Modulation of neural circuits: how stimulus context shapes innate behavior in Drosophila

Abstract

Remarkable advances have been made in recent years in our understanding of innate behavior and the underlying neural circuits. In particular, a wealth of neuromodulatory mechanisms have been uncovered that can alter the input-output relationship of a hereditary neural circuit. It is now clear that this inbuilt flexibility allows animals to modify their behavioral responses according to environmental cues, metabolic demands and physiological states. Here, we discuss recent insights into how modulation of neural circuits impacts innate behavior, with a special focus on how environmental cues and internal physiological states shape different aspects of feeding behavior in Drosophila.

Figure 1

Fruit odors suppress Drosophila's aversion to carbon dioxide by inhibiting propagation of CO₂ information at multiple layers of the olfactory circuit. (a) Schematic of the fly olfactory circuit for CO₂ information processing. CO₂ is detected by ab1C olfactory receptor neurons (ORNs) in the antenna. In the antennal lobe, ab1C axons synapse with projection neurons (PNs) in the V glomerulus. GABAergic local neurons (LNs) innervate multiple glomeruli and suppress PN output from the V glomerulus via dendro-dendritic inhibition. Two types of PNs that innervate the V glomerulus (PN_v) are highlighted: PN_v-1 is excitatory and receives bilateral input from the V glomeruli. PN_v-1 projects to the lateral horn and calyx of the mushroom body via the outer antennocerebral tract (oACT); PN_v-3 is inhibitory and receives input from every glomerulus in the ipsilateral antennal lobe and projects to the lateral horn and other higher brain regions (not indicated) via the medial antennocerebral tract (mACT). Fruit odors inhibit the CO₂ olfactory circuit at the antenna via lateral inhibition in a sensillum (b), at the antennal lobe via LN feed-forward inhibition (c), and at the lateral horn via parallel inhibition of an unidentified output neuron by PN_v-3 (d). Arrows indicate sites of inhibition.

Figure 2

Satiety state regulates feeding by a diverse array of neuromodulatory mechanisms. (a) Starvation regulates feeding in flies by enhancing olfactory and gustatory sensitivity and by regulating activity of central neurons that express internal nutrient sensors. These nutrient sensors include the fructose receptor, Gr43a, in the posterior superior lateral protocerebrum and a putative sodium-solute co-transporter, Cupcake, in some neurons in the ellipsoid body (EB). For simplicity, only one of the multiple, bilateral Gr43a- and Cupcake-neurons is shown. (b) By means of insulin and sNPF signaling, starvation enhances synaptic transmission between ORNs and PNs in several glomeruli. Among them, DM1 is crucial for flies' food searching behavior and receives input from ab1A ORNs that express Or42b receptor. Down regulation of insulin signaling promotes the expression of sNPF receptor (sNPFR) to enhance Ca²⁺ response at ORN synaptic terminals. We note that the precise subcellular localization of insulin receptor (InR) is unclear. For simplicity, InR is drawn near the synaptic terminal. (c) Starvation also promotes proboscis extension response (PER) in flies to facilitate feeding. Hunger elevates dopamine (DA) release from a class of interneurons in the SOG, named TH-VUM (tyrosine hydroxylase positive, ventral unpaired medial neurons), to activate a dopaminergic receptor (DopEcR) at the sugar-sensitive gustatory receptor neurons (Gr5a GRNs). Elevation of dopaminergic signaling enhances synaptic transmission from Gr5a GRNs to the central taste center, the subesophageal ganglion (SOG), to promote PER.