New Mechanism Of Aortic Baroreceptor Encoding Blood Pressure Signal

How blood pressures are encoded by baroreceptors is of fundamental importance in neuroscience. Baroreceptors are stretch-sensitive neural terminals which response to static and dynamic arterial blood pressure variations by evoking action potentials at the connected nerve fibers. It is well established in neurophysiology that baroreceptors and their sensory nerves represent the level of blood pressure by means of action potential frequency. The intensity of external signal is believed encoded in the mean frequency of firing trains, and the frequency of impulse is positively correlated to external stimulus density. Since the size of baroreceptor terminals are very small, it is still difficult to directly observe the relation between receptor potential and firing frequency on the nerve fibers. Combining techniques from neuroscience, nonlinear dynamics, information and computer science, it is possible to study the coding mechanisms of barorceptors. In the present study, we investigated the firing pattern and pattern transition (bifurcation) regularities by single unit recording on depression nerves in rat and rabbit. We formulated a mathematical model of barorecepotr and simulated the coding processes. The results provided a basis for a deeper understanding of complex and variable firing rhythm, identification of the relationship between dynamic firing rhythm and dynamic external signal. The dynamic coding processes were emphasized in the research and discussion. The study also gives a new viewpoint and method to theoretically study the neural firing rhythm and neural coding mechanism.In the present study, using methods of nonlinear dynamics as well as physiological experiments, the biophysical mechanism and physiological significance of the encoding of blood pressure by aortic arch baroreceptor was studied. The aortic arch baroreceptor from both rats and rabbits were chosen as experimental models. The neural firing and aortic blood pressure were recorded simultaneously. The biological relevant theoretical model was formed by considering transformation of blood vessel, generation of receptor potential, initiation of action potential. The theoretical model was analyzed theoretically, and the experimental results were compared with the numeric simulation. The theoretical analysis could reproduce the present experimental results and was used to guide future experiment. On the other hand, the experimental results verified the theoretical analysis.The main results are as follows.1, In experiments, we observed that the firing pattern changed with dynamic variation. When the average level of blood pressure was increased from a relatively lower level, the firing pattern of depression fibers changed from resting, to firing within systolic period, to continuous firing, to firing within diastolic period, and finally to resting caused by depolarization block at a relatively high blood pressure level. Five different firing patterns were identified, including three firing states and two resting states. The "paradoxical firing pattern" observed at high ranged of blood pressure was explained by mechanism of "depolarization block".2, We formulated an realistic mathematical model based on the transduction process. Multiple compartments were employed to represent blood vessel, receptor region, and the coding region to, respectively, simulate the transformation, receptor potential generation, and action potential initiation. By adjusting the same parameters as used in experiments, the experimental results were reproduced successfully.3, The simulation revealed mechanisms underpinning firing patterns transition. When the static blood pressure was increased, the deterministic form of the formulated model exhibited transition from polarized resting, to tonic firing, and to depolarized resting behaviors. With consideration of biological fluctuation, the stochastic form of the model exhibited resting, on-off firing, tonic firing, integer multiple firing, and depolarized resting.Under driven of dynamic blood pressure, the stochastic model generated resting, firing within systolic period, tonic firing, firing within diastolic period, and depolarized resting with respect to increase of blood pressure. The process reproduced the experiment successfully.4. In analysis of the mathematical mode, it was revealed that increase of static pressure induced subcritical Hopf bifurcation and caused firing, induced supercritical Hopf bifurcation and caused transition from firing to depolarized resting. The on-off and integer multiple firing were induced by dynamic noise at the bifurcation points, and the bifurcation from firing state to depolarized resting generated "paradoxical firing". This mechanism also explains the firing appeared within the diastolic period and the resting within the systolic period.This new finding implies the existence of working range for single baroreceptors as well as the possibility of population encoding of blood pressure information by all baroreceptors as a whole. In the cases of other sensations like audition, the working range of single receptors is limited and the complete sensory range is formed by the collaboration in receptor populations. Our results imply that baroreceptors may also have to'collaborate' under certain blood pressure to encode the information of blood pressure. The validity of this implication should be further investigateThe above results indicate that blood pressure dynamically modulates the barareceptor to experience transition on the basis of the bifurcation structure of the model, and the structure is readily produced with the deterministic model by using static blood pressure as the bifurcation parameter. In the case of dynamic changes of blood pressure, the receptor system is driven to evolve on the bifurcation and thus generates divers firing patterns, including the "paradoxical firing".With help of nonlinear dynamics of bifurcation theories, the encoding of blood pressure changes by baroreceptors can be deeply revealed. The mechanism explains relationships between dynamic properties of blood pressure and temporal rhythms of the firing trains on single depression nerve fibers, including firing pattern dynamic and firing frequency. Further investigations may formulate quantitative theories for encoding by the baroreceptors.