Optimal Inputs for Phase Models of Spiking Neurons

2006 ◽  
Vol 1 (4) ◽  
pp. 358-367 ◽  
Author(s):  
Jeff Moehlis ◽  
Eric Shea-Brown ◽  
Herschel Rabitz
Keyword(s):  
Time Course ◽  
Phase Response Curve ◽  
Spiking Neurons ◽  
Neural Dynamics ◽  
Neural Oscillator ◽  
Neural Models ◽  
Optimal Inputs ◽  
Integral Measure ◽  
Phase Models

Variational methods are used to determine the optimal currents that elicit spikes in various phase reductions of neural oscillator models. We show that, for a given reduced neuron model and target spike time, there is a unique current that minimizes a square-integral measure of its amplitude. For intrinsically oscillatory models, we further demonstrate that the form and scaling of this current is determined by the model’s phase response curve. These results reflect the role of intrinsic neural dynamics in determining the time course of synaptic inputs to which a neuron is optimally tuned to respond, and are illustrated using phase reductions of neural models valid near typical bifurcations to periodic firing, as well as the Hodgkin-Huxley equations.

Charge-Balanced Optimal Inputs for Phase Models of Spiking Neurons

2009 ◽  
Author(s):  
Ali Nabi ◽  
Jeff Moehlis
Keyword(s):  
Time Horizon ◽  
Neuron Model ◽  
Spiking Neurons ◽  
Input Current ◽  
Input Energy ◽  
Charge Balance ◽  
Specific Target ◽  
Optimal Inputs ◽  
Total Input ◽  
Phase Models

The optimal input current for a reduced neuron model and a specific target spiking time is obtained. The objective of optimization is to minimize the total input energy to the system subject to a zero net input integral over the time horizon. This “charge-balance constraint” ensures that no net external charge is injected into the neuron. The results are compared to optimal currents for which the charge-balance constraint is not imposed.

scholarly journals Neurons as oscillators

2016 ◽  
Vol 116 (6) ◽  
pp. 2950-2960 ◽  
Author(s):  
Klaus M. Stiefel ◽  
G. Bard Ermentrout
Keyword(s):  
Time Course ◽  
Phase Response Curve ◽  
Neuronal Firing ◽  
Spiking Neurons ◽  
Network Activity ◽  
Neural Population ◽  
Spiking Neuron ◽  
Network Behavior ◽  
Small Perturbations ◽  
Systems Neuroscience

Regularly spiking neurons can be described as oscillators. In this article we review some of the insights gained from this conceptualization and their relevance for systems neuroscience. First, we explain how a regularly spiking neuron can be viewed as an oscillator and how the phase-response curve (PRC) describes the response of the neuron's spike times to small perturbations. We then discuss the meaning of the PRC for a single neuron's spiking behavior and review the PRCs measured from a variety of neurons in a range of spiking regimes. Next, we show how the PRC can be related to a number of common measures used to quantify neuronal firing, such as the spike-triggered average and the peristimulus histogram. We further show that the response of a neuron to correlated inputs depends on the shape of the PRC. We then explain how the PRC of single neurons can be used to predict neural network behavior. Given the PRC, conduction delays, and the waveform and time course of the synaptic potentials, it is possible to predict neural population behavior such as synchronization. The PRC also allows us to quantify the robustness of the synchronization to heterogeneity and noise. We finally ask how to combine the measured PRCs and the predictions based on PRC to further the understanding of systems neuroscience. As an example, we discuss how the change of the PRC by the neuromodulator acetylcholine could lead to a destabilization of cortical network dynamics. Although all of these studies are grounded in mathematical abstractions that do not strictly hold in biology, they provide good estimates for the emergence of the brain's network activity from the properties of individual neurons. The study of neurons as oscillators can provide testable hypotheses and mechanistic explanations for systems neuroscience.

