# Disruption of a selective vesicle pool upon retrograde amnesia dissociates memory at presynaptic terminals

## TL;DR

The study shows that different types of memories in fruit flies are stored in separate presynaptic vesicle pools, explaining why some memories are more vulnerable to disruption.

## Contribution

The paper identifies distinct presynaptic vesicle populations responsible for labile and consolidated memory, revealing a molecular framework for memory stability.

## Key findings

- Disruption of Synapsin clustering selectively impairs labile memory in fruit flies.
- Rab3 hyperactivation biases memory toward stabilization by displacing Synapsin.
- Selective vesicle pools at presynaptic terminals underlie labile and consolidated memory formation.

## Abstract

What determines memory stability? We show that distinct presynaptic vesicle populations underlie the labile and consolidated memories, which are simultaneously formed following odor-shock associative learning in fruit flies. These distinct synaptic mechanisms explain the selective loss of labile memory triggered by traumatic perturbations after learning. Given the evolutionarily conserved regulators of vesicle dynamics, our findings provide insights into memory consolidation across species.

A single learning episode induces both labile and consolidated forms of aversive olfactory memory in Drosophila melanogaster. Retrograde amnesia triggered by post-learning perturbations specifically impairs the labile memory. However, synaptic mechanisms for this selectivity remain elusive. Here, we show that diverse amnestic treatments, such as concussion, commonly disrupt the presynaptic clustering of Synapsin, which is required for anesthesia-sensitive memory. Consistently, targeted knockout of synaptojanin, a key regulator of the endocytic pathway, selectively impaired labile memory and the Synapsin-associated vesicles. In contrast, we identified Rab3, a small GTPase that regulates the late steps of vesicle exocytosis at the active zone, as selectively required for anesthesia-resistant memory. Rab3 hyperactivation enhanced its association with vesicles while displacing Synapsin. Strikingly, this manipulation biased memory toward stabilization at the cost of the labile component. We thus propose distinct vesicle pools at the presynaptic terminal underlie the formation of labile and consolidated memories. Thus, our work offers a molecular framework for controlling memory stability through targeted manipulation of vesicle dynamics.