Serotonin Modulates Oscillations of the Membrane Potential in Isolated Spinal Neurons from Lampreys

Studies were performed on spinal neurons from lampreys isolated by an enzymatic/mechanical method using pronase. The effects of 100 µM serotonin (5-HT) on membrane potential oscillations induced by a variety of excitatory amino acids were studied. 5-HT was found to depolarize branched cells (presumptive motoneurons and interneurons) by 2–6 mV without inducing membrane potential oscillations. However, when oscillations were already present because of an excitatory amino acid, 5-HT changed the parameters of these oscillations, increasing the amplitudes of all types of oscillations, increasing the frequency of irregular oscillations, and increasing the duration of the depolarization plateaus accompanied by action potentials. Serotonin modulation of the effects of excitatory amino acids and the electrical activity of cells in the neural locomotor network facilitates motor activity and leads to increases in the contraction of truncal muscles and more intense movements by the animal. The possible mechanisms of receptor coactivation are discussed, along with increases in action potential frequency and changes in the parameters of the locomotor rhythm

The Effects of Serotonin on Functionally Diverse Isolated Lamprey Spinal Cord Neurons

The experiments reported here showed that application of serotonin (5-hydroxytryptamine, 5-HT) (100 µ M) did not induce any significant current through the membranes of any of the spinal neurons studied (n = 62). At the same time, the membranes of most motoneurons and interneurons (15 of 18) underwent slight depolarization (2–6 mV) in the presence of 5-HT, which was not accompanied by any change in the input resistance of the cells. Depolarization to 10–20 mV occurred in some cells (3 of 18) of these functional groups, this being accompanied by 20–60% decreases in input resistance. The same concentration of 5-HT induced transient low-amplitude depolarization of most sensory spinal neurons (dorsal sensory cells), this changing smoothly to long-term hyperpolarization by 2–7 mV. The input resistance of the cell membranes in these cases showed no significant change (n = 8). Data were obtained which provided a better understanding of the mechanism by which 5-HT modulates the activity of spinal neurons. Thus, 5-HT facilitates chemoreceptive currents induced by application of NMDA to motoneurons and interneurons, while the NMDA responses of dorsal sensory cells were decreased by 5-HT. 5-HT affected the post-spike afterresponses of neurons. 5-HT significantly decreased the amplitude of afterhyperpolarization arising at the end of the descending phase of action potentials in motoneurons and interneurons and increased the amplitude of afterdepolarization in these types of cells. In sensory spinal neurons, 5-HT had no great effect on post-spike afterresponses. The results obtained here support the suggestion that 5-HT significantly modulates the activity of spinal neurons of different functional types. 5-HT facilitates excitation induced by subthreshold depolarization in motoneurons and some interneurons, facilitating the generation of rhythmic discharges by decreasing afterhyperpolarization. In sensory cells, 5-HT enhances inhibition due to hyperpolarization, suppressing NMDA currents. The differences in the effects of 5-HT on functionally diverse neurons are presumed to be associated with the combination of different types of 5-HT receptors on the membranes of these types of spinal neurons

Uniformity of V minus Near Infrared Color Evolution of Type Ia Supernovae, and Implications for Host Galaxy Extinction Determination

From an analysis of SNe 1972E, 1980N, 1981B, 1981D, 1983R, 1998bu, 1999cl, and 1999cp we find that the intrinsic V-K colors of Type Ia SNe with multi-color light curve shape (MLCS) parameter -0.4 < Delta < +0.2 suggest a uniform color curve. V-K colors become bluer linearly with time from roughly one week before B-band maximum until one week after maximum, after which they redden linearly until four weeks after maximum. V-H colors exhibit very similar color evolution. V-J colors exhibit slightly more complex evolution, with greater scatter. The existence of V minus near infrared color relations allows the construction of near infrared light curve templates that are an improvement on those of Elias et al. (1985). We provide optical BVRI and infrared JHK photometry of the Type Ia supernovae 1999aa, 1999cl, and 1999cp. SN 1999aa is an overluminous "slow decliner" (with Delta = -0.47 mag). SN 1999cp is a moderately bright SN unreddened in its host. SN 1999cl is extremely reddened in its host. The V minus near infrared colors of SN 1999cl yield A_V = 2.01 +/- 0.11 mag. This leads to a distance for its host galaxy (M 88) in agreement with other distance measurements for members of the Virgo cluster.Comment: 57 pages, 13 postscript figures, to appear in the August 20, 2000, issue of the Astrophysical Journal. Contains updated references and a number of minor corrections dealt with when page proofs were correcte

