Polynomial-smoothing and derivative-estimating formulas for functions of one or two independent variables

Application of polynomial-smoothing formulas and related derivative-estimating formulas simplifies certain linear least-squares problems. These problems can then be solved by a computer method

Polynomial smoothing formulas and derivative formulas for one or two independent variables

Polynomial smoothing formulas and derivative formulas for one or two independent variable

Chloride transporter KCC2-dependent neuroprotection depends on the N-terminal protein domain

Neurodegeneration is a serious issue of neurodegenerative diseases including epilepsy. Downregulation of the chloride transporter KCC2 in the epileptic tissue may not only affect regulation of the polarity of GABAergic synaptic transmission but also neuronal survival. Here, we addressed the mechanisms of KCC2-dependent neuroprotection by assessing truncated and mutated KCC2 variants in different neurotoxicity models. The results identify a threonine- and tyrosine-phosphorylation-resistant KCC2 variant with increased chloride transport activity, but they also identify the KCC2 N-terminal domain (NTD) as the relevant minimal KCC2 protein domain that is sufficient for neuroprotection. As ectopic expression of the KCC2-NTD works independently of full-length KCC2-dependent regulation of Cl(-) transport or structural KCC2 C-terminus-dependent regulation of synaptogenesis, our study may pave the way for a selective neuroprotective therapeutic strategy that will be applicable to a wide range of neurodegenerative diseases

Presynaptic mechanisms of neuronal plasticity and their role in epilepsy

Synaptic communication requires constant adjustments of pre- and postsynaptic efficacies. In addition to synaptic long term plasticity, the presynaptic machinery underlies homeostatic regulations which prevent out of range transmitter release. In this minireview we will discuss the relevance of selected presynaptic mechanisms to epilepsy including voltage- and ligand-gated ion channels as well as cannabinoid and adenosine receptor signaling

Electrophysiological signature of homomeric and heteromeric glycine receptor channels

Glycine receptors are chloride-permeable, ligand-gated ion channels and contribute to the inhibition of neuronal firing in the central nervous system or to facilitation of neurotransmitter release if expressed at presynaptic sites. Recent structure-function studies provided detailed insights into the mechanisms of channel gating, desensitization and ion permeation. However, most of the work focused only on comparing few isoforms; and amongst studies, different cellular expression systems were used. Here, we performed a series of experiments using recombinantly expressed homomeric and heteromeric glycine receptor channels including their splice variants in the same cellular expression system to investigate and compare their electrophysiological properties. Our data show that the current-voltage relationships of channels formed by the {alpha}2 or {alpha}3 subunits change upon receptor desensitization from a linear to an inwardly-rectifying shape, in contrast to their heteromeric counterparts. We demonstrate that inward rectification depends on a single amino acid (A254) at the inner pore mouth of the channels and is closely linked to chloride permeation. We also show that the current-voltage relationships of glycine-evoked currents in primary hippocampal neurons are inwardly-rectifying upon desensitization. Thus, the alanine residue A254 determines voltage-dependent rectification upon receptor desensitization and provides a physio-molecular signature of homomeric glycine receptor channels which provides unprecedented opportunities for the identification of these channels at the single cell level

Spontaneous Ca(2+) transients in mouse microglia

Microglia are the resident immune cells in the central nervous system and many of their physiological functions are known to be linked to intracellular calcium (Ca2+) signaling. Here we show that isolated and purified mouse microglia-either freshly or cultured-display spontaneous and transient Ca2+ elevations lasting for around ten to twenty seconds and occurring at frequencies of around five to ten events per hour and cell. The events were absent after depletion of internal Ca2+ stores, by phospholipase C (PLC) inhibition or blockade of inositol-1,4,5-trisphosphate receptors (IP3Rs), but not by removal of extracellular Ca2+, indicating that Ca2+ is released from endoplasmic reticulum intracellular stores. We furthermore provide evidence that autocrine ATP release and subsequent activation of purinergic P2Y receptors is not the trigger for these events. Spontaneous Ca2+ transients did also occur after stimulation with Lipopolysaccharide (LPS) and in glioma-associated microglia, but their kinetics differed from control conditions. We hypothesize that spontaneous Ca2+ transients reflect aspects of cellular homeostasis that are linked to regular and patho-physiological functions of microglia

