Gamma Neurons Mediate Dopaminergic Input during Aversive Olfactory Memory Formation in Drosophila

Abstract

SUMMARY Mushroom body (MB) dependent olfactory learning in Drosophila provides a powerful model to investigate memory mechanisms. MBs integrate olfactory conditioned stimuli (CS) inputs with neuromodulatory reinforcement (unconditioned stimuli, US) [1, 2], which for aversive learning is thought to rely on dopaminergic (DA) signaling [3–6] to DopR, a D1-like dopamine receptor expressed in MB [7, 8]. A wealth of evidence suggests the conclusion that parallel and independent signaling occurs downstream of DopR within two MB neuron cell types, with each supporting half of memory performance. For instance, expression of the rutabaga adenylyl cyclase (rut) in γ neurons is sufficient to restore normal learning to rut mutants [9] whereas expression of Neurofibromatosis I (NFI) in α/β neurons is sufficient to rescue NF1 mutants [10, 11]. DopR mutations are the only case where memory performance is fully eliminated [7], consistent with the hypothesis that DopR receives the US inputs for both γ and α/β lobe traces. We demonstrate, however, that DopR expression in γ neurons is sufficient to fully support short (STM) and long-term memory (LTM). We argue that DA-mediated CS-US association is formed in γ neurons followed by communication between γ and α/β neurons to drive consolidation.

Drk-mediated signaling to Rho kinase is required for anesthesia-resistant memory in Drosophila

“…36). In addition, the reported role of dopamine and serotonin in ARM (8,10,11) is consistent with the proposed structural plasticity model, as both neurotransmitters have been implicated in spine dynamics in both insects (37) and vertebrates (38,39).…”

“…It appears then that at least two circuits and parallel molecular pathways contribute to ARM (16): an Oct2β2 receptor-mediated Rsh-independent in the α′ß′ lobes (9) and an Rsh-dependent, d5HT1A serotonin receptor-mediated in the αβ (8), which also receives Dop2R-mediated signals (11). Finally, Dop1R1 and Dop2R activities in the γ lobes have been suggested to contribute to ARM (10,11). Drk, an SH2-SH3 domain adaptor protein orthologous to the mammalian Grb2, is also expressed preferentially in α/β neurons.…”

“…Proteins with demonstrated roles in ARM formation include Radish (Rsh) (5); the constitutively active atypical PKC, PKM (6); the calcium channel Bruchpilot (Brp) (7); the d5HT1A serotonin and Oct2β2 octopamine receptors (8,9); the Dop1R1, Dop2R dopamine receptors (10,11); and Protein Kinase A (12). However, whether these molecules operate in one or more ARMmediating signaling cascades is presently unclear.…”

Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation

“…A wealth of evidence suggests that aversive olfactory memory exists as a persistent neural activity ("trace") in a sparse subset of MB neurons-initially in the γ lobes lasting for several minutes and then spreading to α/β lobes for several hours (34)(35)(36). This physiological trace drives a protein-synthesis-dependent process in postsynaptic MB-V3 neurons, yielding structural change at MB::MB-V3 synapses (Fig.…”

The differential requirement of mushroom body α/β subdivisions in long-term memory retrieval in Drosophila

“…formation, consolidation and retrieval), so dissecting the neural circuits underlying is crucial for mechanistically understanding the memory processing and the pathological basis of neurological diseases associated with memory defi cits (Silva et al, 2009;van Strien et al, 2009;Small et al, 2011;Tye and Deisseroth, 2012). In Drosophila, with the power of sophisticated genetic toolbox and behavioral paradigm, extensive studies suggest a dynamic requirement for the three major subtypes of mushroom body (MB) neurons in olfactory conditioning: γ neurons server as a gateway to support memory formation by dopaminergic signal-mediated CS-US association (Blum et al, 2009;Qin et al, 2012), α'/β' neurons were transiently required to stabilize memory after training (Krashes et al, 2007) and to retrieve the immediate memory (Wang et al, 2008), and the outputs of α/β neurons are necessary for retrieving both aversive and appetitive long-term memory (LTM) (Isabel et al, 2004;Krashes et al, 2008;Trannoy et al, 2011).…”