Dopamine Activates Two Different Receptors to Produce Variability in Sign at an Identified Synapse

Abstract

Dopamine activates two different receptors to produce variability in sign at an identified synapse. Chemical synaptic transmission was investigated at a central synapse between identified neurons in the freshwater snail, Lymnaea stagnalis. The presynaptic neuron was the dopaminergic cell, Right Pedal Dorsal one (RPeD1). The postsynaptic neuron was Visceral Dorsal four (VD4). These neurons are components of the respiratory central pattern generator. The synapse from RPeD1 to VD4 showed variability of sign, i.e., it was either inhibitory (monophasic and hyperpolarizing), biphasic (depolarizing followed by hyperpolarizing phases), or undetectable. Both the inhibitory and biphasic synapse were eliminated by low Ca2+/high Mg2+ saline and maintained in high Ca2+/high Mg2+ saline, indicating that these two types of connections were chemical and monosynaptic. The latency of the inhibitory postsynaptic potential (IPSP) in high Ca2+/high Mg2+ saline was ∼43 ms, whereas the biphasic postsynaptic potential (BPSP) had ∼12-ms latency in either normal or high Ca2+/high Mg2+ saline. For a given preparation, when dopamine was pressured applied to the soma of VD4, it always elicited the same response as the synaptic input from RPeD1. Thus, for a VD4 neuron receiving an IPSP from RPeD1, pressure application of dopamine to the soma of VD4 produced an inhibitory response similar to the IPSP. The reversal potentials of the IPSP and the inhibitory dopamine response were both approximately −90 mV. For a VD4 neuron with a biphasic input from RPeD1, pressure-applied dopamine produced a biphasic response similar to the BPSP. The reversal potentials of the depolarizing phase of the BPSP and the biphasic dopamine response were both approximately −44 mV, whereas the reversal potentials for the hyperpolarizing phases were both approximately −90 mV. The hyperpolarizing but not the depolarizing phase of the BPSP and the biphasic dopamine response was blocked by the d-2 dopaminergic antagonist (±) sulpiride. Previously, our laboratory demonstrated that both IPSP and the inhibitory dopamine response are blocked by (±) sulpiride. Conversely, the depolarizing phase of both the BPSP and the biphasic dopamine response was blocked by the Cl− channel antagonist picrotoxin. Finally, both phases of the BPSP and the biphasic dopamine response were desensitized by continuous bath application of dopamine. These results indicate that the biphasic RPeD1 → VD4 synapse is dopaminergic. Collectively, these data suggest that the variability in sign (inhibitory vs. biphasic) at the RPeD1 → VD4 synapse is due to activation of two different dopamine receptors on the postsynaptic neuron VD4. This demonstrates that two populations of receptors can produce two different forms of transmission, i.e., the inhibitory and biphasic forms of the single RPeD1 → VD4 synapse.