Dopamine Modulation of Two Subthreshold Currents Produces Phase Shifts in Activity of an Identified Motoneuron. Harris-Warrick, Ronald M., Lisa M. Coniglio, Robert M. Levini, Shay Gueron, and John Guckenheimer. Section of Neurobiology and Behavior, Seeley G. Mudd Hall, Cornell University, Ithaca, NY 14853, Mathematics Department and 4 Center for Applied Mathematics, 504 ETC Building, Cornell University, Ithaca, NY 14853, Department of Mathematics, Technion- Israel Institute of Technology, Haifa, Israel 32000.
APStracts 2:0191N, 1995.
SUMMARY AND CONCLUSIONS
1. The Lateral Pyloric (LP) neuron is a component of the 14-neuron pyloric central pattern generator in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus. In the pyloric rhythm, this neuron fires rhythmic bursts of action potentials whose phasing depends on the pattern of synaptic inhibition from other network neurons and on the intrinsic postinhibitory rebound properties of the LP cell itself. Bath-applied dopamine excites the LP cell and causes its activity to be phase-advanced in the pyloric motor pattern. At least part of this modulatory effect is due to dopaminergic modulation of the intrinsic rate of postinhibitory rebound in the LP cell. 2. The LP neuron was isolated from all detectable synaptic input. We measured the rate of recovery after 1 sec hyperpolarizing current injections of varying amplitudes, quantifying the latency to the first spike following the hyperpolarizing prepulse and the interval between the first and second action potentials. Dopamine reduced both the first spike latency and the first interspike interval (ISI) in the isolated LP neuron. During the hyperpolarizating presteps, the LP cell showed a slow depolarizing sag voltage that was enhanced by dopamine. 3. We used voltage clamp to analyze dopamine modulation of subthreshold ionic currents whose activity is affected by hyperpolarizing prepulses. Dopamine modulated the transient potassium current, IA, by reducing its maximal conductance and shifting its voltage dependence for activation and inactivation to more depolarized voltages. This outward current is normally transiently activated following hyperpolarization of the LP cell, and delays the rate of postinhibitory rebound; by reducing IA, dopamine thus accelerates the rate of rebound of the LP neuron. 4. Dopamine also modulated the hyperpolarization-activated inward current, Ih, by shifting its voltage dependence for activation 20 mV in the depolarizing direction and accelerating its rate of activation. This enhanced inward current helps accelerate the rate of rebound in the LP cell after inhibition. 5. The relative roles of Ih and IA in determining the first spike latency and first ISI were explored using pharmacological blockers of Ih (Cs+) and IA (4- aminopyridine, 4-AP). Blockade of Ih prolonged the first spike latency and first interspike interval, but only slightly reduced the net effect of dopamine. In the continued presence of Cs+, blockade of IA with 4-AP greatly shortened the first spike latency and first interspike interval. Under conditions where both Ih and IA were blocked, dopamine had no additional effect on the LP cell. 6. We used the dynamic clamp technique to further study the relative roles of IA and Ih modulation in dopamineÕs phase advance of the LP cell. We blocked the endogenous Ih with Cs+ and replaced it with a simulated current generated by a computer model of Ih. The neuron with simulated Ih gave curves relating the hyperpolarizing prepulse amplitude to first spike latency that were the same as in the untreated cell. Changing the computer parameters of the simulated Ih to those induced by dopamine without changing IA caused only a slight reduction in first spike latency, which was about 20% of the total reduction caused by dopamine in an untreated cell. Bath application of dopamine in the presence of Cs+ and simulated Ih (with control parameters) allowed us to determine the effect of altering IA but not Ih: this caused a significant reduction in first spike latency, but it was still only about 70% of the effect of dopamine in the untreated cell. Finally, in the continued presence of dopamine, changing the parameters of the simulated Ih to those observed with dopamine reduced the first spike latency to that seen with dopamine in the untreated cell. 7. We generated a mathematical model of the lobster LP neuron, based on the model of Buchholtz et al. (Buchholtz, et al. 1992) for the crab LP neuron. This model generated a similar curve of hyperpolarizing prepulse amplitude to first spike latency as that seen in normal LP neurons. Alteration of the parameters of IA and Ih to those observed in dopamine caused a significant reduction in first spike latency. Alteration of the Ih parameters alone had only a small effect, while alteration of the IA parameters alone had a much larger effect that was only slightly smaller than altering both currents together. 8. These results suggest that dopamine excites the LP neuron and phase advances its activity in the pyloric rhythm at least in part by modulating its intrinsic postinhibitory rebound properties. This modulation appears to be mediated by a reduction in IA and an enhancement of Ih. Quantitatively, the reduction of IA appears to be the major cause for the LP phase advance, while enhancement of Ih plays a more modest supporting role. We compare these conclusions with studies in other systems where the effects of IA and Ih on postinhibitory rebound have been analyzed. 

Received 29 March 1995; accepted in final form 15 June 1995.
APS Manuscript Number J206-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.