Year of Graduation
2022
Level of Access
Open Access Thesis
Embargo Period
5-19-2023
Department or Program
Neuroscience
First Advisor
Patsy Dickinson
Abstract
The crustacean heartbeat is produced and modulated by the cardiac ganglion (CG), a central pattern generator. In the American lobster, Homarus americanus, the CG consists of 4 small premotor cells (SCs) that electrically and chemically synapse onto 5 large motor cells (LCs). Rhythmic driver potentials in the SCs generate bursting in the LCs, which elicit downstream cardiac muscle contractions that are essential for physiological functions.
Endogenous neuromodulators mediate changes in the CG to meet homeostatic demands caused by environmental stressors. Nitric oxide (NO), a gaseous neuromodulator, inhibits the lobster CG. Heart contractions release NO, which directly decreases the CG burst frequency and indirectly decreases the heartbeat amplitude, to mediate negative feedback. I investigated NO’s inhibitory effects on the CG to further understand the mechanisms underlying intrinsic feedback.
Using extracellular recordings, I examined NO modulation of the SCs and LCs when coupled in the intact circuit and when firing independently in the ligatured preparation. Using two-electrode voltage clamp, I additionally analyzed the modulation of channel kinetics. Based on previous studies, I hypothesized that NO decreases the burst frequency of the LCs and SCs by modulating conductance properties of the voltage-gated A-type potassium current (IA). My data showed that NO decreased the burst frequency in the LCs and the burst duration in the SCs in a state-dependent manner. Furthermore, NO increased the IA inactivation time constant to decrease the LCs’ burst frequency. Thus, NO mediated inhibitory effects on cardiac output by differentially targeting both cell types and altering the IA current kinetics.