Dopamine modulation of transient potassium current evokes phase shifts in a central pattern generator network

Abstract

Bath application of dopamine modifies the rhythmic motor pattern generated by the 14 neuron pyloric network in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus. Among other effects, dopamine excites many of the pyloric constrictor (PY) neurons to fire at high frequency and phase-advances the timing of their activity in the motor pattern. These responses arise in part from direct actions of dopamine to modulate the intrinsic electrophysiological properties of the PY cells, and can be studied in synaptically isolated neurons. The rate of rebound following a hyperpolarizing prestep and the spike frequency during a subsequent depolarization are both accelerated by dopamine. Based on theoretical simulations, Hartline (1979) suggested that the rate of postinhibitory rebound in stomatogastric neurons could vary with the amount of voltage- sensitive transient potassium current (IA). Consistent with this prediction, we found that dopamine evokes a net conductance decrease in synaptically isolated PY neurons. In voltage clamp, dopamine reduces IA, specifically by reducing the amplitude of the slowly inactivating component of the current and shifting its voltage activation curve in the depolarized direction. 4-Aminopyridine, a selective blocker of IA in stomatogastric neurons, mimics and occludes the effects of dopamine on isolated PY neurons. A conductance-based mathematical model of the PY neuron shows appropriate changes in activity upon quantitative modification of the IA parameters affected by dopamine. These results demonstrate that dopamine excites and phase-advances the PY neurons in the rhythmic pyloric motor pattern at least in part by reducing the transient K+ current, IA.

Monoamine Control of the Pacemaker Kernel and Cycle Frequency in the Lobster Pyloric Network

“…In the presence of DA, it appears that the synaptic input to the AB-PD pacemaker kernel from the LP and VD neurons plays no significant role in determining the final DA-induced cycle frequency. This is despite the fact that DA strongly excites the LP neuron (Flamm and HarrisWarrick, 1986b;Harris-Warrick et al, 1995a) and enhances LP inhibition of the PD neurons (Johnson et al, 1995). The quantitative effect of DA on LP activity provides an explanation for this result.…”

Strategies for delineating spinal locomotor rhythm-generating networks and the possible role of Hb9 interneurones in rhythmogenesis

“…Furthermore, application of the neuromodulator dopamine to the intact network leads to an increase in cycle frequency through variable mechanisms in different cell types (Harris-Warrick et al, 1998). In the pyloric constrictor (PY) cells, for example, dopamine decreases the delay to onset of firing and increases firing frequency, effects mediated by a reduction in I A (Harris-Warrick et al, 1995a). Taken together, these studies have beautifully demonstrated the dynamic interaction of intrinsic properties and network activity, and the harmonisation of the control of these properties and the network by neuromodulators.…”

Arthropod D2 receptors positively couple with cAMP through the Gi/o protein family

“…A wealth of information exists on the monoaminergic modulation of ion currents and neuronal firing properties (Flamm and Harris-Warrick, 1986;HarrisWarrick et al, 1995b;Harris-Warrick et al, 1995a;Harris-Warrick et al, 1998;Kloppenburg et al, 1999;Johnson et al, 2003), but nothing is known about the transduction cascades mediating these effects. To extend the usefulness of this model system and gain insight into how component neurons integrate biochemical and electrical processes, we have begun a molecular characterization of DARs in this central pattern generator (CPG).…”