Serotonin Signals Modulate Mushroom Body Output Neurons for Sustaining Water-Reward Long-Term Memory in Drosophila

Abstract

Memory consolidation is a time-dependent process through which an unstable learned experience is transformed into a stable long-term memory; however, the circuit and molecular mechanisms underlying this process are poorly understood. The Drosophila mushroom body (MB) is a huge brain neuropil that plays a crucial role in olfactory memory. The MB neurons can be generally classified into three subsets: γ, αβ, and α′β′. Here, we report that water-reward long-term memory (wLTM) consolidation requires activity from α′β′-related mushroom body output neurons (MBONs) in a specific time window. wLTM consolidation requires neurotransmission in MBON-γ3β′1 during the 0–2 h period after training, and neurotransmission in MBON-α′2 is required during the 2–4 h period after training. Moreover, neurotransmission in MBON-α′1α′3 is required during the 0–4 h period after training. Intriguingly, blocking neurotransmission during consolidation or inhibiting serotonin biosynthesis in serotoninergic dorsal paired medial (DPM) neurons also disrupted the wLTM, suggesting that wLTM consolidation requires serotonin signals from DPM neurons. The GFP Reconstitution Across Synaptic Partners (GRASP) data showed the connectivity between DPM neurons and MBON-γ3β′1, MBON-α′2, and MBON-α′1α′3, and RNAi-mediated silencing of serotonin receptors in MBON-γ3β′1, MBON-α′2, or MBON-α′1α′3 disrupted wLTM. Taken together, our results suggest that serotonin released from DPM neurons modulates neuronal activity in MBON-γ3β′1, MBON-α′2, and MBON-α′1α′3 at specific time windows, which is critical for the consolidation of wLTM in Drosophila.

Hyperexcitation of Monoaminergic Neurons in the Drosophila Mushroom Body Disrupts Memory for Visually Oriented Rival-induced Prolonged Mating

“…5-HT serves as both a neurotransmitter and neuromodulator, potentiating synaptic transmission and facilitating the expression of genes involved in LTM formation (Sitaraman et al 2008(Sitaraman et al , 2012. Notably, our data and previous studies (Johnson et al 2011;Lee et al 2021) indicate that 5-HT actions via its receptors, such as 5-HT1B (Fig. 1E), are essential for LTM.…”

Independent insulin signaling modulators govern hot avoidance under different feeding states

“…Therefore, summarizing valences in MBONs might be important for achieving a suitable behavioral output [ 34 , 35 ]. There are at least 9 different types of MBONs whose dendrites are restricted to distinct subdomains of α′β′ lobes [ 34 , 36 ] ( S3H–S3P Fig ). We individually tested the involvement of these α′β′-related MBONs in regulating HAB by GtACR -mediated silencing of neuronal activity (Figs 7A , 7B and S11 ).…”

“…Therefore, summarizing valences in MBONs might be important for achieving a suitable behavioral output [34,35]. There are at least 9 different types of MBONs whose dendrites are restricted to distinct subdomains of α 0 β 0 lobes [34,36] (S3H-S3P Fig) . We individually tested the involvement of these α 0 β 0 -related MBONs in regulating HAB by GtACR-mediated silencing of neuronal activity (Figs 7A, 7B and S11). Our results showed that transient inhibition of MBON-α 0 3 (Fig 7A ) or MBON-β 0 1 activity (Fig 7B ) during behavioral assays disrupted HAB in both sated and hungry states.…”

Sleep benefits different stages of memory in Drosophila

“…Memory consolidation has been better characterized in olfactory memories. During classical olfactory conditioning, the synaptic output of the dorsal paired medial neurons (DPM) is required for memory consolidation ( Waddell et al, 2000 ; Yu et al, 2005 ; Lee et al, 2011 ; Pitman et al, 2011 ; Cervantes-Sandoval and Davis, 2012 ; Lee et al, 2021 ; Muria et al, 2021 ). DPMs are a pair of serotonergic neurons innervating the MB ( Lee et al, 2011 ; Pitman et al, 2011 ; Cervantes-Sandoval and Davis, 2012 ).…”