Local desensitization to dopamine devalues recurring behavior

Abstract

Goal achievement adjusts the relative importance of future behaviors. We use Drosophila to study this form of motivational control, finding that prior matings make males increasingly likely to abandon future copulations when challenged. Repetition-induced devaluation results from a reduction in dopamine reception by the Copulation Decision Neurons (CDNs), which mediate the decision to end matings. Dopamine signaling to the CDNs sustains matings in real time, but also triggers a lasting, β-arrestin-dependent desensitization of the D2R on the CDNs, leaving subsequent matings susceptible to disruption. When D2R desensitization is experimentally prevented, the male treats each mating as if it were his first. These findings provide a generalizable mechanism of motivational control and reveal a natural function for the long-studied susceptibility of the D2R to drug-induced inactivation.

Molecular control of temporal integration matches decision-making to motivational state

“…Dopaminergic activity in the ventral nervous system (anatomically distinct from the courtship promoting dopaminergic neurons in the brain, Extended Data Figure 11e ) motivates males to persist through threats during mating 12 by signaling through the D2 receptor on the CDNs [Miner et. al 28 ]. Thermogenetic stimulation of dopaminergic neurons using the warmth-gated cation channel TrpA1 29 dramatically increased the duration of sustained optogenetic CDN stimulation required to end matings ( Figure 4a ), suggesting that dopamine might motivate matings by restricting CDN integration, possibly via CaMKII.…”

“…Instead, high concentrations of dopamine decreased stimulation-evoked calcium in the CDNs despite effectively activating CaMKII ( Figure 4e , further quantified in Extended Data Figures 10e , f; [Miner et. al 28 ]). Increasing concentrations of dopamine increased the ability of ChR2-XXM stimulation to activate CaMKII ( Figure 4f ).…”

Long-range neuropeptide relay as a central-peripheral communication mechanism for the context-dependent modulation of interval timing behaviors

“…According to Taylor et al 68 , the use of KCNJ2 to block fru-positive Crz expressing AG neurons results in an increase in mating duration up to 100 minutes. Furthermore, the use of TNT to suppress dsx-positive CDN neurons in AG has been found to extend the mating duration by up to 100 minutes 69,71 . Our findings demonstrate that cells expressing SIFaR in AG play a crucial role in regulating LMD and SMD behaviors.…”

“…A limited number of dsx-positive neurons situated in AG have been recognized, which are composed of GABAergic and dopaminergic neurons 69 named as 'Copulation Decision Neuron (CDN)' [70][71][72] . CDN function in opposition to regulate copulation duration by modulating the behavioral state of the male fly over a period of time 68,69 .…”