Collagen-Induced Platelet Aggregation: -Evidence Against the Essential Role of Platelet Adenosine Diphosphate

1979 ◽  
Vol 42 (04) ◽  
pp. 1193-1206 ◽  
Author(s):  
Barbara Nunn
Keyword(s):  
Platelet Aggregation ◽  
Time Course ◽  
Essential Role ◽  
Atp Release ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
High Doses ◽  
Induced Aggregation

SummaryThe hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 μM ADP, were not inhibited by 500 pM adenosine, a concentration that greatly reduced the effect of 300 μM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.

scholarly journals Decoding the temporal nature of brain GR activity in the NFκB signal transition leading to depressive-like behavior

2021 ◽  
Author(s):  
Young-Min Han ◽  
Min Sun Kim ◽  
Juyeong Jo ◽  
Daiha Shin ◽  
Seung-Hae Kwon ◽  
...  
Keyword(s):  
Inhibitory Action ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Late Phase ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Middle Phase ◽  
Temporal Shift

AbstractThe fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.

Role of Saliva in Caries Models

1995 ◽  
Vol 9 (3) ◽  
pp. 235-238 ◽  
Author(s):  
W.M. Edgar ◽  
S.M. Higham
Keyword(s):  
Design Of Experiments ◽  
Crucial Role ◽  
Time Course ◽  
Therapeutic Agents ◽  
White Spot ◽  
Protective Effects ◽  
White Spot Lesions ◽  
Dynamic Effects ◽  
Full Expression

The crucial role played by the actions of saliva in controlling the equilibrium between de- and remineralization in a cariogenic environment is demonstrated by the effects on caries incidence of salivary dysfunction and by the distribution of sites of caries predilection to those where salivary effects are restricted. However, of the several properties of saliva which may confer protective effects, it is not certain which are most important. A distinction can be made between static protective effects, which act continuously, and dynamic effects, which act during the time-course of the Stephan curve. Evidence implicates salivary buffering and sugar clearance as important dynamic effects of saliva to prevent demineralization; of these, the buffering of plaque acids may predominate. Enhanced remineralization of white spot lesions may also be regarded as dynamic protective effects of saliva. Fluoride in saliva (from dentifrices, ingesta, etc.) may promote remineralization and (especially fluoride in plaque) inhibit demineralization. The design of experiments using caries models must take into account the static and dynamic effects of saliva. Some models admit a full expression of these effects, while others may exclude them, restricting the range of investigations possible. The possibility is raised that protective effects of saliva and therapeutic agents may act cooperatively.

scholarly journals The role of bound potassium ions in the hydrolysis of low concentrations of adenosine triphosphate by preparations of membrane fragments from ox brain cerebral cortex

1970 ◽  
Vol 120 (1) ◽  
pp. 15-24 ◽  
Author(s):  
P. S. G. Goldfarb ◽  
R. Rodnight
Keyword(s):  
Potassium Chloride ◽  
Magnesium Chloride ◽  
Adenosine Triphosphatase ◽  
Time Course ◽  
Atp Hydrolysis ◽  
Protein Ratio ◽  
Low Concentrations ◽  
Hydrolysis Of ◽  
Emission Flame

