Computer Modeling of D, L – Homocysteic Acid Microinjection into the Bötzinger Complex Area

The impact of D,L – homocysteic acid (DLH) microinjection (non-specific glutamate receptor agonist that causes excitation of neurons) into the Bötzinger complex area (BOT) was simulated using computer model of quiet breathing and cough reflex. Integrated signals from simulated neuronal populations innervating inspiratory phrenic and expiratory lumbar motoneurons were obtained. We analysed durations and amplitudes of these “pre-phrenic and pre-lumbar” activities during quiet breathing and cough reflex and the number of coughs elicited by a fictive 10-second-long stimulation. Model fibre population provides virtual DLH related excitation to expiratory neuronal populations with augmenting discharge pattern (BOT neurons). The excitation was modelled by a higher number of fibres and terminals (simulated a higher number of excitatory inputs) or by a higher synaptic strength (simulated a higher effect of excitatory inputs).

Our simulations have demonstrated a high analogy of cough and breathing changes to those observed in animal experiments. The simulated neuronal excitations in the BOT led to cough depression represented by a lower cough number and a cough neuronal activity of the lumbar nerve. Despite the shortening of the phrenic activity during cough (compared to quiet breathing), which was not observed in animal experiments, our simulations confirm the ability of the computer model to simulate motor processes in the respiratory system. The computer model of functional respiratory / cough neural network is capable to confirm and / or predict the results obtained on animals.