Abstract
A powerful feature of adaptive memory is its inherent flexibility. Alcohol and other addictive substances can remold neural circuits important for memory to reduce this flexibility. However, the mechanism through which pertinent circuits are selected and shaped remains unclear. We show that circuits required for alcohol-associated preference shift from population level dopaminergic activation to select dopamine neurons that predict behavioral choice in Drosophila melanogaster. During memory expression, subsets of dopamine neurons directly and indirectly modulate the activity of interconnected glutamatergic and cholinergic mushroom body output neurons (MBON). Transsynaptic tracing of neurons important for memory expression revealed a convergent center of memory consolidation within the mushroom body (MB) implicated in arousal, and a structure outside the MB implicated in integration of naïve and learned responses. These findings provide a circuit framework through which dopamine neuronal activation shifts from reward delivery to cue onset, and provide insight into the maladaptive nature of memory.
Highlights
An organism’s behavior is guided by memories of past experiences and their associated positive or negative outcomes
Dopamine neurons innervating the mushroom body are required for alcohol reward associations Dopamine has a long-standing role in addiction and a defined role in reward-related behavioral learning that spans across species (Wanat et al, 2009; Yoshimoto et al, 1992; Hyman et al, 2006; Robbins and Everitt, 2002; Torregrossa et al, 2011; Kaun et al, 2011; Scaplen and Kaun, 2016)
Further decreasing dopamine-2-like receptors (D2R), which are thought to act as auto-receptors, (Vickrey and Venton, 2011), in protocerebral anterior medial (PAM) neurons significantly reduced preference for cues associated with ethanol suggesting that the regulation of dopamine release at the synapse is important for alcohol reward memory (Figure 1C)
Summary
An organism’s behavior is guided by memories of past experiences and their associated positive or negative outcomes. Drosophila form persistent appetitive memories for the pharmacological properties of alcohol that last up to 7 days post acquisition and impel flies to walk over a 120V electric shock in the presence of associated cues (Kaun et al, 2011; Nunez et al, 2018). This suggests that Drosophila and mammalian alcohol-associated memories are inflexible in the face of aversive consequences. Our results provide an in vivo circuit framework for how drugs of abuse temporally regulate acquisition and expression of sensory memories, which results in a shift in behavioral response from malleable to inflexible
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
