Olfactory memory traces in Drosophila

Abstract

In Drosophila, the fruit fly, coincident exposure to an odor and an aversive electric shock can produce robust behavioral memory. This behavioral memory is thought to be regulated by cellular memory traces within the central nervous system of the fly. These molecular, physiological, or structural changes in neurons, induced by pairing odor and shock, regulate behavior by altering the neurons' response to the learned environment. Recently, novel in vivo functional imaging techniques have allowed researchers to observe cellular memory traces in intact animals. These investigations have revealed interesting temporal and spatial dynamics of cellular memory traces. First, a short-term cellular memory trace was discovered that exists in the antennal lobe, an early site of olfactory processing. This trace represents the recruitment of new synaptic activity into the odor representation and forms for only a short period of time just after training. Second, an intermediate-term cellular memory trace was found in the dorsal paired medial neuron, a neuron thought to play a role in stabilizing olfactory memories. Finally, a long-term protein synthesis-dependent cellular memory trace was discovered in the mushroom bodies, a structure long implicated in olfactory learning and memory. Therefore, it appears that aversive olfactory associations are encoded by multiple cellular memory traces that occur in different regions of the brain with different temporal domains.

Fig. 1

Olfactory processing circuit in Drosophila. A diagram of the important structures in olfactory learning and memory in the fruit fly (one hemisphere of the brain). AN, antennal nerve; ACT, antennal cerebral tract; LH, lateral horn; C, calyx; MB, mushroom body; P, peduncle; DPM, dorsal paired medial neuron. Adapted with permission from Yu et al. (2005). (Sec Color Plate 18.1 in color plate section.)

Fig. 2

The AL memory trace involves recruitment of new neurons into the representation of the learned odor and is correlated with behavioral memory. Flies were trained in an olfactory classical conditioning paradigm capable of generating short-term memory. Flies were trained with stimuli consisting of either odor alone, odor paired with shock, or other protocols (not shown). After training, flies were tested, either using a behavioral memory task or using functional imaging, for their response to the trained odor. Three-minute memory scores revealed that paired odor and shock, but not odor alone, was sufficient to form memory and behavioral avoidance of the trained odor (scores indicate the percentage of flies that demonstrated learned behavior). In the flies that were tested using functional imaging, changes in the pattern of optical reporter activity were also observed in response to training with odor and shock; specifically, activity in the PNs of glomerulus D was only elicited when these stimuli were delivered simultaneously. Pseudocolor images indicate the percentage change in fluorescence of the optical reporter during odor stimulation. In this preparation, eight glomeruli were visible and identifiable. These results correlate the cellular memory trace with learned behavior. Adapted with permission from Yu et al. (2004). (See Color Plate 18.2 in color plate section.)

Fig. 3

Branch-specific cellular memory trace in the DPM neuron. Diagram of DPM neuron and its innervation of the MB lobes with overlay of branch-specific enhancement of synaptic activity.

Fig. 4

A cellular memory trace in the MB neurons is localized to the vertical branch. The optical reporter G-CaMP was expressed in both the α (vertical) and the β (horizontal) branches of the MB neurons. Flies were conditioned in a behavioral apparatus such that they received either an odor paired with shock (CS+) or an odor not paired with shock (CS−). Forward conditioning, in which the CS + and the shock were presented simultaneously, was spread over multiple, spaced trials to generate long-term memory. As a control, backward conditioning, in which the CS+ loses its predictive value because it is delivered at the end of the shock presentation, was also tested. Twenty-four hours post-conditioning, the reporter’s response to both the CS+ and the CS− odors was measured and quantified as the percentage change in fluorescence. A significant increase in reporter activity was observed only in response to forward conditioning with the CS+ odor and only in the α branch of the MB neurons. Adapted with permission from Yu et al. (2006).

Fig. 5

Spatial and temporal cellular memory traces regulate behavior. A diagram illustrating how odor information flowing through the olfactory circuit can be regulated by distinct brain regions to create a conditioned behavioral response. Behavior is posited to be regulated by multiple regions of the brain, with different regions participating during various time windows. AL, antennal lobe; LH, lateral horn; MB, mushroom bodies; DPM, dorsal paired medial; ??, unknown downstream integrator/effector neurons. The light-gray rectangle indicates the period of activity of the PN memory trace, the medium-gray rectangle the period of activity of the DPM neuron memory trace, and the black rectangle the period of the MB memory trace. Presumably, other memory traces not yet discovered participate during period not covered by these three memory traces.