Cyclic nucleotide-induced bidirectional long-term synaptic plasticity in Drosophila mushroom body

J Physiol. 2024 Mar 15. doi: 10.1113/JP285745. Online ahead of print.ABSTRACTActivation of the cAMP pathway is one of the common mechanisms underlying long-term potentiation (LTP). In the Drosophila mushroom body, simultaneous activation of odour-coding Kenyon cells (KCs) and reinforcement-coding dopaminergic neurons activates adenylyl cyclase in KC presynaptic terminals, which is believed to trigger synaptic plasticity underlying olfactory associative learning. However, learning induces long-term depression (LTD) at these synapses, contradicting the universal role of cAMP as a facilitator of transmission. Here, we developed a system to electrophysiologically monitor both short-term and long-term synaptic plasticity at KC output synapses and demonstrated that they are indeed an exception in which activation of the cAMP-protein kinase A pathway induces LTD. Contrary to the prevailing model, our cAMP imaging found no evidence for synergistic action of dopamine and KC activity on cAMP synthesis. Furthermore, we found that forskolin-induced cAMP increase alone was insufficient for plasticity induction; it additionally required simultaneous KC activation to replicate the presynaptic LTD induced by pairing with dopamine. On the other hand, activation of the cGMP pathway paired with KC activation induced slowly developing LTP, proving antagonistic actions of the two second-messenger pathways predicted by behavioural study. Finally, KC subtype-specific interrogation of synapses revea...
Source: The Journal of Physiology - Category: Physiology Authors: Source Type: research