Modeling A-current Modulation in Tritonia diomedea

• Main Author: Darghouth, Naim Richard
• Format: Others
• Language: en_US
• Published: Georgia Institute of Technology 2005
• Subjects: Neuronal modeling; Neuromodulation
• Online Access: http://hdl.handle.net/1853/7257

This study uses a conductance-based computer simulation to test the feasibility of a mechanism underlying a newly-described dynamic form of neuromodulation, called spike-timing dependent neuromodulation (STDN). In the mollusc, Tritonia diomedea, it was recently found that a serotonergic neuron (called DSI) alters the synaptic strength of another neuron (VSI-B) in a temporally biphasic-bidirectional manner, with an initial potentiation followed by prolonged synaptic depression (Sakurai and Katz 2003). Physiological evidence suggested that the depression phase is due to serotonin enhancing the A-current in VSI-B, thereby causing spike-narrowing or a decrease in spike amplitude, and thus a decrease in transmitter release. We sought to test the feasibility of this mechanism by developing a conductance-based model of VSI-B using a Hodgkin-Huxley style simulation with a minimal number of ion conductances: A-current, delayed rectifier potassium, fast sodium, and leak channels. From our model, we conducted simulations in order to study how the spike shape of the VSI-B action potential changes as the A-current conductance is enhanced, from which we are able to predict the amount of depression in the post-synaptic cell. Our model indicates that the depression due to the narrowing of the spike with A-current enhancement is sufficient to account for the empirically observed depression during STDN, although it suggests a greater effect of serotonin at the terminals than is observed in the soma. Additionally, the model suggested that the slow inactivation kinetics of the A-current cannot explain the dynamics of the depression phase of STDN. These modeling results suggest that serotonergic modulation of the A-current plays a role in STDN but does not account for its dynamics.