scholarly journals Cone-driven retinal responses are shaped by rod but not cone HCN1

2021 ◽  
Author(s):  
Colten Lankford ◽  
Yumiko Umino ◽  
Deepak Poria ◽  
Vladimir Kefalov ◽  
Eduardo Solessio ◽  
...  
Keyword(s):  
Light Intensity ◽  
Dynamic Range ◽  
Temporal Frequency ◽  
Complex Function ◽  
Conditional Knockout ◽  
Voltage Response ◽  
Membrane Hyperpolarization ◽  
Relative Contribution ◽  
High Level ◽  
Hcn1 Channels

Signal integration of converging neural circuits is poorly understood. One example is in the retina where the integration of rod and cone signaling is responsible for the large dynamic range of vision. The relative contribution of rods versus cones is dictated by a complex function involving background light intensity and stimulus temporal frequency. One understudied mechanism involved in coordinating rod and cone signaling onto the shared retinal circuit is the hyperpolarization activated current (Ih) mediated by HCN1 channels. Ih opposes membrane hyperpolarization driven by activation of the phototransduction cascade and modulates the strength and kinetics of the photoreceptor voltage response. We examined conditional knockout of HCN1 from rods using electroretinography. In the absence of HCN1, rod responses are prolonged in dim light which altered the response to slow modulation of light intensity both at the level of retinal signaling and behavior. Under brighter intensities, cone-driven signaling was suppressed. To our surprise, conditional knockout of HCN1 from cones had no effect on cone-mediated signaling. We propose that Ih is dispensable in cones due to the high level of temporal control of cone phototransduction. Thus, HCN1 is required for cone-driven retinal signaling only indirectly by modulating the voltage response of rods to limit their output.

scholarly journals Forebrain HCN1 Channels Contribute to Hypnotic Actions of Ketamine

2013 ◽  
Vol 118 (4) ◽  
pp. 785-795 ◽  
Author(s):  
Cheng Zhou ◽  
Jennifer E. Douglas ◽  
Natasha N. Kumar ◽  
Shaofang Shu ◽  
Douglas A. Bayliss ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Pyramidal Neurons ◽  
Conditional Knockout ◽  
Membrane Properties ◽  
Membrane Hyperpolarization ◽  
Loss Of Righting Reflex ◽  
Neural Substrate ◽  
Righting Reflex ◽  
Mechanistic Basis ◽  
Hcn1 Channels

Abstract Background: Ketamine is a commonly used anesthetic, but the mechanistic basis for its clinically relevant actions remains to be determined. The authors previously showed that HCN1 channels are inhibited by ketamine and demonstrated that global HCN1 knockout mice are twofold less sensitive to hypnotic actions of ketamine. Although that work identified HCN1 channels as a viable molecular target for ketamine, it did not determine the relevant neural substrate. Methods: To localize the brain region responsible for HCN1-mediated hypnotic actions of ketamine, the authors used a conditional knockout strategy to delete HCN1 channels selectively in excitatory cells of the mouse forebrain. A combination of molecular, immunohistochemical, and cellular electrophysiologic approaches was used to verify conditional HCN1 deletion; a loss-of-righting reflex assay served to ascertain effects of forebrain HCN1 channel ablation on hypnotic actions of ketamine. Results: In conditional knockout mice, HCN1 channels were selectively deleted in cortex and hippocampus, with expression retained in cerebellum. In cortical pyramidal neurons from forebrain-selective HCN1 knockout mice, effects of ketamine on HCN1-dependent membrane properties were absent; notably, ketamine was unable to evoke membrane hyperpolarization or enhance synaptic inputs. Finally, the EC50 for ketamine-induced loss-of-righting reflex was shifted to significantly higher concentrations (by approximately 31%). Conclusions: These data indicate that forebrain principal cells represent a relevant neural substrate for HCN1-mediated hypnotic actions of ketamine. The authors suggest that ketamine inhibition of HCN1 shifts cortical neuron electroresponsive properties to contribute to ketamine-induced hypnosis.

