Date Thesis Awarded
Honors Thesis -- Access Restricted On-Campus Only
Bachelors of Science (BS)
Christopher A. Del Negro
John D. Griffin
Margaret Somosi Saha
Robin C. Looft-Wilson
We examined the neural bases of inspiratory bursts in the preBötzinger Complex (preBötC) in slice preparations of neonatal mice that retain respiratory network functions in vitro. It is well established that inward currents including persistent Na+ current (INaP) and Ca2+-activated nonspecific cation current (ICAN) initiate and maintain inspiratory bursts, but the ionic mechanisms of burst termination remain unknown. Since INaP and ICAN flux Na+, we hypothesized that activity-dependent processes coupled to Na+ accumulation may act to hyperpolarize the membrane and hasten or cause burst termination. We tested for the contribution of the Na+/K+ ATPase electrogenic pump current (Ipump), Na+-dependent K+ current (IK-Na), and ATP-dependent K+ current (IK-ATP). Pharmacological blockade of each of these three currents depolarized preBötC neurons and attenuated inspiratory bursts, which ultimately lead to a reversible cessation of respiratory motor output. In some cases the fictive respiratory rhythm transiently sped up before slowing down and then stopping altogether. We also estimated the post-burst hyperpolarization attributable to Ipump, IK-Na, and IK-ATP by simulating inspiratory bursts with current step commands in synaptically isolated preBötC neurons. Each current produced 3-8 mV transient hyperpolarization responses lasting 50-160 ms. We conclude that pharmacologically removing any of these activity-dependent outward currents induces a state of pathological depolarization that can extinguish spiking and thus inhibit further inspiratory burst activity. We posit that a substantial fraction of the preBötC enters this depolarized state, which prevents it from participating in rhythm generation and the respiratory motor output ceases. Activity-dependent (specifically Na+ dependent) outward currents appear to play a significant role in terminating inspiratory bursts, and should be integrated into cellular-level models of respiratory rhythm generation.
Krey, Rebecca, "Activity-dependent outward currents contribute to inspiratory burst termination in the preBötzinger Complex neurons of the neonatal mouse studied in vitro" (2010). Undergraduate Honors Theses. William & Mary. Paper 688.
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