Dopamine Signals Integrate Innate and Learned Sensory Valences to Regulate Short- and Long-Term Memory Dynamics in the Drosophila Brain

Core Concepts

Dopamine signals in the Drosophila mushroom body integrate innate and learned sensory valences to regulate the dynamics of short-term and long-term memory formation.

Abstract

The article investigates how the innate valence of a sensory stimulus affects the acquisition of learned valence information and subsequent memory dynamics in the Drosophila brain. Through in vivo voltage-imaging studies, the authors found that dopamine neurons (PPL1-DANs) in the Drosophila brain heterogeneously and bi-directionally encode the innate and learned valences of punishment, reward, and odor cues.
During initial conditioning, PPL1-γ1pedc and PPL1-γ2α'1 neurons control short-term memory formation, which weakens inhibitory feedback from MBON-γ1pedc>α/β to PPL1-α'2α2 and PPL1-α3 neurons. This diminished feedback allows these two PPL1-DAN neurons to encode the net innate plus learned valence of the conditioned odor cue, which then gates long-term memory formation.
The authors propose a computational model constrained by the fly connectome and their spiking data to explain how dopamine signals mediate the circuit interactions between short-term and long-term memory traces. This hybrid physiologic-anatomic mechanism may represent a general means by which dopamine regulates memory dynamics in other species and brain structures, including the vertebrate basal ganglia.

Stats

In vivo voltage-imaging studies were conducted in >500 flies undergoing olfactory associative conditioning.

Quotes

"Through time-lapse, in vivo voltage-imaging studies of neural spiking in >500 flies undergoing olfactory associative conditioning, we found that protocerebral posterior lateral 1 dopamine neurons (PPL1-DANs)4 heterogeneously and bi-directionally encode innate and learnt valences of punishment, reward, and odor cues."
"During further conditioning, this diminished feedback allows these two PPL1-DANs to encode the net innate plus learnt valence of the conditioned odor cue, which gates long-term memory formation."

Key Insights Distilled From

Dopamine-mediated interactions between short- and long-term memory dynamics - Nature

by Cheng Huang,... at www.nature.com 07-22-2024

https://www.nature.com/articles/s41586-024-07819-w

Deeper Inquiries

How might this dopamine-mediated mechanism for integrating innate and learned valences apply to memory dynamics in other species, such as vertebrates?

The dopamine-mediated mechanism described in the context, where interconnected short- and long-term memory units regulate memory via dopamine signals encoding innate and learned sensory valences, could potentially apply to memory dynamics in other species, including vertebrates. Dopamine is a key neuromodulator involved in reward processing and reinforcement learning in various organisms, and its role in integrating innate and learned valences could be conserved across species. Vertebrates, like Drosophila, likely utilize dopamine signaling to modulate memory formation and extinction based on the valence of sensory cues. The parallel learning units and feedback interconnections within the mushroom body of Drosophila may have analogous structures in vertebrate brain regions involved in memory processing, suggesting a common mechanism for flexible learning through the integration of innate and learned valences.

What other neuromodulatory systems, in addition to dopamine, might be involved in regulating the interactions between short-term and long-term memory formation?

In addition to dopamine, other neuromodulatory systems play crucial roles in regulating the interactions between short-term and long-term memory formation. One prominent neuromodulator is serotonin, which has been implicated in various aspects of memory processing, including synaptic plasticity and memory consolidation. Serotonin is known to influence the balance between short-term and long-term memory by modulating neuronal excitability and synaptic strength. Acetylcholine is another important neuromodulator involved in memory formation, particularly in the context of attention, learning, and memory consolidation. Acetylcholine acts on different receptor subtypes to regulate the encoding and retrieval of memories, impacting both short-term and long-term memory processes. Additionally, norepinephrine, histamine, and other neuromodulatory systems also contribute to the regulation of memory dynamics by modulating neuronal activity, synaptic plasticity, and network connectivity.

Could disruptions in the dopamine-mediated integration of innate and learned valences contribute to memory-related disorders or dysfunctions in Drosophila or other organisms?

Disruptions in the dopamine-mediated integration of innate and learned valences could indeed contribute to memory-related disorders or dysfunctions in Drosophila and other organisms. In Drosophila, alterations in dopamine signaling have been linked to impairments in associative learning, memory formation, and behavioral flexibility. Dysregulation of dopamine transmission can lead to aberrant valence processing, affecting the encoding and retrieval of memories associated with rewarding or aversive stimuli. Similar disruptions in dopamine-mediated memory mechanisms have been implicated in various memory-related disorders in vertebrates, such as Parkinson's disease, schizophrenia, and addiction. Changes in dopamine levels or receptor function can disrupt the balance between short-term and long-term memory, leading to cognitive deficits, impaired decision-making, and maladaptive behaviors. Understanding the role of dopamine in integrating innate and learned valences is crucial for elucidating the pathophysiology of memory disorders and developing targeted therapeutic interventions.