scholarly journals Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects

2020 ◽  
Vol 21 (24) ◽  
pp. 9763
Author(s):  
Qing-Rong Liu ◽  
Ana Canseco-Alba ◽  
Ying Liang ◽  
Hiroki Ishiguro ◽  
Emmanuel S. Onaivi
Keyword(s):  
Cortical Neurons ◽  
Cannabinoid Receptors ◽  
Dynamic Range ◽  
Conditional Knockout ◽  
Dopamine Neurons ◽  
In Vivo Studies ◽  
Mouse Strains ◽  
Genotypic Differences ◽  
Mrna Levels ◽  
Selective Agonist

There are two well-characterized cannabinoid receptors (CB1R and CB2R and other candidates): the central nervous system (CNS) enriched CB1R and peripheral tissue enriched CB2R with a wide dynamic range of expression levels in different cell types of human tissues. Hepatocytes and neurons express low baseline CB1R and CB2R, respectively, and their cell-type-specific functions are not well defined. Here we report inducible expression of CB1R in the liver by high-fat and high sugar diet and CB2R in cortical neurons by methamphetamine. While there is less controversy about hepatocyte CB1R, the presence of functional neuronal CB2R is still debated to date. We found that neuron CB2R basal expression was higher than that of hepatocyte CB1R by measuring mRNA levels of specific isoform CB2A in neurons isolated by fluorescence-activated cell sorting (FACS) and CB1A in hepatocytes isolated by collagenase perfusion of liver. For in vivo studies, we generated hepatocyte, dopaminergic neuron, and microglia-specific conditional knockout mice (Abl-Cnr1Δ, Dat-Cnr2Δ, and Cx3cr1-Cnr2Δ) of CB1R and CB2R by crossing Cnr1f/f and Cnr2f/f strains to Abl-Cre, Dat-Cre, and Cx3cr1-Cre deleter mouse strains, respectively. Our data reveals that neuron and microglia CB2Rs are involved in the “tetrad” effects of the mixed agonist WIN 55212-2, CB1R selective agonist arachidonyl-2′-chloroethylamide (ACEA), and CB2R selective agonist JWH133. Dat-Cnr2Δ and Cx3cr1-Cnr2Δ mice showed genotypic differences in hypomobility, hypothermia, analgesia, and catalepsy induced by the synthetic cannabinoids. Alcohol conditioned place preference was abolished in DAT-Cnr2Δ mice and remained intact in Cx3cr1-Cnr2Δ mice in comparison to WT mice. These Cre-loxP recombinant mouse lines provide unique approaches in cannabinoid research for dissecting the complex endocannabinoid system that is implicated in many chronic disorders.

An adaptive Reichardt detector model of motion adaptation in insects and mammals

1997 ◽  
Vol 14 (4) ◽  
pp. 741-749 ◽  
Author(s):  
Colin W.G. Clifford ◽  
Michael R. Ibbotson ◽  
Keith Langley
Keyword(s):  
Dynamic Range ◽  
Frequency Tuning ◽  
Temporal Frequency ◽  
Optic Tract ◽  
Intrinsic Property ◽  
Wide Field ◽  
Motion Adaptation ◽  
Motion Sensitivity ◽  
Differential Motion ◽  
Motion Detectors

AbstractThere are marked similarities in the adaptation to motion observed in wide-field directional neurons found in the mammalian nucleus of the optic tract and cells in the insect lobula plate. However, while the form and time scale of adaptation is comparable in the two systems, there is a difference in the directional properties of the effect. A model based on the Reichardt detector is proposed to describe adaptation in mammals and insects, with only minor modifications required to account for the differences in directionality. Temporal-frequency response functions of the neurons and the model are shifted laterally and compressed by motion adaptation. The lateral shift enhances dynamic range and differential motion sensitivity. The compression is not caused by fatigue, but is an intrinsic property of the adaptive process resulting from interdependence of temporal-frequency tuning and gain in the temporal filters of the motion detectors.

