Brief disruption of activity in a subset of dopaminergic neurons during consolidation impairs long-term memory by fragmenting sleep

Sleep disturbances are linked to poor long-term memory formation, but the specific cell types and neural circuits involved remain unclear. Researchers investigated the role of dopamine neurons (DANs) in memory processing. Using both male and female flies, they discovered that briefly altering the activity of a small subset of protocerebral anterior medial DANs (PAM-DANs) during the first hours of memory consolidation impairs 24-hour long-term memory (LTM).

This effect was more pronounced in female flies, leading to sleep loss and fragmentation, particularly at night. Pharmacological intervention to restore sleep after manipulation helped restore LTM.

The study identified a specific subset of PAM-DANs (PAM-α1) that synapse onto DPM neurons as crucial to linking sleep and memory. Another subset, MBON-α1, also contributes to this integration by acting as an additional parallel circuit. PAM-DANs, including PAM-α1, form functional synapses with DPM mainly through two dopamine receptor subtypes.

Dop1R1 primarily mediates the connection between sleep and memory. The PAM-α1 to DPM microcircuit displays a synchronized, temporary change in activity during the key memory consolidation period, suggesting its role in maintaining the sleep necessary for LTM formation. The findings offer a new molecular and circuit basis for the intricate relationship between sleep and memory.