A non-canonical on-demand dopaminergic transmission underlying olfactory aversive learning

Dopamine (DA) is involved in various brain functions including associative learning. However, it is unclear how a small number of DA neurons appropriately regulates various brain functions. DA neurons have a large number of release sites and release DA non-specifically to a large number of target neurons in the projection area in response to the activity of DA neurons. In contrast to this "broad transmission", recent studies in Drosophila ex vivo functional imaging studies have identified "on-demand transmission" that occurs independent on activity of DA neurons and releases DA specifically onto the target neurons that have produced carbon monoxide (CO) as a retrograde signal for DA release. Whereas broad transmission modulates the global function of the target area, on-demand transmission is suitable for modulating the function of specific circuits, neurons, or synapses. In Drosophila olfactory aversive conditioning, odor and shock information are associated in the brain region called mushroom body (MB) to form olfactory aversive memory. It has been suggested that DA neurons projecting to the MB mediate the transmission of shock information and reinforcement simultaneously. However, the circuit model based on on-demand transmission proposes that transmission of shock information and reinforcement are mediated by distinct neural mechanisms; while shock transmission is glutamatergic, DA neurons mediates reinforcement. On-demand transmission provides mechanical insights into how DA neurons regulate various brain functions.