title: Dopamine modulation of two subthreshold currents produces phase shifts in activity of an identified motoneuron.
abstract: 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-s 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 pre-steps, 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 after 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 ISI, 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 ISI. 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 dopamine's 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 approximately 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 approximately 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. for the crab LP neuron.
authors.affiliation: Section of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Harris-Warrick
authors.forename: L M
authors.initials: LM
authors.lastname: Coniglio
authors.forename: R M
authors.initials: RM
authors.lastname: Levini
authors.forename: S
authors.initials: S
authors.lastname: Gueron
authors.forename: J
authors.initials: J
authors.lastname: Guckenheimer
mesh_terms: D000818:Animals; D004056:Differential Threshold; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D004553:Electric Conductivity; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000502:physiology; D008959:Models, Neurological; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D008121:Nephropidae; D009433:Neural Inhibition; D018408:Patch-Clamp Techniques; D010507:Periodicity; D011188:Potassium / Q000502:physiology; D011708:Pylorus / Q000294:innervation / Q000502:physiology; D013569:Synapses / Q000502:physiology
chemical_list: D011188:Potassium; D004298:Dopamine