62 research outputs found
Modeling the differentiation of A- and C-type baroreceptor firing patterns
The baroreceptor neurons serve as the primary transducers of blood pressure
for the autonomic nervous system and are thus critical in enabling the body to
respond effectively to changes in blood pressure. These neurons can be
separated into two types (A and C) based on the myelination of their axons and
their distinct firing patterns elicited in response to specific pressure
stimuli. This study has developed a comprehensive model of the afferent
baroreceptor discharge built on physiological knowledge of arterial wall
mechanics, firing rate responses to controlled pressure stimuli, and ion
channel dynamics within the baroreceptor neurons. With this model, we were able
to predict firing rates observed in previously published experiments in both A-
and C-type neurons. These results were obtained by adjusting model parameters
determining the maximal ion-channel conductances. The observed variation in the
model parameters are hypothesized to correspond to physiological differences
between A- and C-type neurons. In agreement with published experimental
observations, our simulations suggest that a twofold lower potassium
conductance in C-type neurons is responsible for the observed sustained basal
firing, whereas a tenfold higher mechanosensitive conductance is responsible
for the greater firing rate observed in A-type neurons. A better understanding
of the difference between the two neuron types can potentially be used to gain
more insight into the underlying pathophysiology facilitating development of
targeted interventions improving baroreflex function in diseased individuals,
e.g. in patients with autonomic failure, a syndrome that is difficult to
diagnose in terms of its pathophysiology.Comment: Keywords: Baroreflex model, mechanosensitivity, A- and C-type
afferent baroreceptors, biophysical model, computational mode
Systemic virus distribution and host responses in brain and intestine of chickens infected with low pathogenic or high pathogenic avian influenza virus
<p>Abstract</p> <p>Background</p> <p>Avian influenza virus (AIV) is classified into two pathotypes, low pathogenic (LP) and high pathogenic (HP), based on virulence in chickens.</p> <p>Differences in pathogenicity between HPAIV and LPAIV might eventually be related to specific characteristics of strains, tissue tropism and host responses.</p> <p>Methods</p> <p>To study differences in disease development between HPAIV and LPAIV, we examined the first appearance and eventual load of viral RNA in multiple organs as well as host responses in brain and intestine of chickens infected with two closely related H7N1 HPAIV or LPAIV strains.</p> <p>Results</p> <p>Both H7N1 HPAIV and LPAIV spread systemically in chickens after a combined intranasal/intratracheal inoculation. In brain, large differences in viral RNA load and host gene expression were found between H7N1 HPAIV and LPAIV infected chickens. Chicken embryo brain cell culture studies revealed that both HPAIV and LPAIV could infect cultivated embryonic brain cells, but in accordance with the absence of the necessary proteases, replication of LPAIV was limited. Furthermore, TUNEL assay indicated apoptosis in brain of HPAIV infected chickens only. In intestine, where endoproteases that cleave HA of LPAIV are available, we found minimal differences in the amount of viral RNA and a large overlap in the transcriptional responses between HPAIV and LPAIV infected chickens. Interestingly, brain and ileum differed clearly in the cellular pathways that were regulated upon an AI infection.</p> <p>Conclusions</p> <p>Although both H7N1 HPAIV and LPAIV RNA was detected in a broad range of tissues beyond the respiratory and gastrointestinal tract, our observations indicate that differences in pathogenicity and mortality between HPAIV and LPAIV could originate from differences in virus replication and the resulting host responses in vital organs like the brain.</p
Modeling the Afferent Dynamics of the Baroreflex Control System
In this study we develop a modeling framework for predicting baroreceptor firing rate as a function of blood pressure. We test models within this framework both quantitatively and qualitatively using data from rats. The models describe three components: arterial wall deformation, stimulation of mechanoreceptors located in the BR nerve-endings, and modulation of the action potential frequency. The three sub-systems are modeled individually following well-established biological principles. The first submodel, predicting arterial wall deformation, uses blood pressure as an input and outputs circumferential strain. The mechanoreceptor stimulation model, uses circumferential strain as an input, predicting receptor deformation as an output. Finally, the neural model takes receptor deformation as an input predicting the BR firing rate as an output. Our results show that nonlinear dependence of firing rate on pressure can be accounted for by taking into account the nonlinear elastic properties of the artery wall. This was observed when testing the models using multiple experiments with a single set of parameters. We find that to model the response to a square pressure stimulus, giving rise to post-excitatory depression, it is necessary to include an integrate-and-fire model, which allows the firing rate to cease when the stimulus falls below a given threshold. We show that our modeling framework in combination with sensitivity analysis and parameter estimation can be used to test and compare models. Finally, we demonstrate that our preferred model can exhibit all known dynamics and that it is advantageous to combine qualitative and quantitative analysis methods
Meteorological analysis : fifth progress report.
http://deepblue.lib.umich.edu/bitstream/2027.42/3588/5/bac4618.0005.001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/3588/4/bac4618.0005.001.tx
Meteorological analysis : fourth progress report.
http://deepblue.lib.umich.edu/bitstream/2027.42/3587/5/bac4618.0004.001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/3587/4/bac4618.0004.001.tx
Meteorological analysis : final report.
http://deepblue.lib.umich.edu/bitstream/2027.42/3589/5/bac4618.0006.001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/3589/4/bac4618.0006.001.tx
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