Dopaminergic Modulation of cAMP Drives Nonlinear Plasticity across the Drosophila Mushroom Body Lobes

Abstract

SUMMARY Background Activity of dopaminergic neurons is necessary and sufficient to evoke learning-related plasticity in neuronal networks that modulate learning. During olfactory classical conditioning, large subsets of dopaminergic neurons are activated, releasing dopamine across broad sets of postsynaptic neurons. It is unclear how such diffuse dopamine release generates the highly localized patterns of plasticity required for memory formation. Results Here we have mapped spatial patterns of dopaminergic modulation of intracellular signaling and plasticity in Drosophila mushroom body (MB) neurons, combining presynaptic thermogenetic stimulation of dopaminergic neurons with postsynaptic functional imaging in vivo. Stimulation of dopaminergic neurons generated increases in cAMP across multiple spatial regions in the MB. However, odor presentation paired with stimulation of dopaminergic neurons evoked plasticity in Ca2+ responses in discrete spatial patterns. These patterns of plasticity correlated with behavioral requirements for each set of MB neurons in aversive and appetitive conditioning. Finally, broad elevation of cAMP differentially facilitated responses in the gamma lobe, suggesting that it is more sensitive to elevations of cAMP, and that it is recruited first into dopamine-dependent memory traces. Conclusions These data suggest that the spatial pattern of learning-related plasticity is dependent on the postsynaptic neurons’ sensitivity to cAMP signaling. This may represent a mechanism through which single-cycle conditioning allocates short-term memory to a specific subset of eligible neurons (gamma neurons).

Trace Conditioning in Drosophila Induces Associative Plasticity in Mushroom Body Kenyon Cells and Dopaminergic Neurons

“…This may indicate either a difference between trace conditioning (this study) and standard conditioning (published data), or a difference in other experimental parameters that may also account for inconsistencies in the published effects of odor—shock conditioning (Zhang and Roman, 2013; Boto et al, 2014; Hige et al, 2015a). …”

Dopamine Neurons Mediate Learning and Forgetting through Bidirectional Modulation of a Memory Trace

“…Other DAns, also responding to distinct and impactful stimuli, modulate other distinct compartments of the MBs (Boto et al, 2014; Cohn et al, 2015). The segregation of the US through parallel DAn→MBn (compartments) theoretically allows the encoding of independent cellular memory traces, or “memory bits,” in parallel.…”

Coincident postsynaptic activity gates presynaptic dopamine release to induce plasticity in Drosophila mushroom bodies

“…Rut-AC is proposed to function as a coincidence detector of olfactory and somatosensory inputs during olfactory learning (Boto et al, 2014; Busto et al, 2010; Heisenberg, 2003; Tomchik and Davis, 2009), suggesting that coincident AL and AFV-mediated activation of postsynaptic Kenyon cells functions to gate presynaptic dopaminergic release through a Rut-AC-dependent mechanism. Thus, simultaneous AL and AFV inputs specify the appropriate targets where DA needs to be released, while the amount of released DA may regulate the occurrence and intensity of plastic changes.…”