Differential Mechanisms Of Monoamine-Induced Oscillations In The Lobster Pyloric Pacemaker Neuron
Central pattern generator (CPG) is a specialized neuronal circuit that can produce rhythmic motor pattern in the absence of sensory or descending inputs that carry specific timing information. CPGs control basic rhythmic motor functions, such locomotion, respiration, mastication, peristalsis and others. The lobster pyloric circuit is a classical CPG, driven by a pacemaker neuron called the anterior burster (AB). In a synaptically isolated AB neuron, dopamine (DA) and serotonin (5HT) can each evoke rhythmic bursting, but appear to use different sets of currents to drive the burst (Harris-Warrick and Flamm, 1987). DA-induced bursting in the AB neuron is critically dependent on external calcium, minimally affected by external sodium concentration and insensitive to tetrodotoxin (TTX). In contrast, 5HT-induced bursting is critically dependent on the concentration of external sodium: low (50%) external sodium prevents bursting, and TTX abolishes bursting, while low external calcium only slows down the 5HT bursting without completely blocking it. I have tested the hypothesis that DA evokes oscillations by enhancing the calcium-activated non-selective current (I CAN ) , while 5HT induces oscillations by enhancing the persistent sodium current (I Na(P) ) . First, I have studied the properties of these slow inward currents in three different pyloric neurons: the anterior burster (AB) and two motor neurons: the pyloric dilator (PD) and the lateral pyloric (LP). Both currents exhibit cell-type specificity in their properties and modulation. The results of this project are presented in Chapter 2. In Chapters 3 and 4, I look at the functional significance of I CAN and I Na(P) in the pacemaker neuron AB in more detail. I have established that DA triggers the release of calcium ions from intracellular stores, which results in an activation of the calcium-activated non-selective current and rhythmic oscillations. It is particularly interesting that DA evokes AB bursting in part by modulating a conductance that has no intrinsic voltage dependence. Serotonin, on the other hand, inhibits two potassium outward currents, thereby uncovering the depolarizing effect of the persistent sodium current and generating bursting. Most likely, these two mechanisms are complementary in vivo and constitute a failproof system in regulating a vitally important physiological function. This system redundancy may represent a common design principle in biology.
Dissertation or Thesis