Molecular mechanism of intrabulbar plasticity (BDNF-CREB cascade)

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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 showed the results that intrabulbar infusion of the GABA receptor antagonist, … More bicuculline facilitates olfactory learning. 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. And we tried to clarify synaptic plasticity in the OB using electrophysiology.1)Only long-term olfactory memory was prevented by CREB antisense infusion, but short-term memory was intact.2)Western blot analysis shows that phosphorylated CREB(pCREB) increases 10 minutes after the training for 2 hours.3)MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase) phosphorylates CREB.4)Long-term potentiation(LTP) was induced in field EPSPs recorded in the granule cell layer in the OB by tetanic stimulation of the lateral olfactory tract.5)In the presence of noradrenaline subthreshold stimulation was capable of inducing LTP.6)Common properties between electrophysiology and behavior pharmacology indicate that synaptic plasticity at the dendrodendritic synapses is a major candidate for neural mechanisms underlying aversive olfactory learning in young rats. Less