Therapeutic complement targeting in ANCA-associated vasculitides and thrombotic microangiopathy

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of systemic autoimmune disorders characterized by necrotizing inflammation of medium-to-small vessels, a relative paucity of immune deposits, and an association with detectable circulating ANCAs. AAVs include granulomatosis with polyangiitis (renamed from Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Until recently, AAVs have not been viewed as complement-mediated disorders. However, recent findings predominantly from animal studies demonstrated a crucial role of the complement system in the pathogenesis of AAVs. Complement activation or defects in its regulation have been described in an increasing number of acquired or genetically driven forms of thrombotic microangiopathy. Coinciding with this expanding spectrum of complement-mediated diseases, the question arises as to which AAV patients might benefit from a complement-targeted therapy. Therapies directed against the complement system point to the necessity of a genetic workup of genes of complement components and regulators in patients with AAV. Genetic testing together with pluripotent stem cells and bioinformatics tools may broaden our approach to the treatment of patients with aggressive forms of AAV

Experimental Test of the Inter-Layer Pairing Models for High-Tc Superconductivity Using Grazing Incidence Infrared Reflectometry

From measurements of the far-infrared reflectivity at grazing angles of incidence with p-polarized light we determined the c-axis Josephson plasma frequencies of the single layer high T_c cuprates Tl_2Ba_2CuO_6 and La_{2-x}Sr_xCuO_4. We detected a strong plasma resonance at 50 cm^{-1} for La_{2-x}Sr_xCuO_4 in excellent agreement with previously published results. For Tl_2Ba_2CuO_6 we were able to determine an upper limit of the unscreened c-axis Josephson plasma frequency 100 cm^{-1} or a c-axis penetration depth > 15 \mu m. The small value of $\omega_J$ stands in contrast to recent a prediction based on the inter-layer tunneling mechanism of superconductivity.Comment: 4 pages, Phys. Rev. B, in press, Revtex, 4 postscript figure

Physiological and Morphological Correlates of Presynaptic Inhibition in Primary Afferents of the Lamprey Spinal Cord

Patch-clamp recordings in a whole-cell mode were performed on dorsal sensory cells enzymatically isolated from the spinal cord of two lamprey species, Ichthyomyzon unicuspis and Lampetra fluviatilis. The voltage-activated currents through calcium channels were analysed. GABA and the specific GABAB receptor agonist baclofen reduced the peak amplitude of inward Ba2+ current, as a robust alternate charge carrier through voltage-dependent Ca2+ channels. These effects were dose-dependent and reversible. GABAB receptor antagonists, 2-hydroxysaclofen and δ-amino-n-valeric acid, blocked the reduction of Ba2+ currents by GABA and baclofen, while bicuculline, a GABAA receptor antagonist, had no blocking action. GABA and baclofen did not modify the dorsal sensory cell membrane conductance, indicating that they did not activate ligand-gated channels. However, GABA, but not baclofen, considerably increased membrane conductance and induced Cl- currents in isolated multipolar neurons (presumably interneurons and/or motoneurons). These findings suggest that GABA and baclofen action on lamprey dorsal sensory cells is mediated by GABAB receptors. We concluded that GABA-mediated presynaptic inhibition of lamprey dorsal sensory cell fibers results from GABAB receptor activation followed by a decrease of inward voltage-activated calcium currents. Appositions of GABA-immunoreactive boutons to horseradish peroxidase-labeled fibers from the dorsal root were observed at the ultrastructural level in the dorsal column using postembedding immunogold cytochemistry. It seems likely that these appositions represent the morphological substrate of dorsal sensory cell fiber presynaptic inhibition. In very rare cases, ultrastructural features were observed which could be interpreted as synaptic specializations between the GABA-immunoreactive boutons and the primary afferent fibers. The extrasynaptic action of GABA as a basis of presynaptic inhibition of this population of primary afferent neurons is discussed