Adipokines set neural tone by regulating synapse number
Energy sensing neural circuits decide to expend or conserve resources by integrating tonic steady-state energy store information with phasic signals for hunger and food intake. Tonic signals, in the form of adipose tissue-derived adipokines, set the baseline level of energy-sensing neuron activity, providing context for interpretation of phasic messages. However, the mechanism by which tonic adipokine information establishes baseline neuronal function is unclear. Here we show that Upd2, a Drosophila Leptin ortholog, regulates actin-based synapse reorganization by reducing inhibitory synaptic contacts, thereby providing a permissive neural tone for insulin release under conditions of nutrient surplus. Unexpectedly, Insulin acts on the same upstream inhibitory neurons to conversely increase synapse number, hence re-instating negative tone. Our results suggest that two surplus-sensing hormonal systems, Leptin/Upd2 and Insulin, converge on a neuronal circuit with opposing outcomes that establish tonic, energy-store-dependent neuron activity. HighlightsO_LIThe adipokine Upd2 regulates number of inhibitory synaptic contacts on Insulin neurons. C_LIO_LIUpd2 activates an actin-regulating complex of Arouser, Basigin, and Gelsolin in target neurons. C_LIO_LIArouser, Basigin, and Gelsolin reduce the extent of inhibitory contact on Insulin neurons. C_LIO_LIInsulin resets negative tone by increasing the number of synaptic contacts made by its own upstream inhibitory neurons. C_LI