New insights into how the function of nerve cells and their synaptic connections is controlled by multiple modulatory substances at the same time

Under the guidance of Dirk Bucher and Farzan Nadim, both faculty in the department, Dr. Li used a small neural circuit in crabs for her dissertation work to show that the way two modulatory neuropeptides act together can be very different at different subcellular targets. Their combined effect on synapses was simply the sum of their individual effects. In contrast, the combined effect on voltage-gated ion channels was smaller than could be predicted from the individual effects, particularly if the two peptides were present at different concentrations. This is an important finding, as neuromodulators play a crucial role in adjusting the activity of all neural circuits to different behavioral requirements, for example sleep vs wakefulness, walking vs running, or how frequently and deeply we breathe. Much research has been done to understand the actions of single neuromodulators from the cellular to the circuit level. However, most neurons and synapses are under the control of multiple neuromodulators at all times. How the effects of those different substances combine is generally not well understood.

Figure: The effect of activating receptors for two different neuropeptides that have shared targets. At the synapse, the combined effect is the linear sum of the separate effect. At a voltage-gated ion channel, the combined effect is sublinear, which can be explained by inhibitory interactions between the signaling pathways.