Modeling Subfornical Organ Neurons
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Subfornical organ (SFO) neurons exhibit heterogeneity in ionic current expression and spiking behaviour, where the two major phenotypes appear as tonic and burst firing. Insight into the mechanisms behind this heterogeneity is critical for understanding how the SFO, a sensory circumventricular organ, integrates and selectively influences autonomic nervous system, endocrine, and behavioural function. To integrate efficient methods for investigating this heterogeneity, we built a single-compartment, Hodgkin-Huxley type model of an SFO neuron that is parameterized by SFO-specific in vitro voltage-clamp data. The model accounts for the individual membrane potential distribution and spike train variability of tonic and burst firing SFO neurons. Analysis of model dynamics confirms that a persistent Na+ and a Ca2+ current are required for burst initiation and maintenance, and suggests that a slow-activating K+ current may be responsible for burst termination in SFO neurons. Additionally, the model suggests that heterogeneity in current expression and subsequent influence on spike afterpotential underlies the behavioural differences between tonic and burst firing SFO neurons. The use of our model in coordination with in vitro electrophysiology experiments, provides a platform for explaining and predicting the response of SFO neurons to various combinations of circulating signals, as demonstrated by our preliminary investigation of inflammatory and cardiovascular signal integration. Our model predicts that 24-hr incubation in tumor necrosis factor alpha, an inflammatory cytokine, will result in the potentiation of SFO neuron excitability in response to angiotensin II. This prediction provides a potential mechanism to support previous findings that inflammation may be potentiating angiotensin II actions in the SFO. Future studies will work to further elucidate the mechanisms underlying the integration of physiologically important signals in the SFO.