Multiple neuromodulators continuously act in concert to shape the properties of neural circuits. Different neurmodulators can activate distinct receptors but have overlapping signaling pathways or targets through co-modulation. Mechanisms underlying circuit output and its functional consequences, therefore, depend on how neuromodulators interact on these shared targets, a process that is poorly understood. We explored the quantitative rules of co-modulation of two principal targets of neuromodulation, voltage-gated ionic currents and synaptic currents, in the pyloric circuit of the stomatogastric ganglion (STG) of the crab, Cancer borealis. The neuropeptides proctolin (Proc) and CCAP modulate STG synapses and c... More
Multiple neuromodulators continuously act in concert to shape the properties of neural circuits. Different neurmodulators can activate distinct receptors but have overlapping signaling pathways or targets through co-modulation. Mechanisms underlying circuit output and its functional consequences, therefore, depend on how neuromodulators interact on these shared targets, a process that is poorly understood. We explored the quantitative rules of co-modulation of two principal targets of neuromodulation, voltage-gated ionic currents and synaptic currents, in the pyloric circuit of the stomatogastric ganglion (STG) of the crab, Cancer borealis. The neuropeptides proctolin (Proc) and CCAP modulate STG synapses and converge to activate the voltage-gated ionic current IMI in multiple STG neurons. Using simultaneous voltage-clamp recordings from the reciprocally connected pyloric neurons PD and LP, we examined the validity of a simple dose-dependent quantitative rule that co-modulation by Proc and CCAP can be predicted as the linear sum of the individual effects of each modulator, up to saturation. We found that this rule is valid for the co-modulation of the synapses between these two neurons, but not for the activation of IMI, where co-modulation was found to be sublinear. Given the high level of evolutionary conservation of neuromodulator receptors and signaling pathways, such distinct rules for co-modulation of different components within the same neurons are likely to be common across neuronal circuits.
