Odorant Deprivation Reversibly Modulates Transsynaptic Changes in the NR2B-Mediated CREB Pathway in Mouse Piriform Cortex

Abstract

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.

Compensatory Rapid Switching of Binasal Inputs in the Olfactory Cortex

“…A previous study showed that unilateral naris obstruction for Ͼ30 d enhances the intracortical association fiber input to the olfactory cortex of the adult rat (Best and Wilson, 2003). Unilateral naris obstruction for 5 d causes downregulation of the NMDA receptor NR2B subunit and phospho-CREB, specifically in layer IIb pyramidal cells of the mouse OC (Kim et al, 2006). These results raise the possibility that similar changes may occur in the AON during rapid compensatory switching of binasal inputs.…”

Age-related impairments in memory and in CREB and pCREB expression in hippocampus and amygdala following inhibitory avoidance training

“…CREB phosphorylation in the piriform cortex has been shown to be responsive to several stimuli (Alvarez-López et al, 2004; Dere et al, 2008; Estrada and Isokawa, 2009; Kim et al, 2006; Pandey et al, 2001a, b; Wang et al, 2007). However, this is the first study, to our knowledge, to examine CREB activation in the piriform cortex after inhibitory avoidance training, revealing no evidence for pCREB increases after training in either young or aged rats.…”

Is Brain Amyloid Production a Cause or a Result of Dementia of The Alzheimer's Type?

“…Synaptic control of BACE and AβPP products is especially well shown by unilateral closure of the external nares. Unilateral closure, blocking stimuli from reaching olfactory receptors in the olfactory epithelium, suppresses synaptic and metabolic activity both in the olfactory bulb (OB) and in downstream cortical sites [27,31]. The mitochondrial enzymes cytochrome oxidase and succinic dehydrogenase (indicators of brain metabolic activity) decline.…”