scholarly journals Synergy of AMPA and NMDA receptor currents in dopaminergic neurons: a modeling study

2015 ◽  
Author(s):  
Denis Zakharov ◽  
Lapis Christopher ◽  
Boris Gutkin ◽  
Alexey Kuznetsov

Dopaminergic (DA) neurons display two modes of firing: low-frequency tonic and high-frequency bursts. The high frequency firing within the bursts is attributed to NMDA, but not AMPA receptor activation. In our models of the DA neuron, both biophysical and abstract, the NMDA receptor current can significantly increase their firing frequency, whereas the AMPA receptor current is not able to evoke high-frequency activity and usually suppresses firing. However, both currents are produced by glutamate receptors and, consequently, are often co-activated. Here we consider combined influence of AMPA and NMDA synaptic input in the models of the DA neuron. Different types of neuronal activity (resting state, low frequency, or high frequency firing) are observed depending on the conductance of the AMPAR and NMDAR currents. In two models, biophysical and reduced, we show that the firing frequency increases more effectively if both receptors are co-activated for certain parameter values. In particular, in the more quantitative biophysical model, the maximal frequency is 40% greater than that with NMDAR alone. The dynamical mechanism of such frequency growth is explained in the framework of phase space evolution using the reduced model. In short, both the AMPAR and NMDAR currents flatten the voltage nullcline, providing the frequency increase, whereas only NMDA prevents complete unfolding of the nullcline, providing robust firing. Thus, we confirm a major role of the NMDAR in generating high-frequency firing and conclude that AMPAR activation further significantly increases the frequency.

2019 ◽  
Vol 85 (1(I)) ◽  
pp. 64-71 ◽  
Author(s):  
M. M. Gadenin

The cycle configuration at two-frequency loading regimes depends on the number of parameters including the absolute values of the frequencies and amplitudes of the low-frequency and high-frequency loads added during this mode, the ratio of their frequencies and amplitudes, as well as the phase shift between these harmonic components, the latter having a significant effect only with a small ratio of frequencies. Presence of such two-frequency regimes or service loading conditions for parts of machines and structures schematized by them can significantly reduce their endurance. Using the results of experimental studies of changes in the endurance of a two-frequency loading of specimens of cyclically stable, cyclically softened and cyclically hardened steels under rigid conditions we have shown that decrease in the endurance under the aforementioned conditions depends on the ratio of frequencies and amplitudes of operation low-frequency low-cycle and high-frequency vibration stresses, and, moreover, the higher the level of the ratios of amplitudes and frequencies of those stacked harmonic processes of loading the greater the effect. It is shown that estimation of such a decrease in the endurance compared to a single frequency loading equal in the total stress (strains) amplitudes can be carried out using an exponential expression coupling those endurances through a parameter (reduction factor) containing the ratio of frequencies and amplitudes of operation cyclic loads and characteristic of the material. The reduction is illustrated by a set of calculation-experimental curves on the corresponding diagrams for each of the considered types of materials and compared with the experimental data.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Reuben Howden ◽  
Eva Gougian ◽  
Marcus Lawrence ◽  
Samantha Cividanes ◽  
Wesley Gladwell ◽  
...  

Nrf2protects the lung from adverse responses to oxidants, including 100% oxygen (hyperoxia) and airborne pollutants like particulate matter (PM) exposure, but the role ofNrf2on heart rate (HR) and heart rate variability (HRV) responses is not known. We hypothesized that genetic disruption ofNrf2would exacerbate murine HR and HRV responses to severe hyperoxia or moderate PM exposures.Nrf2-/-andNrf2+/+mice were instrumented for continuous ECG recording to calculate HR and HRV (low frequency (LF), high frequency (HF), and total power (TP)). Mice were then either exposed to hyperoxia for up to 72 hrs or aspirated with ultrafine PM (UF-PM). Compared to respective controls, UF-PM induced significantly greater effects on HR (P<0.001) and HF HRV (P<0.001) inNrf2-/-mice compared toNrf2+/+mice.Nrf2-/-mice tolerated hyperoxia significantly less thanNrf2+/+mice (~22 hrs;P<0.001). Reductions in HR, LF, HF, and TP HRV were also significantly greater inNrf2-/-compared toNrf2+/+mice (P<0.01). Results demonstrate thatNrf2deletion increases susceptibility to change in HR and HRV responses to environmental stressors and suggest potential therapeutic strategies to prevent cardiovascular alterations.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Xin Zhang ◽  
Bin Cheng ◽  
Xianghong Jing ◽  
Yongfa Qiao ◽  
Xinyan Gao ◽  
...  

A large number of studies have been conducted to explore the efficacy of electroacupuncture (EA) for the treatment of gastrointestinal motility. While several lines of evidence addressed the basic mechanism of EA on gastrointestinal motility regarding effects of limb and abdomen points, the mechanism for effects of the back points on gastric motility still remains unclear. Here we report that the NMDA receptor (NMDAR) antagonist kynurenic acid inhibited the gastric emptying increase induced by high-intensity EA at BL21 and agonist NMDA enhanced the effect of the same treatment. EA at BL21 enhanced NMDAR, but not AMPA receptor (AMPAR) component of miniature excitatory postsynaptic current (mEPSC) in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). In sum, our data demonstrate an important role of NMDAR-mediated synaptic transmission of gastric-projecting DMV neurons in mediating EA at BL21-induced enhancement of gastric emptying.


