Encoding the Timing of Inhibitory Inputs

2005 ◽  
Vol 93 (5) ◽  
pp. 2887-2897 ◽  
Author(s):  
Patrick O. Kanold ◽  
Paul B. Manis
Keyword(s):  
Spike Timing ◽  
Dorsal Cochlear Nucleus ◽  
Heterogeneous Distribution ◽  
Information Encoding ◽  
Neuronal Populations ◽  
Voltage Change ◽  
Voltage Dependent ◽  
Inhibitory Potential ◽  
Neuronal Systems

Many neuronal systems represent information by the timing of individual spikes, and it is generally assumed that spike timing predominantly encodes excitatory inputs. We show here that the timing of inhibition can also be explicitly encoded in spike times using time-dependent and voltage-dependent properties of a rapidly inactivating potassium channel ( IKIF). In vitro recordings in rat dorsal cochlear nucleus show that the effects of inhibition on spike timing can long outlast the duration of the inhibitory potential and that this depends only on the membrane voltage change during the inhibitory postsynaptic potential. Modeling results show that small neuronal populations with a heterogeneous distribution of IKIF voltage dependence can robustly encode intervals of >100 ms between inhibition and excitation. Thus neuronal systems can detect and represent the precise timing of inhibition, suggesting the importance of inhibition in information encoding.

scholarly journals An axon initial segment is required for temporal precision in action potential encoding by neuronal populations

2018 ◽  
Vol 4 (11) ◽  
pp. eaau8621 ◽  
Author(s):  
Elinor Lazarov ◽  
Melanie Dannemeyer ◽  
Barbara Feulner ◽  
Jörg Enderlein ◽  
Michael J. Gutnick ◽  
...  
Keyword(s):  
Initial Segment ◽  
Axon Initial Segment ◽  
High Concentration ◽  
Information Encoding ◽  
Temporal Precision ◽  
Network Function ◽  
Evolutionary Innovation ◽  
Voltage Dependent ◽  
Vitro Model

Central neurons initiate action potentials (APs) in the axon initial segment (AIS), a compartment characterized by a high concentration of voltage-dependent ion channels and specialized cytoskeletal anchoring proteins arranged in a regular nanoscale pattern. Although the AIS was a key evolutionary innovation in neurons, the functional benefits it confers are not clear. Using a mutation of the AIS cytoskeletal protein βIV-spectrin, we here establish an in vitro model of neurons with a perturbed AIS architecture that retains nanoscale order but loses the ability to maintain a high NaV density. Combining experiments and simulations, we show that a high NaV density in the AIS is not required for axonal AP initiation; it is, however, crucial for a high bandwidth of information encoding and AP timing precision. Our results provide the first experimental demonstration of axonal AP initiation without high axonal channel density and suggest that increasing the bandwidth of the neuronal code and, hence, the computational efficiency of network function, was a major benefit of the evolution of the AIS.

scholarly journals Background Synaptic Conductance and Precision of EPSP-Spike Coupling at Pyramidal Cells

2005 ◽  
Vol 93 (6) ◽  
pp. 3248-3256 ◽  
Author(s):  
Veronika Zsiros ◽  
Shaul Hestrin
Keyword(s):  
Time Course ◽  
Pyramidal Cells ◽  
Spike Timing ◽  
Synaptic Activity ◽  
Synaptic Conductance ◽  
Temporal Precision ◽  
Voltage Dependent ◽  
Cortical Slices

The temporal precision of converting excitatory postsynaptic potentials (EPSPs) into spikes at pyramidal cells is critical for the coding of information in the cortex. Several in vitro studies have shown that voltage-dependent conductances in pyramidal cells can prolong the EPSP time course resulting in an imprecise EPSP-spike coupling. We have used dynamic-clamp techniques to mimic the in vivo background synaptic conductance in cortical slices and investigated how the ongoing synaptic activity may affect the EPSP time course near threshold and the EPSP spike coupling. We report here that background synaptic conductance dramatically diminished the depolarization related prolongation of the EPSPs in pyramidal cells and improved the precision of spike timing. Furthermore, we found that background synaptic conductance can affect the interaction among action potentials in a spike train. Thus the level of ongoing synaptic activity in the cortex may regulate the capacity of pyramidal cells to process temporal information.

scholarly journals Action Potential Timing Precision in Dorsal Cochlear Nucleus Pyramidal Cells

2007 ◽  
Vol 97 (6) ◽  
pp. 4162-4172 ◽  
Author(s):  
Sarah E. Street ◽  
Paul B. Manis
Keyword(s):  
Firing Rate ◽  
Cochlear Nucleus ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Spike Trains ◽  
Spike Timing ◽  
Dorsal Cochlear Nucleus ◽  
Information Encoding ◽  
Temporal Precision ◽  
Noise Current

Many studies of the dorsal cochlear nucleus (DCN) have focused on the representation of acoustic stimuli in terms of average firing rate. However, recent studies have emphasized the role of spike timing in information encoding. We sought to ascertain whether DCN pyramidal cells might employ similar strategies and to what extent intrinsic excitability regulates spike timing. Gaussian distributed low-pass noise current was injected into pyramidal cells in a brain slice preparation. The shuffled autocorrelation-based analysis was used to compute a correlation index of spike times across trials. The noise causes the cells to fire with temporal precision (SD ≅ 1–2 ms) and high reproducibility. Increasing the coefficient of variation of the noise improved the reproducibility of the spike trains, whereas increasing the firing rate of the neuron decreased the neurons' ability to respond with predictable patterns of spikes. Simulated inhibitory postsynaptic potentials superimposed on the noise stimulus enhanced spike timing for >300 ms, although the enhancement was greatest during the first 100 ms. We also found that populations of pyramidal neurons respond to the same noise stimuli with correlated spike trains, suggesting that ensembles of neurons in the DCN receiving shared input can fire with similar timing. These results support the hypothesis that spike timing can be an important aspect of information coding in the DCN.

