Two Parallel Pathways Assign Opposing Odor Valences during Drosophila Memory Formation

Abstract

During olfactory associative learning in Drosophila, odors activate specific subsets of intrinsic mushroom body (MB) neurons. Coincident exposure to either rewards or punishments is thought to activate extrinsic dopaminergic neurons, which modulate synaptic connections between odor-encoding MB neurons and MB output neurons to alter behaviors. However, here we identify two classes of intrinsic MB γ neurons based on cAMP response element (CRE)-dependent expression, γCRE-p and γCRE-n, which encode aversive and appetitive valences. γCRE-p and γCRE-n neurons act antagonistically to maintain neutral valences for neutral odors. Activation or inhibition of either cell type upsets this balance, toggling odor preferences to either positive or negative values. The mushroom body output neurons, MBON-γ5β'2a/β'2mp and MBON-γ2α'1, mediate the actions of γCRE-p and γCRE-n neurons. Our data indicate that MB neurons encode valence information, as well as odor information, and this information is integrated through a process involving MBONs to regulate learning and memory.

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

“…Therefore, the MB is thought to store associative memory engrams as sparse and DAn-mediated modifications in the connectivity of MBns to the MBOn network, and MBOns are the primary MB effectors of behavior during memory retrieval (Aso et al, 2014b). Consistent with this model, several MBOns have been implicated in the retrieval of aversive or appetitive memories, and the response properties of some MBOns are altered to odors paired with rewarding or punishing US, or artificial DAn activation (Séjourné et al, 2011; Plaçais et al, 2013; Owald et al, 2015; Bouzaiane et al, 2015; Hige et al, 2015; Cohn et al, 2015; Perisse et al, 2016; Yamazaki et al, 2018). …”

“…A recent study failed to find a role for MBOn-γ2αʹ1 in aversive memory when tested at 2 hr after learning (Yamazaki et al, 2018). To probe this neuron’s role in short-term aversive memory, we blocked MBOn-γ2αʹ1 synaptic output via expression of temperature-sensitive shibire ( shi ts1 ; Kitamoto, 2001), either during acquisition and retrieval 1.5 min later (Figure 1E) or specifically during retrieval 5 min after acquisition (Figure 1F).…”

“…DAns belonging to the PPL1 cluster that are activated by punishing electric shock and are critical to aversive memory formation correspond to MBOns that drive approach, suggesting that these compartments are likely sites for aversive memory storage. While prior work has implicated some of these approach MBOns in aversive memory, curiously one, the MBOn-γ2αʹ1, was recently shown to play a role in appetitive memory but not aversive memory (Yamazaki et al, 2018). Thus, despite the fact that its cognate DAn belongs to the PPL1 cluster and is strongly activated by electric shock, the role of MBOn-γ2αʹ1 in aversive memory remains in question.…”

Cholinergic relay from punishment- to reward-encoding dopamine neurons signals punishment withdrawal as reward inDrosophila

“…Unlike Anatomical studies reveal both intra-and inter-compartment connections between DANs and MBONs (Aso et al, 2014a;Takemura et al, 2017), and functional studies suggest the involvement of inter-compartment connections in some forms of learning (Cognigni et al, 2018;Eschbach et al, 2019;Modi et al, 2020). MBON-γ2α'1 makes connections with a variety of DAN subsets, and is involved in appetitive and aversive short-term memory (Berry et al, 2018;Yamazaki et al, 2018) and consolidation of appetitive memories (Felsenberg et al, 2017). PPL1-γ2α'1 has also been implicated in acquisition of appetitive memories (Berry et al, 2018;Yamazaki et al, 2018), the acquisition and forgetting of aversive memories Berry et al, 2012;Placais et al, 2012;Berry et al, 2015;Aso and Rubin, 2016) and reconsolidation of CS-memory encoding absence of reward (Felsenberg et al, 2017).…”

“…MBON-γ2α'1 makes connections with a variety of DAN subsets, and is involved in appetitive and aversive short-term memory (Berry et al, 2018;Yamazaki et al, 2018) and consolidation of appetitive memories (Felsenberg et al, 2017). PPL1-γ2α'1 has also been implicated in acquisition of appetitive memories (Berry et al, 2018;Yamazaki et al, 2018), the acquisition and forgetting of aversive memories Berry et al, 2012;Placais et al, 2012;Berry et al, 2015;Aso and Rubin, 2016) and reconsolidation of CS-memory encoding absence of reward (Felsenberg et al, 2017). Here we demonstrate a role for MBON-γ2α'1 and PPL1-γ2α'1 in encoding shock withdrawal as reward during reversal learning.…”