Identification of parvalbumin interneurons as cellular substrate of fear memory persistence

Parvalbumin-positive (PV) basket cells provide perisomatic inhibition in the cortex and hippocampus and control generation of memory-related network activity patterns, such as sharp wave ripples (SPW-R). Deterioration of this class of fast-spiking interneurons has been observed in neuropsychiatric disorders and evidence from animal models suggests their involvement in the acquisition and extinction of fear memories. Here, we used mice with neuron type-targeted expression of the presynaptic gain-of-function glycine receptor RNA variant GlyR {beta}3L(185L) to genetically enhance the network activity of PV interneurons. These mice showed reduced extinction of contextual fear memory but normal auditory cued fear memory. They furthermore displayed increase of SPW-R activity in area CA3 and CA1 and facilitated propagation of this particular network activity pattern, as determined in ventral hippocampal slice preparations. Individual freezing levels during extinction and SPW-R propagation were correlated across genotypes. The same was true for parvalbumin immunoreactivity in the ventral hippocampus, which was generally augmented in the GlyR mutant mice and correlated with individual freezing levels. Together, these results identify PV interneurons as critical cellular substrate of fear memory persistence and associated SPW-R activity in the hippocampus. Our findings may be relevant for the identification and characterization of physiological correlates for posttraumatic stress and anxiety disorders

Equatorial currents and transports in the upper central Indian Ocean: Annual cycle and interannual variability

The zonal circulation south of Sri Lanka is an important link for the exchange of water between the Bay of Bengal and the Arabian Sea. Results from a first array of three moorings along 80 degrees 30'E north of 4 degrees 10'N from January .1991 to March 1992 were used to investigate the Monsoon Current regime [Schott et al., 1994]. Measurements from a second array of six current meter moorings are presented here. This array was deployed along 80 degrees 30'E between 45'S and 5 degrees N from July 1993 to September 1994 to investigate the annual cycle and interannual variability of the equatorial currents at this longitude. Both sets of moorings contribute to the Indian Ocean current meter array ICM8 of the World Ocean Circulation Experiment. The semiannual equatorial jet (EJ) was showing a large seasonal asymmetry, reaching a monthly mean eastward transport of 35 Sv (1 Sv = 1 x 10(6) m(3) s(-1)) in November 1993, but just 5 Sv in May 1994. The Equatorial Undercurrent (EUC) had a maximum transport of 17 Sv in March to April 1994. Unexpectedly, compared to previous observations and model studies, the EUC was reappearing again in August 1994 at more than 10 Sv transport and was still flowing when the moorings were recovered. In addition, monthly mean ship drifts near the equator are evaluated to support the interpretation of the moored observations. Interannual variability of the EJ in our measurements and ship drift data appears to be related to the variability of the zonal winds and Southern Oscillation Index. The output of a global numerical model (Parallel Ocean Climate Model) driven by the winds for 1993/1994 is used to connect our observations to the larger scale. The model reproduces the EJ asymmetry and shows the existence of the EUC and its reappearance during summer 1994

Deep currents and the eastward salinity tongue in the equatorial Atlantic: Results from an eddy-resolving, primitive equation model

The high-resolution model of the wind-driven and thermohaline circulation in the Atlantic Ocean developed in recent years as a “community modeling effort” for the World Ocean Circulation Experiment is examined for the temporal and spatial structure of the deep equatorial current field and its effect on the spreading of North Atlantic Deep Water (NADW). Under seasonally varying wind forcing, the model reveals a system of basin-wide zonal currents of O(5 cm s−1), alternating east-west, and oscillating at an annual period. The current fluctuations are induced by the seasonal cycle of the wind stress in the equatorial Atlantic and show characteristics of long equatorial Rossby waves with westward phase propagation of about 15 cm s−1. The mean flow in the deep western tropical Atlantic is governed by a deep western boundary current (DWBC) with core velocities of more than 10 cm s−1. Only a small fraction of the DWBC branches off at the equator, with correspondingly low mean eastward currents of only about 1 cm s−1. Despite this weak advection along the equator, a well-developed salinity tongue is observed in the model, which is reminiscent of observed property distributions at the upper NADW level. The model evaluation indicates the salinity pattern to be a result of a balance between mean zonal advection and meridional diffusion of salt. The presence of the zonal current oscillations appears to have no significance for the existence of the salinity tongue