Neuropeptide F inhibits dopamine neuron interference of long-term memory consolidation in Drosophila

Abstract

Long-term memory (LTM) formation requires consolidation processes to overcome interfering signals that erode memory formation. Olfactory memory in Drosophila involves convergent projection neuron (PN; odor) and dopaminergic neuron (DAN; reinforcement) input to the mushroom body (MB). How posttraining DAN activity in the posterior lateral protocerebrum (PPL1) continues to regulate memory consolidation remains unknown. Here we address this question using targeted transgenes in behavior and electrophysiology experiments to show that (1) persistent post-training activity of PPL1-a2a 0 2 and PPL1-a3 DANs interferes with aversive LTM formation; (2) neuropeptide F (NPF) signaling blocks this interference in PPL1-a2a 0 2 and PPL1-a3 DANs after spaced training to enable LTM formation; and (3) training-induced NPF release and neurotransmission from two upstream dorsal-anterior-lateral (DAL2) neurons are required to form LTM. Thus, NPF signals from DAL2 neurons to specific PPL1 DANs disinhibit the memory circuit, ensuring that periodic events are remembered as consolidated LTM.

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

“…The precise integration of these monoamines within speci c neural circuits, such as the MB g-Kenyon cells, enables the encoding and retrieval of LTM in Drosophila. Our ndings align with previous reports suggesting that inhibitory circuits within MB play a pivotal role in the generation of LTM (Aranda et al 2017;Awata et al 2019;Feng et al 2021) (Fig. 2U).…”

“…The following lines were obtained from kyoto drosophila stock center (#stock number): GAL4 NP5270 (Kyoto # 113657). GAL4 [14][15][16][17][18][19] was kind gift from Dr. Ulrike Heberlein (HHMI Janelia Ressearch Campus)…”

Brief Change in Dopamine Activity during Consolidation Impairs Long-Term Memory via Sleep Disruption

“…Persistent activity in PPL1-γ1pedc and -γ2α’1 subtypes interferes with STM and anesthesia-resistant memory (ARM), and promotes forgetting (Berry et al, 2015; Berry et al, 2012; Placais et al, 2012). PPL1-α2α’2 and PPL1-α3 mediate aversive LTM formation with persistent post-training activity (Feng et al, 2021). A delayed post-training activity in aSP13-DANs is required for LTM consolidation of courtship learning (Kruttner et al, 2015).…”

Nutrient responding peptide hormone CCHamide-2 consolidates appetitive memory

“…Neuropeptide F, another important regulator of feeding (Chung et al, 2017;Tsao et al, 2018;Landayan et al, 2021), foodrelated memory (Krashes et al, 2009;Rohwedder et al, 2015), and lipid metabolism (Yoshinari et al, 2021), also acts as a disinhibitory gate for LTM consolidation (Feng et al, 2021). Thus, metabolic peptide hormones (Lin et al, 2019;Nässel et al, 2019) appear crucial in linking alimentary and memory consolidation processes for triggering LTM.…”

“…In accordance, insulin signaling, a crucial regulator of metabolic homeostasis ( Rulifson et al, 2002 ), is implicated in the formation of LTM both in larvae and adult flies ( Chambers et al, 2015 ; Eschment et al, 2020 ). Neuropeptide F, another important regulator of feeding ( Chung et al, 2017 ; Tsao et al, 2018 ; Landayan et al, 2021 ), food-related memory ( Krashes et al, 2009 ; Rohwedder et al, 2015 ), and lipid metabolism ( Yoshinari et al, 2021 ), also acts as a disinhibitory gate for LTM consolidation ( Feng et al, 2021 ). Thus, metabolic peptide hormones ( Lin et al, 2019 ; Nässel et al, 2019 ) appear crucial in linking alimentary and memory consolidation processes for triggering LTM.…”