Abstract
Memory is initially labile but can be consolidated into stable long-term memory (LTM) that is stored in the brain for extended periods. Despite recent progress, the molecular and cellular mechanisms underlying the intriguing neurobiological processes of LTM remain incompletely understood. Using the Drosophila courtship conditioning assay as a memory paradigm, here, we show that the LIM homeodomain (LIM-HD) transcription factor Apterous (Ap), which is known to regulate various developmental events, is required for both the consolidation and maintenance of LTM. Interestingly, Ap is involved in these 2 memory processes through distinct mechanisms in different neuronal subsets in the adult brain. Ap and its cofactor Chip (Chi) are indispensable for LTM maintenance in the Drosophila memory center, the mushroom bodies (MBs). On the other hand, Ap plays a crucial role in memory consolidation in a Chi-independent manner in pigment dispersing factor (Pdf)-containing large ventral–lateral clock neurons (l-LNvs) that modulate behavioral arousal and sleep. Since disrupted neurotransmission and electrical silencing in clock neurons impair memory consolidation, Ap is suggested to contribute to the stabilization of memory by ensuring the excitability of l-LNvs. Indeed, ex vivo imaging revealed that a reduced function of Ap, but not Chi, results in exaggerated Cl− responses to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in l-LNvs, indicating that wild-type (WT) Ap maintains high l-LNv excitability by suppressing the GABA response. Consistently, enhancing the excitability of l-LNvs by knocking down GABAA receptors compensates for the impaired memory consolidation in ap null mutants. Overall, our results revealed unique dual functions of the developmental regulator Ap for LTM consolidation in clock neurons and LTM maintenance in MBs.
Highlights
A newly formed labile memory in the brain is consolidated into a more stable long-term memory (LTM), which is maintained until recall
We have recently found that pigment dispersing factor (Pdf) in large ventral–lateral clock neuron (l-LNv) regulates the maintenance of LTM induced by courtship conditioning [9]
The evolutionarily conserved LIM homeodomain (LIM-homeodomain motif (HD)) protein Ap acts as a transcriptional activator, and it is essential for various developmental events in Drosophila [18,19,21,23]
Summary
A newly formed labile memory in the brain is consolidated into a more stable long-term memory (LTM), which is maintained until recall. Regardless of the learning paradigm, cAMP response element binding protein (CREB)-mediated transcription is essential for memory consolidation to establish LTM in Drosophila [4,5,6]. Many genes involved in memory consolidation have been identified, and its underlying molecular mechanisms are becoming elucidated [7,8]. Mushroom bodies (MBs), a higher-order brain center for learning and memory [1,2,3], play critical roles in both the consolidation and maintenance of LTM [9,10]. Despite recent progress, the molecular and cellular mechanisms underlying the consolidation and maintenance of LTM remain incompletely understood
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