Odorant deprivation reversibly modulates transsynaptic changes in the NR2B-mediated CREB pathway in mouse piriform...

Area of Science:

• Neuroscience
• Olfactory System Research
• Neuronal Plasticity

Background:

• The olfactory system serves as a model for studying activity-dependent neuronal plasticity.
• While olfactory bulb (OB) changes after sensory neuron loss are known, trans-transsynaptic alterations in the piriform cortex (PC) remain unclear.

Purpose of the Study:

• To investigate trans-transsynaptic molecular changes in the PC in response to olfactory sensory neuron (OSN) activity loss.
• To characterize the molecular mechanisms underlying odor stimulation's effect on second-order neuronal plasticity.

Main Methods:

• Permanent zinc sulfate lesion of olfactory epithelium to induce OSN ablation.
• Permanent and reversible naris occlusion to block odorant access and OSN activity.
• Analysis of NMDA receptor NR2B and phosphorylated CREB (pCREB) expression in PC layers.
• Utilized double retrograde tracers to identify activity-sensitive pyramidal cells.

Main Results:

• Zinc sulfate lesion caused selective downregulation of NR2B and pCREB in PC layer IIb pyramidal cells.
• Naris occlusion led to reduced NR2B and pCREB expression, which was fully restored upon reopening the naris.
• Identified specific layer IIb pyramidal cells highly sensitive to the loss of odor-evoked activity.

Conclusions:

• Odor-evoked activity regulates NR2B and pCREB expression in PC layer IIb neurons, indicating activity-dependent plasticity.
• These findings provide initial insights into the molecular mechanisms of olfactory system plasticity beyond the OB.