12 páginas, 5 figuras, 3 tablas.NMDA receptors are allosterically inhibited by Zn2+ ions in a voltage-independent manner. The apparent affinity for Zn2+ of the heteromeric NMDA receptors is determined by the subtype of NR2 subunit expressed, with NR2A-containing receptors being the most sensitive (IC50, 20 nM) and NR2C-containing receptors being the least sensitive (IC50, 30 μM). Using chimeras constructed from these two NR2 subtypes, we show that the N-terminal LIVBP-like domain of the NR2A subunit controls the high-affinity Zn2+ inhibition. Mutations at four residues in this domain markedly reduce Zn2+ affinity (by up to >500-fold) without affecting either receptor activation by glutamate and glycine or inhibition by extracellular protons and Ni2+ ions, indicating that these residues most likely participate in high-affinity Zn2+ binding.This work was supported by grants from the European Economic Community (BMH4 CT97 2374) and from Dirreción General Enseñanza Superior y Investigación Científica (PM96–0008 to J. L.). A. F. was funded by a Chateaubriand fellowship from the French government and by the Fondation pour la Recherche Médicale.Peer reviewe

Genomic Structure and Mutational Analysis of the<i>Dα7</i> Gene

<div><p>(A) The<i>Dα7</i> gene consists of 16 exons. The 5′ and 3′UTRs are drawn in blue, and the ORF is colored red. The insertion sites of the three P-elements are shown above the gene, while the extent of each deletion generated by imprecise excision of the P-elements is depicted below.</p> <p>(B) The structural domains of the Dα7 protein are shown in a schematic representation, and the minimum extent of the lesion associated with the two deletions that remove part of the ORF are indicated by brackets, (), below. Abbreviations: LBD, ligand-binding domain; M1–M4, transmembrane domains 1–4; SP, signal peptide.</p> <p>(C) Immunostaining using an anti-Dα7 antibody is absent in<i>PΔEY6</i>. Here representative staining in the medulla is shown. The precise excision<i>PΔEY5</i> (left image) was used as a control, and whole-mount of the mutant and control brains were processed together. Scale bar, 20 μm.</p></div