Odorant deprivation reversibly modulates transsynaptic changes in the NR2B-mediated CREB pathway in mouse piriform cortex.
The olfactory system is an outstanding model for understanding activity-dependent neuronal plasticity in mammals. Olfactory sensory neurons (OSNs) in the periphery project onto mitral/tufted cells in the olfactory bulb (OB) and these mitral/tufted cells in turn project to piriform cortex (PC). Numerous studies have examined changes in OB after a permanent OSN ablation, but little is known about "trans-transsynaptic" changes taking place in the PC. Permanent zinc sulfate lesion of the olfactory epithelium resulted in a selective loss of the NMDA receptor NR2B protein and mRNA expression in pyramidal cells in layer IIb of PC after 2-7 d. Regulatory elements affected by NR2B signaling, namely the phosphorylation of CREB, were also downregulated only in layer IIb neurons. These changes could be caused by OSN axon loss in the zinc sulfate lesion, or to a reduced activity. To test this hypothesis, we performed both permanent and reversible naris occlusion, which blocks odorant access to the nasal cavities and OSN activity. The expression of NR2B and phospho-CREB were downregulated 5 d after occlusion and this reduction was fully restored 10 d after reopening of the naris. Subsequently, we identified the subset of pyramidal cells in layer IIb that are especially sensitive to the loss of odor-evoked activity using double retrograde tracers. In summary, the present study provides an initial characterization of the molecular mechanisms associated with odor stimulation on second order neuronal plasticity and phenotype in the olfactory system.
Kim
Hyun H
HH
Department of Anatomy and Neurobiology, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA.
Puche
Adam C
AC
Margolis
Frank L
FL
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D009296:Nasal Cavity / Q000293:injuries / Q000601:surgery; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000009:adverse effects; D009812:Odorants; D009830:Olfactory Bulb / Q000378:metabolism; D009833:Olfactory Pathways / Q000187:drug effects / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D012683:Sensory Deprivation / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012903:Smell / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D019287:Zinc Sulfate / Q000009:adverse effects
D017362:Cyclic AMP Response Element-Binding Protein; C121001:NR2B NMDA receptor; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D019287:Zinc Sulfate