1. The intrinsic Na+, K+, Mg2+ and Ca2+ contents of a preparation of membrane fragments from ox brain were determined by emission flame photometry. 2. Centrifugal washing of the preparation with imidazole-buffered EDTA solutions decreased the bound Na+ from 90±20 to 24±12, the bound K+ from 27±3 to 7±2, the bound Mg2+ from 20±2 to 3±1 and the bound calcium from 8±1 to <1nmol/mg of protein. 3. The activities of the Na++K++Mg2+-stimulated adenosine triphosphatase and the Na+-dependent reaction forming bound phosphate were compared in the unwashed and washed preparations at an ATP concentration of 2.5μm (ATP/protein ratio 12.5pmol/μg). 4. The Na+-dependent hydrolysis of ATP as well as the plateau concentration of bound phosphate and the rate of dephosphorylation were decreased in the washed preparation. The time-course of formation and decline of bound phosphate was fully restored by the addition of 2.5μm-magnesium chloride and 2μm-potassium chloride. Addition of 2.5μm-magnesium chloride alone fully restored the plateau concentration of bound phosphate, but the rate of dephosphorylation was only slightly increased. Na+-dependent ATP hydrolysis was partly restored with 2.5μm-magnesium chloride; addition of K+ in the range 2–10μm-potassium chloride then further restored hydrolysis but not to the control rate. 5. Pretreatment of the washed preparation at 0°C with 0.5nmol of K+/mg of protein so that the final added K+ in the reaction mixture was 0.1μm restored the Na+-dependent hydrolysis of ATP and the time-course of the reaction forming bound phosphate. 6. The binding of [42K]potassium chloride by the washed membrane preparation was examined. Binding in a solution containing 10nmol of K+/mg of protein was linear over a period of 20min and was inhibited by Na+. Half-maximal inhibition of 42K+-binding required a 100-fold excess of sodium chloride. 7. It was concluded (a) that a significant fraction of the apparent Na+-dependent hydrolysis of ATP observed in the unwashed preparation is due to activation by bound K+ and Mg2+ of the Na++K++Mg2+-stimulated adenosine triphosphatase system and (b) that the enzyme system is able to bind K+ from a solution of 0.5μm-potassium chloride.

scholarly journals Role of Mammalian Auditory Cortex in the Perception of Elementary Sound Properties

2001 ◽  
Vol 85 (6) ◽  
pp. 2350-2358 ◽  
Author(s):  
Sanjiv K. Talwar ◽  
Pawel G. Musial ◽  
George L. Gerstein
Keyword(s):  
Auditory Cortex ◽  
Time Course ◽  
Auditory Evoked Potentials ◽  
Mammalian Species ◽  
Sound Intensity ◽  
Primary Auditory Cortex ◽  
Normal Hearing ◽  
Auditory Task ◽  
Experimental Conditions

Studies in several mammalian species have demonstrated that bilateral ablations of the auditory cortex have little effect on simple sound intensity and frequency-based behaviors. In the rat, for example, early experiments have shown that auditory ablations result in virtually no effect on the rat's ability to either detect tones or discriminate frequencies. Such lesion experiments, however, typically examine an animal's performance some time after recovery from ablation surgery. As such, they demonstrate that the cortex is not essential for simple auditory behaviors in the long run. Our study further explores the role of cortex in basic auditory perception by examining whether the cortex is normally involved in these behaviors. In these experiments we reversibly inactivated the rat primary auditory cortex (AI) using the GABA agonist muscimol, while the animals performed a simple auditory task. At the same time we monitored the rat's auditory activity by recording auditory evoked potentials (AEP) from the cortical surface. In contrast to lesion studies, the rapid time course of these experimental conditions preclude reorganization of the auditory system that might otherwise compensate for the loss of cortical processing. Soon after bilateral muscimol application to their AI region, our rats exhibited an acute and profound inability to detect tones. After a few hours this state was followed by a gradual recovery of normal hearing, first of tone detection and, much later, of the ability to discriminate frequencies. Surface muscimol application, at the same time, drastically altered the normal rat AEP. Some of the normal AEP components vanished nearly instantaneously to unveil an underlying waveform, whose size was related to the severity of accompanying behavioral deficits. These results strongly suggest that the cortex is directly involved in basic acoustic processing. Along with observations from accompanying multiunit experiments that related the AEP to AI neuronal activity, our results suggest that a critical amount of activity in the auditory cortex is necessary for normal hearing. It is likely that the involvement of the cortex in simple auditory perceptions has hitherto not been clearly understood because of underlying recovery processes that, in the long-term, safeguard fundamental auditory abilities after cortical injury.

scholarly journals Enhanced phosphorylation of Na+–Cl− co-transporter in experimental metabolic syndrome: role of insulin

