Distinct dopamine neurons mediate reward signals for short- and long-term memories

Abstract

Drosophila melanogaster can acquire a stable appetitive olfactory memory when the presentation of a sugar reward and an odor are paired. However, the neuronal mechanisms by which a single training induces long-term memory are poorly understood. Here we show that two distinct subsets of dopamine neurons in the fly brain signal reward for short-term (STM) and long-term memories (LTM). One subset induces memory that decays within several hours, whereas the other induces memory that gradually develops after training. They convey reward signals to spatially segregated synaptic domains of the mushroom body (MB), a potential site for convergence. Furthermore, we identified a single type of dopamine neuron that conveys the reward signal to restricted subdomains of the mushroom body lobes and induces long-term memory. Constant appetitive memory retention after a single training session thus comprises two memory components triggered by distinct dopamine neurons.dopamine | learning and memory | Drosophila | mushroom body M emory of a momentous event persists for a long time.Whereas some forms of long-term memory (LTM) require repetitive training (1-3), a highly relevant stimulus such as food or poison is sufficient to induce LTM in a single training session (4-7). Recent studies have revealed aspects of the molecular and cellular mechanisms of LTM formation induced by repetitive training (8-11), but how a single training induces a stable LTM is poorly understood (12).Appetitive olfactory learning in fruit flies is suited to address the question, as a presentation of a sugar reward paired with odor induces robust short-term memory (STM) and LTM (6, 7). Odor is represented by a sparse ensemble of the 2,000 intrinsic neurons, the Kenyon cells (13). A current working model suggests that concomitant reward signals from sugar ingestion cause associative plasticity in Kenyon cells that might underlie memory formation (14-20). A single activation session of a specific cluster of dopamine neurons (PAM neurons) by sugar ingestion can induce appetitive memory that is stable over 24 h (19), underscoring the importance of sugar reward to the fly.The mushroom body (MB) is composed of the three different cell types, α/β, α′/β′, and γ, which have distinct roles in different phases of appetitive memories (11,(21)(22)(23)(24)(25). Similar to midbrain dopamine neurons in mammals (26,27), the structure and function of PAM cluster neurons are heterogeneous, and distinct dopamine neurons intersect unique segments of the MB lobes (19,(28)(29)(30)(31)(32)(33)(34). Further circuit dissection is thus crucial to identify candidate synapses that undergo associative modulation.By activating distinct subsets of PAM neurons for reward signaling, we found that short-and long-term memories are independently formed by two complementary subsets of PAM cluster dopamine neurons. Conditioning flies with nutritious and nonnutritious sugars revealed that the two subsets could represent different reinforcing properties: sweet taste and nutritional value of sugar....

Circuit Analysis of a Drosophila Dopamine Type 2 Receptor That Supports Anesthesia-Resistant Memory

“…Behavioral experiments were performed in dim red light at 80% relative humidity with 3-octanol (1/100 dilution in mineral oil presented in a cup of 14 mm diameter) and 4-methylcyclohexanol (1/150 dilution in mineral oil presented in a cup of 14 mm diameter) used as olfactory stimuli. The US was represented by a train of 12 DC pulses of 120 V administered in fast succession with 5 s intervals as originally introduced by Tully and Quinn (1985).…”

Dissection of theDrosophilaneuropeptide F circuit using a high-throughput two-choice assay

“…For example, the protocerebral anterior medial (PAM) cluster of dopamine neurons is required for normal sucrose reward (15,16). There is functional heterogeneity within this cluster, as different subsets of PAM dopamine neurons are involved in the sweet-only or sweet and nutritious sugar reward (17), as well as short-term and long-term appetitive memory formation (18). PAM dopaminergic neurons have also been shown to mediate normal water reward (8).…”

CaMKII knockdown affects both early and late phases of olfactory long-term memory in the honeybee

“…In Drosophila, memory traces were also attributed to specific brain locations, specifically to distinguish Kenyon cell (KC) types (Akalal et al, 2010;Malik et al, 2013;Yamagata et al, 2015). Moreover, changing the levels of autophosphorylated CaMKII in Drosophila in those KCs blocked MTM and LTM (Malik et al, 2013).…”