The Temporally Restricted Role of the Dopamine Receptor Dop1R2 in Memory Formation

Concepts de base

The dopamine receptor Dop1R2 is required in the α/β-lobes and α'/β'-lobes of the Drosophila mushroom body for later stages of aversive and appetitive memory formation, but is dispensable for short-term memory.

Résumé

The content discusses the role of the dopamine receptor Dop1R2 in memory formation in Drosophila. The authors generated a conditional knockout line for Dop1R2 to study its function in a spatiotemporal manner.

Key highlights:

• Dop1R2 is expressed in the mushroom body (MB) of the fly brain, a region crucial for olfactory learning and memory.
• Knocking out Dop1R2 in the whole MB or specifically in the α/β-lobes and α'/β'-lobes impairs 2-hour aversive and appetitive memory, as well as 24-hour appetitive long-term memory, but does not affect short-term memory.
• Dop1R2 is dispensable for memory formation in the γ-lobe of the MB.
• Dop1R2 likely acts through the cAMP/PKA and Ca2+ signaling pathways to regulate later stages of memory consolidation and maintenance, potentially by modulating the activity of mushroom body output neurons.
• The results highlight the spatially and temporally restricted role of the dopamine receptor Dop1R2 in the complex process of memory formation.

Stats

Dop1R2 is required in the α/β-lobes and α'/β'-lobes, but not the γ-lobe, of the mushroom body for 2-hour aversive and appetitive memory, as well as 24-hour appetitive long-term memory.

Citations

"Loss of Dop1R2 in the α/β-lobes (Figure 3C) or the α'/β'-lobes (Figure 3D) impaired 2h memory after aversive training."
"Flipping out Dop1R2 in the whole MB (Figure 3E) results in a reduced performance score for 2h reward memory."
"Flipping out dop1R2 in the whole MB causes a reduced 24h memory performance (Figure 4A)."

Idées clés tirées de

A temporally restricted function of the Dopamine receptor Dop1R2 during memory formation

by Kaldun,J. C.... à www.biorxiv.org 06-02-2024

https://www.biorxiv.org/content/10.1101/2024.05.29.594954v1

Questions plus approfondies

How do the cAMP/PKA and Ca2+ signaling pathways downstream of Dop1R2 interact to regulate different stages of memory formation

The cAMP/PKA and Ca2+ signaling pathways downstream of Dop1R2 play crucial roles in regulating different stages of memory formation. Dopamine receptors like Dop1R2 can activate these pathways through interactions with specific G-proteins.
In the cAMP/PKA pathway, Dop1R2 couples with Gαs, leading to the activation of protein kinase A (PKA) and an increase in cyclic adenosine monophosphate (cAMP) levels. This pathway is essential for transcriptional activation and the expression of immediate early genes, which are critical for long-term memory (LTM) formation. On the other hand, Dop1R2 can also activate the Ca2+ signaling pathway by coupling with Gαq. This pathway modulates internal calcium levels and can influence various cellular processes related to memory formation.
During memory formation, the cAMP/PKA pathway is involved in the stabilization and maintenance of memories, while the Ca2+ signaling pathway may play a role in the initial encoding and retrieval of memories. The interplay between these pathways allows Dop1R2 to regulate different stages of memory formation, from acquisition to consolidation and retrieval.

What other dopamine receptors or neuromodulators might compensate for the loss of Dop1R2 in the γ-lobe to maintain short-term memory function

In the γ-lobe of the Mushroom body, where Dop1R2 is not required for short-term memory (STM), other dopamine receptors or neuromodulators may compensate for the loss of Dop1R2 to maintain STM function. One potential candidate is Dop1R1, another dopamine receptor expressed in the fly brain. Dop1R1 is known to be crucial for learning and short-term memory, and its activation can lead to the elevation of cAMP levels through Gαs signaling.
Additionally, other neuromodulators like octopamine or serotonin may also play a role in compensating for the loss of Dop1R2 in the γ-lobe. These neuromodulators have been implicated in various aspects of learning and memory in Drosophila and could potentially modulate synaptic plasticity and memory processes in the absence of Dop1R2.
The compensatory mechanisms in the γ-lobe may involve a complex interplay between different neurotransmitter systems and signaling pathways to ensure the maintenance of short-term memory function despite the loss of Dop1R2.

Could the spatiotemporal requirement of Dop1R2 be leveraged to develop more targeted interventions for memory-related disorders

The spatiotemporal requirement of Dop1R2 in specific brain regions like the α/β-lobe and the α’/β’-lobe of the Mushroom body could be leveraged to develop more targeted interventions for memory-related disorders. By understanding the differential roles of Dop1R2 in distinct phases of memory formation, researchers can potentially design therapies that specifically target these regions to enhance memory function or alleviate memory deficits.
For example, drugs or interventions that selectively modulate Dop1R2 activity in the α/β-lobe and the α’/β’-lobe could be developed to improve memory consolidation or retrieval in individuals with memory impairments. By focusing on the spatial and temporal requirements of Dop1R2, personalized treatments could be tailored to address specific memory-related issues based on the underlying neural circuitry involved.
Furthermore, insights into the role of Dop1R2 in memory formation could lead to the development of novel therapeutic strategies that target dopamine receptors or related signaling pathways to enhance cognitive function and memory performance in both normal and pathological conditions. Leveraging the spatiotemporal specificity of Dop1R2 could open up new avenues for precision medicine approaches in the treatment of memory disorders.