scholarly journals First multispacecraft ion measurements in and near the Earth’s magnetosphere with the identical Cluster ion spectrometry (CIS) experiment

2001 ◽  
Vol 19 (10/12) ◽  
pp. 1303-1354 ◽  
Author(s):  
H. Rème ◽  
C. Aoustin ◽  
J. M. Bosqued ◽  
I. Dandouras ◽  
B. Lavraud ◽  
...  
Keyword(s):  
Solar Wind ◽  
Angular Resolution ◽  
Dynamic Range ◽  
Ion Beam ◽  
Three Dimensional ◽  
Charge Composition ◽  
Ion Distribution ◽  
Central Plasma ◽  
Cluster Ion ◽  
High Level

Abstract. On board the four Cluster spacecraft, the Cluster Ion Spectrometry (CIS) experiment measures the full, three-dimensional ion distribution of the major magnetospheric ions (H+, He+, He++, and O+) from the thermal energies to about 40 keV/e. The experiment consists of two different instruments: a COmposition and DIstribution Function analyser (CIS1/CODIF), giving the mass per charge composition with medium (22.5°) angular resolution, and a Hot Ion Analyser (CIS2/HIA), which does not offer mass resolution but has a better angular resolution (5.6°) that is adequate for ion beam and solar wind measurements. Each analyser has two different sensitivities in order to increase the dynamic range. First tests of the instruments (commissioning activities) were achieved from early September 2000 to mid January 2001, and the operation phase began on 1 February 2001. In this paper, first results of the CIS instruments are presented showing the high level performances and capabilities of the instruments. Good examples of data were obtained in the central plasma sheet, magnetopause crossings, magnetosheath, solar wind and cusp measurements. Observations in the auroral regions could also be obtained with the Cluster spacecraft at radial distances of 4–6 Earth radii. These results show the tremendous interest of multispacecraft measurements with identical instruments and open a new area in magnetospheric and solar wind-magnetosphere interaction physics.Key words. Magnetospheric physics (magnetopause, cusp and boundary layers; magnetopheric configuration and dynamics; solar wind - magnetosphere interactions)

scholarly journals Attribution of Atmospheric Sulfur Dioxide over the English Channel to Dimethylsulfide and Changing Ship Emissions

2016 ◽  
Author(s):  
Mingxi Yang ◽  
Thomas G. Bell ◽  
Frances E. Hopkins ◽  
Timothy J. Smyth
Keyword(s):  
Sulfur Dioxide ◽  
English Channel ◽  
Relative Contribution ◽  
Fold Reduction ◽  
Atmospheric Sulfur ◽  
Atmospheric Sulfur Dioxide ◽  
Carbon Dioxide Co2 ◽  
High Level ◽  
Marine Air ◽  
Sulfur Emissions

Abstract. Atmospheric sulfur dioxide (SO2) was measured continuously from the Penlee Point Atmospheric Observatory(PPAO) near Plymouth, United Kingdom between May 2014 and November 2015. This coastal site is exposed to marine air across a wide wind sector. The predominant southwesterly winds carry relatively clean background Atlantic air. In contrast, air from the southeast is heavily influenced by exhaust plumes from ships in the English Channel as well as near the Plymouth Sound. New International Maritime Organization (IMO) regulation came into force in January 2015 to reduce sulfur emissions tenfold in Sulfur Emission Control Areas such as the English Channel. Our observations suggest a three-fold reduction from 2014 to 2015 in ship-emitted SO2 from that direction. Apparent fuel sulfur content calculated from coincidental SO2 and carbon dioxide (CO2) peaks from local ship plum es show a high level of compliance to the IMO regulation (> 95 %) in both years. Dimethylsulfide (DMS) is an important source of atmospheric SO2 even in this semi-polluted region. The relative contribution of DMS oxidation to the SO2 burden over the English Channel increased from ~ 1/3 in 2014 to ~ 1/2 in 2015 due to the reduction in ship sulfur emissions. Our diel analysis suggests that SO2 is removed from the marine atmospheric boundary layer in about half a day, with dry deposition to the ocean accounting for a quarter of the total loss.