2018 ◽  
Vol 10 (2) ◽  
pp. 235
Author(s):  
Fitria Mustika ◽  
Tengku Muhammad Sahudra

This study aims to determine the role of the family, community, and tertiary environment towards the formation of caring character in the geography education student environment. The output of this study was a four-indexed indexed education journal and a UNIMED google scolar. Samples from the study population were 20 respondents with 30 items about questionnaires. The time of the study starts from May 2018 to October 2018. The measurement scale in this study is the scale of the briquette. Data collection by means of library studies, interviews, questionnaires, and documentation. This research was conducted by distributing questionnaire questionnaires and interviews. Based on the results of questionnaire data processing, the family environment has a very high frequency in the formation of character of the student's environmental care with an achievement level of a total score of 91%. Furthermore, the role of the campus environment also has a high frequency in the formation of the character of the student's environmental care with a total score of 89%. Whereas the family environment has a low frequency in the formation of character of student environmental care with a total score of 57%. It can be concluded that the family environment has the most role in forming the character of the student's environmental care.


1981 ◽  
Vol 51 (2) ◽  
pp. 317-320 ◽  
Author(s):  
S. R. Garfin ◽  
C. M. Tipton ◽  
S. J. Mubarak ◽  
S. L. Woo ◽  
A. R. Hargens ◽  
...  

The effect of fasciotomy on muscle tension (measured by a force transducer attached to the tendon) and interstitial fluid pressure (measured by Wick catheters in the muscle belly) was studied in the anterolateral compartments of 13 dog hindlimbs. Muscle tension and pressure were monitored in the tibialis cranialis muscle after low- and high-frequency stimulation of the peroneal nerve to produce twitch- and tetanic-type contractions. Fasciotomy decreased muscle force during the low-frequency stimulation by 16% (35.3 +/- 4.9 to 28.4 +/- 3.9 N) and during the high-frequency stimulation by 10% (60.8 %/- 4.9 to 54.8 +/- 3.9 N). Muscle pressure decreased 50% after fasciotomy under both conditions, 15 +/- 2 to 6 +/- 1 mmHg and 84 +/- 17 to 41 +/- 8 mmHg), respectively. Repeated functional evaluations during the testing procedure indicated that muscle fatigue was not a major factor in these results. It was concluded that fascia is important in the development of muscle tension and changes in interstitial pressure. Furthermore, the results raised questions concerning the merits of performing a fasciotomy for athletes with a compartment syndrome.


1971 ◽  
Vol 29 (3) ◽  
pp. 768-770 ◽  
Author(s):  
G. McA. Kimbrell ◽  
D. Chesler

To clarify the relationship between dominance status and frequency of specific sub-classes of agonistic behavior in response to foot shock, 30 mice were selected on the basis of high- or low-dominance status and paired in a foot-shock situation. Dominant pairs exhibit a high frequency of defensive behavior patterns whereas submissive pairs exhibit a very low frequency of defensive patterns.


2006 ◽  
Vol 95 (2) ◽  
pp. 932-947 ◽  
Author(s):  
Alexey S. Kuznetsov ◽  
Nancy J. Kopell ◽  
Charles J. Wilson

Dopaminergic neurons of the midbrain fire spontaneously at rates <10/s and ordinarily will not exceed this range even when driven with somatic current injection. When driven at higher rates, these cells undergo spike failure through depolarization block. During spontaneous bursting of dopaminergic neurons in vivo, bursts related to reward expectation in behaving animals, and bursts generated by dendritic application of N-methyl-d-aspartate (NMDA) agonists, transient firing attains rates well above this range. We suggest a way such high-frequency firing may occur in response to dendritic NMDA receptor activation. We have extended the coupled oscillator model of the dopaminergic neuron, which represents the soma and dendrites as electrically coupled compartments with different natural spiking frequencies, by addition of dendritic AMPA (voltage-independent) or NMDA (voltage-dependent) synaptic conductance. Both soma and dendrites contain a simplified version of the calcium-potassium mechanism known to be the mechanism for slow spontaneous oscillation and background firing in dopaminergic cells. The compartments differ only in diameter, and this difference is responsible for the difference in natural frequencies. We show that because of its voltage dependence, NMDA receptor activation acts to amplify the effect on the soma of the high-frequency oscillation of the dendrites, which is normally too weak to exert a large influence on the overall oscillation frequency of the neuron. During the high-frequency oscillations that result, sodium inactivation in the soma is removed rapidly after each action potential by the hyperpolarizing influence of the dendritic calcium-dependent potassium current, preventing depolarization block of the spike mechanism, and allowing high-frequency spiking.


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