Research
      Our view of the world is constructed largely based on the information that is provided through our sensory systems. In order to unravel the complex functions of the brain, it is critical to understand how neuronal circuits acquire, categorize, and store sensory information, as well as how the nervous system uses this information to form predictions about the world that influence future behavior. A clear understanding of how these functions are performed will require thorough knowledge of the fundamental biology of the brain, from the molecular signaling pathways within each neuron to the neuronal circuits that govern behavior. The ability to acquire and store memories, adjusting behavior adaptively based on the predictive value of past experiences, is a core function of animal nervous systems. This type of cognition relies on associative learning. I am interested in the mechanisms of associative learning at the molecular, cellular, neuronal circuit, and behavioral levels. The fruit fly Drosophila melanogaster is a powerful model organism in which olfactory associative learning can be studied across these levels using a wide variety of genetic and imaging tools. Previous research from many labs has identified many molecules that are required for olfactory memory formation in Drosophila. We also know many of the neurons that are necessary to support learning, giving a clue as to the architecture of the neuronal circuits that underlie learning. A major challenge for the future is to decipher how all of these molecules and neurons function in the brain’s circuits to orchestrate learning and memory.

      My recent work in the lab of Dr. Ronald Davis has used optical imaging to examine cAMP dynamics in the Drosophila mushroom bodies, which are critical structures for olfactory associative learning in flies. We found that application of neurotransmitters that simulate an odor (the conditioned stimulus) and punishment (the unconditioned stimulus) trigger a synergistic increase in cAMP in the mushroom body neurons (Tomchik and Davis, 2009). This synergy was dependent on the rutabaga (rut) type-I adenylyl cyclase (AC), as it was absent in mutants that express a defective rut AC. The synergistic elevation of cAMP was restricted to the axons of the mushroom body neurons. In addition, it was observed only when the neurotransmitter stimuli were paired in the correct temporal order and within the appropriate time window for behavioral conditioning. These data provide evidence that the rutabaga AC functions as a coincidence detector underlying associative learning in Drosophila.



Taste cells Focal tastant application

The Drosophila brain


Both images are confocal z-stacks of different parts of the Drosophila brain expressing yellow fluorescent protein. The image on the left is of the antennal lobe (homolog of the olfactory bulb), and the image on the right is of the mushroom body. Both areas are critical for olfactory memory in flies.



      Currently, I am focusing my research on several areas. First, I am studying the roles of candidate signaling molecules that are potentially involved in learning. In addition, I am looking at how major signaling pathways (such as cAMP/PKA) are activated during learning, and how activation of these pathways affects the responses of the neurons that encode memories. Finally, I am examining the way that neuronal responses are altered across the arrays of neurons that encode memories. In pursuit of these goals, I am using imaging of with newly-developing calcium and cAMP reporters in both live flies and in isolated, intact brains. These imaging techniques, combined with behavioral analysis of mutant and wild-type flies, provide a method to probe the function of molecules, neurons, and circuits involved in memory formation in detail.