Fluorescence principles and measurement

2000 ◽  
Author(s):  
Arthur G. Szabo
Keyword(s):  
Fluorescence Spectroscopy ◽  
Single Molecule ◽  
Dynamic Range ◽  
Spectroscopic Method ◽  
Energy Difference ◽  
Visible Spectral Range ◽  
Analytical Determination ◽  
Whole Cells ◽  
Genomic Characterization ◽  
High Level

Fluorescence spectrometry is the most extensively used optical spectroscopic method in analytical measurement and scientific investigation. During the past five years more than 60000 scientific articles have been published in which fluorescence spectroscopy has been used. The large number of applications ranges from the analytical determination of trace metals in the environment to pH measurements in whole cells under physiological conditions. In the scientific research laboratory, fluorescence spectroscopy is being used or applied to study the fundamental physical processes of molecules; structure-function relationships and interactions of biomolecules such as proteins and nucleic acids; structures and activity within whole cells using such instrumentation as confocal microscopy; and DNA sequencing in genomic characterization. In analytical applications the use of fluorescence is dominant in clinical laboratories where fluorescence immunoassays have largely replaced radioimmunoassay techniques. There are two main reasons for this extensive use of fluorescence spectroscopy. Foremost is the high level of sensitivity and wide dynamic range that can be achieved. There are a large number of laboratories that have reported single molecule detection. Secondly, the instrumentation required is convenient and for most purposes can be purchased at a modest cost. While improvements and advances continue to be reported fluorescence instrumentation has reached a high level of maturity. A review of the physical principles of the fluorescence phenomenon permits one to understand the origins of the information content that fluorescence measurements can provide. A molecule absorbs electromagnetic radiation through a quantum mechanical process where the molecule is transformed from a ‘ground’ state to an ‘excited’ state. The energy of the absorbed photon of light corresponds to the energy difference between these two states. In the case of light in the ultraviolet and visible spectral range of 200 nm to 800 nm that corresponds to energies of 143 to 35.8 kcal mol-1. The absorption of light results in an electronic transition in the atom or molecule. In atoms this involves the promotion of an electron from an outer shell orbital to an empty orbital of higher energy.

Interactions of Light, Temperature and Moisture on Terbutryn Toxicity

Weed Science ◽  
1971 ◽  
Vol 19 (6) ◽  
pp. 732-735 ◽  
Author(s):  
L. D. Houseworth ◽  
B. G. Tweedy
Keyword(s):  
Light Intensity ◽  
Cucumis Sativus ◽  
Environmental Conditions ◽  
Rapid Growth ◽  
Field Capacity ◽  
Moisture Level ◽  
Low Level ◽  
High Level

Toxicity of soil-applied 2-(tert-butylamino)-4-(ethylamino)-6-(methylthio)-s-triazine (terbutryn) to cucumbers (Cucumis sativusL. ‘Gemni’) and oats (Avena sativusL. ‘Nodaway’) was increased 2.2 times when the light intensity was raised from 11,000 to 22,000 lumens/m2and 1.5 times when the moisture level was raised from low (25 to 50% field capacity) to high (75 to 100% field capacity). When the temperature was raised from the low level (19 C day, 14 C night) to the high level (29 C day, 24 C night) toxicity of terbutryn to oats was increased 1.6 times and toxicity to cucumber was increased 1.3 times. Analysis of interactions of the three variables on toxicity of terbutryn showed that environmental conditions favoring rapid growth resulted in an increase in phytotoxicity.

