Postsynaptic plasticity of cholinergic synapses underlies the induction and expression of appetitive and familiarity memories in Drosophila

Summary

Scientists discovered that fruit flies store memories using postsynaptic changes at cholinergic synapses, similar to how humans use postsynaptic mechanisms at glutamate synapses. Specific acetylcholine receptor subunits (α5 and α2) in brain cells called M4/6 neurons are required for different stages of memory formation. The research shows that fundamental memory storage mechanisms are conserved across evolution despite differences in the chemical messengers used.

Background

While vertebrates store memory through postsynaptic plasticity of glutamatergic synapses, invertebrates have been thought to rely primarily on presynaptic plasticity at cholinergic synapses. This study challenges that assumption by investigating whether postsynaptic mechanisms also contribute to memory formation in Drosophila.

Objective

To determine whether postsynaptic plasticity at cholinergic synapses, specifically at mushroom body output neurons, plays a role in memory storage in Drosophila. The study aimed to identify which nicotinic acetylcholine receptor subunits are required for different memory types and timescales.

Results

α5 nAChR subunits are required for immediate and 3-hour appetitive memories, while α2 subunits are required for 3-hour memory expression. The scaffold protein discs large is required for 3-hour appetitive memories. Postsynaptic plasticity can be induced independently of presynaptic neurotransmitter release. Both associative and non-associative familiarity memory formation involve changes in α2 nAChR subunit dynamics.

Conclusion

Postsynaptic plasticity at cholinergic synapses in Drosophila mushroom bodies follows similar principles to postsynaptic glutamatergic plasticity in vertebrates, with nAChR α5 and α2 subunits playing roles analogous to NMDAR and AMPAR respectively. This suggests that fundamental principles of synaptic plasticity underlying memory storage are evolutionarily conserved across phyla regardless of neurotransmitter identity.
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