Role of intrabulbar CREB synthesis in olfactory learning

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Preweanling young rats prior to eye opening are dependent on somatosensory and olfactory function for survival, as they can learn their dam's odor and approach her without visual information. In order to establish olfactory learning, the pairing of odor and somatosensory stimulation is crucial. Centrifugal noradrenergic activation through the locus coeruleus by a somatosensory stimulus is implicated in olfactory learning. Within the olfactory bulb (OB), the noradrenergic innervation modulates the efficacy of dendrodendritic synapses between the mitral and granule cells. At the dendrodendritic reciprocal synapses, mitral cell activity is inhibited by GABA released from the granule cells. LC activation is thought to modulate GABAergic inhibition of the mitral cells by the granule cells. It is noteworthy that disinhibition of the mitral cells is a crucial step in the formation of an olfactory memory.We previously demonstrated that GABAergic mechanisms in the OB are involved in the control of olfactory learning in young rats. After intrabulbar infusion of bicuculline in the presence of an odor, animals show an aversion to or reference for the neutral odor. On post-natal day 12, young rats show an aversion to an odor to which they had been exposed along with presentations of foot shock on post-natal day 11. These results implicate the OB as a critical site for olfactory learning. Since it has been reported CREB(cyclic AMP response binding protein) involves plasticity in the hippocampus, we examined whether CREB is involved in olfactory learning in young rats.1) CREB antisense infusion blocks olfactory learning.2) Western blot analysis shows that phosphorylated CREB (p CREB) increases 10 minutes after the training for 2 hours.3) Inhibitors of enzymes involved in CREB phosphrylation prevent olfactory learning, and concomitantly result in no increase of pCREB in Western blot.