Casey Diekman

• 
  Data Assimilation Methods for Conductance-Based Neuronal Modeling
  Casey Diekman
  Modern data assimilation (DA) techniques are widely used in climate science and weather prediction but have only recently begun to be applied in neuroscience. In this talk I will illustrate the use of DA algorithms to estimate unobserved variables and unknown parameters of conductance-based neuronal models and propose the bifurcation structure of inferred models as a qualitative measure of estimation success. I will then apply DA to electrophysiological recordings from suprachiasmatic nucleus neurons to develop models that provide insight into the functioning of the mammalian circadian clock. Finally, I will frame the selection of stimulus waveforms to inject into neurons during patch-clamp recordings as an optimal experimental design problem and present preliminary results on the optimal stimulus waveforms for improving the identifiability of parameters for a Hodgkin-Huxley-type model.
• 
  Eupnea, Tachypnea, and Autoresuscitation in a Closed-Loop Respiratory Control Model
  Casey Diekman

  The mechanisms underlying oscillations in a central pattern generator (CPG) may differ fundamentally in the intact organism versus an isolated CPG preparation. We investigate this aspect of rhythmogenesis in a computational model of closed-loop respiratory control, incorporating minimal models of the brainstem CPG, lung mechanics, oxygen handling, metabolism, and chemosensation. We analyze the model behavior using fast/slow dynamical systems analysis and open-loop/closed-loop control analysis. We show that eupnea-like bursting oscillations arise from a distinct mechanism in the intact (closed loop) versus isolated (open loop) systems. The closed-loop model exhibits bistability between eupnea-like bursting and tachypnea-like tonic spiking, and we demonstrate that imposed bouts of hypoxia can induce a dramatic transition from eupnea to tachypnea. For moderate bouts of hypoxia, the endogenous properties of the ionic conductances in the Butera-Rinzel-Smith CPG model can lead to spontaneous autoresuscitation and recovery to eupnea. We also find that chemosensory feedback gives the closed-loop control system greater robustness to changes in metabolic demand than the open-loop control system.