An Attempt at Biological Control of Blossom Blight of Rose Caused by Botrytis cinerea Using some Local Trichoderma spp. Strains

2020 ◽  
Vol 55 (1) ◽  
pp. 27-34
Author(s):  
G. Zadehdabagh ◽  
K. Karimi ◽  
M. Rezabaigi ◽  
F. Ajamgard
Keyword(s):  
Botrytis Cinerea ◽  
Mycelial Growth ◽  
Limiting Factor ◽  
Dual Culture ◽  
Trichoderma Spp ◽  
Khuzestan Province ◽  
Inhibitory Potential ◽  
Cut Rose

The northern of Khuzestan province in Iran is mainly considered as one of the major areas of miniature rose production. Blossom blight caused by Botrytis cinerea has recently become a serious limiting factor in rose production in pre and post-harvest. In current study, an attempt was made to evaluate the inhibitory potential of some local Trichoderma spp. strains against B. cinerea under in vitro and in vivo conditions. The in vitro results showed that all Trichoderma spp. strains were significantly able to reduce the mycelial growth of the pathogen in dual culture, volatile and non-volatile compounds tests compared with control, with superiority of T. atroviride Tsafi than others. Under in vivo condition, the selected strain of T. atroviride Tsafi had much better performance than T. harzianum IRAN 523C in reduction of disease severity compared with the untreated control. Overall, the findings of this study showed that the application of Trichoderma-based biocontrol agents such as T. atroviride Tsafi can be effective to protect cut rose flowers against blossom blight.

Drug Design of Inhibitors of Alzheimer’s Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives

2019 ◽  
Vol 19 (8) ◽  
pp. 688-705
Author(s):  
Taibi Ben Hadda ◽  
Abdur Rauf ◽  
Hsaine Zgou ◽  
Fatma Sezer Senol ◽  
Ilkay Erdogan Orhan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Metal Accumulation ◽  
Microtiter Plate ◽  
Metal Chelation ◽  
Carbonyl Derivatives ◽  
Cholinesterase Inhibitory Activity ◽  
Inhibitory Potential

Background:Since deficit of acetylcholine has been evidenced in the Alzheimer’s disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD.Method:In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 μg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity.Results and Conclusion:All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good harmonization with experimental data.

Inhibition of dihydropyridine-sensitive calcium entry in hypoxic relaxation of airway smooth muscle

1995 ◽  
Vol 268 (2) ◽  
pp. L201-L206 ◽  
Author(s):  
C. Vannier ◽  
T. L. Croxton ◽  
L. S. Farley ◽  
C. A. Hirshman
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Bay K 8644 ◽  
O2 Concentration ◽  
Voltage Dependent ◽  
Progressive Hypoxia ◽  
Carbamyl Choline

Hypoxia dilates airways in vivo and reduces active tension of airway smooth muscle in vitro. To determine whether hypoxia impairs Ca2+ entry through voltage-dependent channels (VDC), we tested the ability of dihydropyridines to modulate hypoxia-induced relaxation of KCl- and carbamyl choline (carbachol)-contracted porcine bronchi. Carbachol- or KCl-contracted bronchial rings were exposed to progressive hypoxia in the presence or absence of 1 microM BAY K 8644 (an L-type-channel agonist). In separate experiments, rings were contracted with carbachol or KCl, treated with nifedipine (a VDC antagonist), and finally exposed to hypoxia. BAY K 8644 prevented hypoxia-induced relaxation in KCl-contracted bronchi. Nifedipine (10(-5) M) totally relaxed KCl- contracted bronchi. Carbachol-contracted bronchi were only partially relaxed by nifedipine but were completely relaxed when the O2 concentration of the gas was reduced from 95 to 0%. These data indicate that hypoxia can reduce airway smooth muscle tone by limiting entry of Ca2+ through a dihydropyridine-sensitive pathway, but that other mechanisms also contribute to hypoxia-induced relaxation of carbachol-contracted bronchi.

scholarly journals The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 873
Author(s):  
Raphael J. Eberle ◽  
Danilo S. Olivier ◽  
Marcos S. Amaral ◽  
Ian Gering ◽  
Dieter Willbold ◽  
...  
Keyword(s):  
Binding Mode ◽  
Drug Candidates ◽  
Main Protease ◽  
Ic50 Values ◽  
Repurposed Drugs ◽  
Antiparasitic Drugs ◽  
Inhibitory Potential ◽  
Dynamics Simulations ◽  
Micromolar Range

Since the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude. To date, several clinically safe and efficient vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs for emergency use have been approved. However, increasing numbers of SARS-Cov-2 variants make it imminent to identify an alternative way to treat SARS-CoV-2 infections. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is repurposing clinically developed drugs, e.g., antiparasitic drugs. The results described in this study demonstrated the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CLpro). Quinacrine and suramin molecules presented a competitive and noncompetitive inhibition mode, respectively, with IC50 values in the low micromolar range. Surface plasmon resonance (SPR) experiments demonstrated that quinacrine and suramin alone possessed a moderate or weak affinity with SARS-CoV-2 3CLpro but suramin binding increased quinacrine interaction by around a factor of eight. Using docking and molecular dynamics simulations, we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin, in combination with quinacrine, showed promising synergistic efficacy to inhibit SARS-CoV-2 3CLpro. We suppose that the identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease and repurposable drug candidates offer fast therapeutic breakthroughs, mainly in a pandemic moment.

Sign in / Sign up

Export Citation Format

Share Document