Michael E. Hasselmo PROJECT SUMMARY Computer modeling techniques are required to understand how neurochemicals with subtle and broadly distributed effects alter brain function. In the proposed research, computer models of the olfactory system (the brain system for odor perception) will be used to aid in understanding the action of the neurochemicals acetylcholine and norepinephrine on the function of cells can affect the processing of odor memories. OBJECTIVES Research will focus on the following central questions: 1. How do the combined effects of noradrenaline and acetylcholine in the olfactory system affect the capacity of memory? Computer simulations will be used to model two components of the olfactory system: the olfactory bulb and olfactory cortex. Models will be used to analyze how modulation of inhibitory effects by acetylcholine and norepinephrine in the olfactory bulb and cortex increases the number of odor memories that can be stored by allowing them to be coded by separate populations of cells. 2. How does regulation of noradrenaline and acetylcholine in the olfactory system affect behavior in an odor learning task? Computer models will be used to analyze recent behavioral experiments in this laboratory testing how rats respond to odor pairs which share components (odor A with odor B, odor A with odor C) versus how they respond to odor pairs that do not share components (odor A with odor B, odor C with odor D). The model will generate predictions about how the response to odor pairs with shared components should differ depending on whether the response to odor pairs is based on the familiarity of the odor pair, or on whether the odor pair has been paired with a reward. 3. Does acetylcholine more strongly suppress spread of activity at synapses that have been recently increased in strength? Computer models show that storage of odor memories in the olfactory system appears to function more effectively when acetylcholine suppresses the spread of activity at recently strengthened synapses. This prevents recently stored memories from interfering with storage of new memories. In slices of olfactory cortex, we will test whether drugs that activate acetylcholine receptors more strongly suppress spread of activity at synapses which were recently strengthened by repetitive stimulation. 4. Computer models will be used to analyze the effect of acetylcholine and norepinephrine on fast and slow oscillations of activity in the olfactory system. The interaction of oscillations in the olfactory bulb and olfactory cortex will be analyzed, with an emphasis on feedback connections from the olfactory cortex back to the olfactory bulb.