Contrast encoding in retinal bipolar cells: Current vs. voltage

2003 ◽  
Vol 20 (1) ◽  
pp. 19-28 ◽  
Author(s):  
WALLACE B. THORESON ◽  
DWIGHT A. BURKHARDT
Keyword(s):  
Dynamic Range ◽  
Linear Regression Analysis ◽  
Bipolar Cells ◽  
Response Analysis ◽  
Voltage Response ◽  
Cone Voltage ◽  
Current Response ◽  
Contrast Gain ◽  
Retinal Bipolar Cells ◽  
Contrast Response

To investigate the influence of voltage-sensitive conductances in shaping light-evoked responses of retinal bipolar cells, whole-cell recordings were made in the slice preparation of the tiger salamander, Ambystoma tigrinum. To study contrast encoding, the retina was stimulated with 0.5-s steps of negative and positive contrasts of variable magnitude. In the main, responses recorded under voltage- and current-clamp modes were remarkably similar. In general agreement with past results in the intact retina, the contrast/response curves were relatively steep for small contrasts, thus showing high contrast gain; the dynamic range was narrow, and responses tended to saturate at relatively small contrasts. For ON and OFF cells, linear regression analysis showed that the current response accounted for 83–93% of the variance of the voltage response. Analysis of specific parameters of the contrast/response curve showed that contrast gain was marginally higher for voltage than current in three of four cases, while no significant differences were found for half-maximal contrast (C50), dynamic range, or contrast dominance. In sum, the overall similarity between current and voltage responses indicates that voltage-sensitive conductances do not play a major role in determining the shape of the bipolar cell's contrast response in the light-adapted retina. The salient characteristics of the contrast response of bipolars apparently arise between the level of the cone voltage response and the postsynaptic current of bipolar cells, via the transformation between cone voltage and transmitter release and/or via the interaction between the neurotransmitter glutamate and its postsynaptic receptors on bipolar cells.

scholarly journals Genome Evolution at the Genus Level: Comparison of Three Complete Genomes of Hyperthermophilic Archaea

2001 ◽  
Vol 11 (6) ◽  
pp. 981-993
Author(s):  
Odile Lecompte ◽  
Raymond Ripp ◽  
Valérie Puzos-Barbe ◽  
Simone Duprat ◽  
Roland Heilig ◽  
...  
Keyword(s):  
Pyrococcus Furiosus ◽  
Hyperthermophilic Archaea ◽  
Trna Genes ◽  
Distance Ratio ◽  
Genomic Plasticity ◽  
Relative Contribution ◽  
Complete Genomes ◽  
Replication Terminus ◽  
Living Organisms ◽  
High Level

We have compared three complete genomes of closely related hyperthermophilic species of Archaea belonging to thePyrococcus genus: Pyrococcus abyssi, Pyrococcus horikoshii, and Pyrococcus furiosus. At the genomic level, the comparison reveals a differential conservation among four regions of the Pyrococcus chromosomes correlated with the location of genetic elements mediating DNA reorganization. This discloses the relative contribution of the major mechanisms that promote genomic plasticity in these Archaea, namely rearrangements linked to the replication terminus, insertion sequence-mediated recombinations, and DNA integration within tRNA genes. The combination of these mechanisms leads to a high level of genomic plasticity in these hyperthermophilic Archaea, at least comparable to the plasticity observed between closely related bacteria. At the proteomic level, the comparison of the threePyrococcus species sheds light on specific selection pressures acting both on their coding capacities and evolutionary rates. Indeed, thanks to two independent methods, the “reciprocal best hits“ approach and a new distance ratio analysis, we detect the false orthology relationships within the Pyrococcus lineage. This reveals a high amount of differential gains and losses of genes since the divergence of the three closely related species. The resulting polymorphism is probably linked to an adaptation of these free-living organisms to differential environmental constraints. As a corollary, we delineate the set of orthologous genes shared by the three species, that is, the genes that may characterize the Pyrococcus genus. In this conserved core, the amino acid substitution rate is equal between P. abyssi and P. horikoshii for most of their shared proteins, even for fast-evolving ones. In contrast, strong discrepancies exist among the substitution rates observed in P. furiosus relative to the two other species, which is in disagreement with the molecular clock hypothesis.

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