A computational model of TIDA neuron oscillations

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Tuberoinfundibular dopaminergic (TIDA) neurons in the hypothalamus inhibit prolactin release from the pituitary by secreting dopamine into the portal vessels of the median eminence. In whole cell recordings in male rat slices TIDA neurons show a spontaneous, slow oscillation, which has a strong autocoherence. The oscillation is phase locked across neurons and this phase locking is believed to be mediated by gap junction coupling between TIDA neurons. Here we use computational models to investigate how the ion channels of the TIDA neuron give rise the oscillation typical for these neurons and how gap junctions influence this oscillation. Using a biophysically detailed model we tested the hypothesis that the currents Ileak, Ih, INa,t, INa, p, IK,delayed rectifier, IK,A, IBK and ICa,L would be sufficient to produce the TIDA oscillation. This model showed a spontaneous oscillation that displays several features of the TIDA oscillation. However, compared to the in vitro results, the transition to the UP state and the transition to the DOWN state were too abrupt in this model. The maximum conductance strength of the slowly activating currents could be varied in a certain range, preserving the oscillation, INa, p and ICa,L are more sensitive to changes than IBK and Ih. Spiking was not necessary to make the model oscillate, although the deletion of spiking changed the oscillation frequency and maximum voltage. Furthermore, we show a simple oscillating model of the rat TIDA neuron, including gap junction coupling. We found that the modeled neurons phase lock for CC > 5% and that CCs up to 47% can slow down the oscillation in the modeled neuron. We conclude that a model using the hypothesized combination of currents captures many features of the TIDA oscillation and that gap junctions may be important to slow down the oscillation and hyperpolarize the nadir.
Faculteit der Sociale Wetenschappen