THE NEUROBIOLOGY OF EARLY LEARNING

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We propose to continue our integrated investigation of the neurobiology of early olfactory learning. Our focus will be on the neurotransmitter and neurotrophic mechanisms involved in the neurobehavioral changes within the rat olfactory bulb induced by early olfactory learning. Dr. Leon will address the role of noradrenaline in the formation and expression of early olfactory learning by determining: the response of olfactory bulb neurons to noradrenergic stimulation; the possibility of a transient expression of beta noradrenergic receptors in the developing bulb; the role of alpha noradrenergic receptors in the expression of the neurobehavioral response; the function of the conditioned increase in bulb noradrenaline; the mechanism underlying the termination of the sensitive period; whether noradrenaline is a common critical factor for different reinforcing stimulation; whether "overstimulation" blocking of early olfactory learning is due to changes in noradrenergic responses. Dr. Gall will use the in situ hybridization technique to determine: the spatial localization within the olfactory bulb for both immediate early genes in response to odors presented under different stimulus conditions; the response to olfactory preference training; the dual response to novel and learned olfactory cues; the possible sharpening of the bulb response during development; the effects of early olfactory deprivation on subsequent olfactory bulb responses; whether changes in the immediate early genes can be linked to cellular changes in the expression of preproenkephalin and tyrosine hydroxylase. Dr. Neve will examine the role of GAP-43 in the early dopamine response of the bulb by: analyzing developing bulb for the expression of both GAP-43 and protein kinase C, a potential factor in the stabilization of GAP-43 mRNA; determining whether there is a change in GAP-43 and protein kinase C after early olfactory learning; changing the expression of GAP-43 in the bulb with a recombinant virus, then determining the change in dopamine release in response to early olfactory preference training; constructing transgenic mice that have a mutant form of GAP-43 to suppress dopamine release and then determining their response to olfactory preference training.