2012 ◽  
Vol 123 (11) ◽  
pp. 635-647 ◽  
Author(s):  
Radko Komers ◽  
Shaunessy Rogers ◽  
Terry T. Oyama ◽  
Bei Xu ◽  
Chao-Ling Yang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Time Course ◽  
Kinase Inhibitor ◽  
Endogenous Expression ◽  
The Metabolic Syndrome ◽  
Mammalian Cell Lines ◽  
Phosphoinositide 3 Kinase

In the present study, we investigated the activity of the thiazide-sensitive NCC (Na+–Cl− co-transporter) in experimental metabolic syndrome and the role of insulin in NCC activation. Renal responses to the NCC inhibitor HCTZ (hydrochlorothiazide), as a measure of NCC activity in vivo, were studied in 12-week-old ZO (Zucker obese) rats, a model of the metabolic syndrome, and in ZL (Zucker lean) control animals, together with renal NCC expression and molecular markers of NCC activity, such as localization and phosphorylation. Effects of insulin were studied further in mammalian cell lines with inducible and endogenous expression of this molecule. ZO rats displayed marked hyperinsulinaemia, but no differences in plasma aldosterone, compared with ZL rats. In ZO rats, natriuretic and diuretic responses to NCC inhibition with HCTZ were enhanced compared with ZL rats, and were associated with a decrease in BP (blood pressure). ZO rats displayed enhanced Thr53 NCC phosphorylation and predominant membrane localization of both total and phosphorylated NCC, together with a different profile in expression of SPAK (Ste20-related proline/alanine-rich kinase) isoforms, and lower expression of WNK4. In vitro, insulin induced NCC phosphorylation, which was blocked by a PI3K (phosphoinositide 3-kinase) inhibitor. Insulin-induced reduction in WNK4 expression was also observed, but delayed compared with the time course of NCC phosphorylation. In summary, we report increased NCC activity in hyperinsulinaemic rodents in conjunction with the SPAK expression profile consistent with NCC activation and reduced WNK4, as well as an ability of insulin to induce NCC stimulatory phosphorylation in vitro. Together, these findings indicate that hyperinsulinaemia is an important driving force of NCC activity in the metabolic syndrome with possible consequences for BP regulation.

scholarly journals cAMP induces a rapid and reversible modification of the chemotactic receptor in Dictyostelium discoideum.

1985 ◽  
Vol 100 (3) ◽  
pp. 715-720 ◽  
Author(s):  
C Klein ◽  
J Lubs-Haukeness ◽  
S Simons
Keyword(s):  
Dictyostelium Discoideum ◽  
Concentration Dependence ◽  
Time Course ◽  
Camp Synthesis ◽  
Sds Page ◽  
Reversible Modification ◽  
Camp Receptor ◽  
Camp Stimulation ◽  
Stimulation Of

Stimulation, within 1 min after cAMP stimulation, of aggregation-competent Dictyostelium discoideum amebae was found to cause a rapid (within 1 min) modification of the cell's surface cAMP receptor. The modified receptor migrated on SDS PAGE as a 47,000-mol-wt protein, as opposed to a 45,000-mol-wt protein labeled on unstimulated cells. The length of time this modified receptor could be detected depended upon the strength of the cAMP stimulus: 3-4 min after treatment with 10(-7) M cAMP, cells no longer possessed the 47,000-mol-wt form of the cAMP receptor. Instead, the 45,000-mol-wt form was present. Stimulation of cells with 10(-5) M cAMP, however, resulted in the persistent (over 15 min) expression of the modified receptor. The time course, concentration dependence, and specificity of stimulus for this cAMP-induced shift in the cAMP receptor were found to parallel the cAMP-stimulated phosphorylation of a 47,000-mol-wt protein. In addition, both phenomena were shown to occur in the absence of endogenous cAMP synthesis. The possibility that the cAMP receptor is phosphorylated in response to cAMP stimulation, and the role of this event in cell desensitization, are discussed.

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