# Global and local missions of cAMP signaling in neural plasticity, learning, and memory

## TL;DR

This paper explores how cAMP signaling in fruit flies affects neural plasticity, learning, and memory through global and local mechanisms.

## Contribution

The paper highlights a dual regulatory role of cAMP in modulating excitatory and inhibitory synaptic plasticity in Drosophila.

## Key findings

- cAMP signaling increases excitatory neural circuit strength and memory.
- cAMP locally reduces inhibitory synaptic plasticity via GABA receptors.
- Mutations in rutabaga and dunce genes impair associative learning in Drosophila.

## Abstract

The fruit fly Drosophila melanogaster has been a popular model to study cAMP signaling and resultant behaviors due to its powerful genetic approaches. All molecular components (AC, PDE, PKA, CREB, etc) essential for cAMP signaling have been identified in the fly. Among them, adenylyl cyclase (AC) gene rutabaga and phosphodiesterase (PDE) gene dunce have been intensively studied to understand the role of cAMP signaling. Interestingly, these two mutant genes were originally identified on the basis of associative learning deficits. This commentary summarizes findings on the role of cAMP in Drosophila neuronal excitability, synaptic plasticity and memory. It mainly focuses on two distinct mechanisms (global versus local) regulating excitatory and inhibitory synaptic plasticity related to cAMP homeostasis. This dual regulatory role of cAMP is to increase the strength of excitatory neural circuits on one hand, but to act locally on postsynaptic GABA receptors to decrease inhibitory synaptic plasticity on the other. Thus the action of cAMP could result in a global increase in the neural circuit excitability and memory. Implications of this cAMP signaling related to drug discovery for neural diseases are also described.