Gregg Roman

Associative Learning

In a classical conditioning paradigm, flies are presented with an odor (CS+) paired with an electric shock (US). The flies are then presented with a second odor (CS-) that is unpaired to the US. The associative memory is then measured as the number of trained flies choosing the CS- over the CS+ in a T-maze. A fly that has learned to associate the electric shock with the CS+ odor will avoid that odor within the T-maze. The mushroom body neurons in the Drosophila brain are essential for the formation of this associative olfactory memory. We are interested in understanding how the regulation of heterotrimeric G protein signaling pathways within these neurons regulate memory formation. To reach this understanding, we much first know which G protein signaling cascades are involved in associative learning. The activation of the G(s) induced cAMP pathway is known to be important for memory formation since mutations in the rutabaga adenylyl cyclase, the dunce phosphodiesterase, and two PKA subunits all lead to a reduction in learning scores. However, G(o)alpha is also expressed in the mushroom body neurons. We have recently shown that there is an absolute requirement for G(o) activity for olfactory associative learning. We are interested in exploring this phenotype further by identifying downstream effectors of this pathway, defining the effect of G(o) inhibition on the ultrastructure of mushroom body neurons, and identifying the activating G protein-coupled receptor. We will also address whether G(o) is required for responding to the conditioned or unconditioned stimulus.

roman_fig1

Exploration

Exploration comprises the specific behaviors, elicited by novelty, which permit the collection of information about unfamiliar parts of the environment. Many vertebrates, when first placed into a novel open field arena will display high levels of ambulation, which will gradually decrease down to a plateau level over the next several minutes. We have found that this response is conserved in Drosophila (movie here). We have further shown that in Drosophila, the high levels of initial activity are a response to the arena, and are not a function of the handling of the flies. Interestingly, flies that are blind or have poor visual acuity have normal levels of initial stimulated activity, however they maintain the high levels of activity for a much more extended period of time. Flies with poor olfactory acuity also have normal levels of initial activity, but with an extended duration of exploration. We have further identified mutations in two genes that result in a specific reduction in the initial exploratory activity phase of activity. Our goals for this project are to dissect the neurobiology of this behavior: determine which neurons and which molecular pathways are required for exploration. We are also interested in what the environmental stimuli that induce exploration are and what advantages this behavior offers to the fly.

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