Grant: Operating Grant

The ability to create associations among objects or events enriches the brain's capacity for new memories and permits a wide array of cues to trigger the recall of past memories. My proposal explores the cellular mechanisms governing memory formation in a simple mammalian associative learning model. Classical conditioning of odor preference learning in the neonatal rat provides us with an excellent model for the study of associative memory. Young rats learn to prefer odors associated with a stimulus such as stroking the pup that mimics the maternal care of licking pups. The unconditioned stimulus, stroking, is mediated by norepinephrine release in the olfactory bulb (the first odor processing center) acting at beta-adrenoceptors. The conditioned stimulus, an odor, is represented by activity in olfactory bulb mitral cells. How does norepinephrine via beta-adrenoceptor activation in the olfactory bulb promote learning? I propose to create an in vitro working model using olfactory bulb slices. The learning association will be mimicked by pairing electrical stimulation of the olfactory nerve (mimicking odor input) with application of a beta-adrenoceptor agonist. I will measure the physiological changes in different types of neurons in order to understand the circuitry underpinning the odor associative learning. I hypothesize that beta-adrenoceptor activation in the olfactory bulb facilitates the communication between olfactory receptor neurons (which form the olfactory nerve) and olfactory bulb mitral cells so that mitral cells enhance their responses to the same odor input. My proposed research in understanding one form of memory will shed light on what underneath memory loss during pathological conditions. A deeper understanding of memory mechanism in animal models has implications for the treatment of memory dysfunction in Alzheimer's disease and other age-related disorders, which significantly affect quality of life of millions of people.