Olfactory learning in the rat pup: a model that may permit visualization of a mammalian memory trace

Over the past 10 years considerable insight into intracellular interactions leading to long-term memory formation have been gleaned from various neural circuits within invertebrate and vertebrate species. This review suggests that, while certain intracellular signaling pathways are commonly involved across species, it is important to analyze specific neural systems because critical differences among systems appear to exist. The olfactory bulb has been used by our group to estimate the influence of neuromodulatory systems (serotonin and norepinephrine) on intracellular processes leading to learning. We describe here how activation of noradrenergic input to mitral cells increases cAMP leading to CREB phosphorylation when paired with a conditioning stimulus, odor. CREB phosphorylation is causal in odor preference learning leading to long-term memory for the odor. However, the relationship between cAMP activation and CREB phosphorylation is not straight forward; overstimulation of cAMP pathways impedes learning and prevents CREB phosphorylation. Excessive CREB phosphorylation also interferes with learning.