Effects Of Acute Olfactory Injured In Mice On Hippocampal Learning And Memory And Reward Systems

Previous studies found that using olfactory bulbectomized or transgenic mice can cause olfactory deficit irreversible and lead to emotional disorders accompanied by learning and memory damage,while olfactory bulbectomy damages brain’s areas which can not eliminate the influence of stress with surgery.Using zinc sulfate damages olfactory epithelium which is a simple and efficient way to establish the model of olfactory deficit.In this study,it is main using behavior test and molecular biology to explore the influence and underlining mechanisms of learning and memory with hippocampus under olfactory deficit mice modal.At the same time,using electrophysiology,tracing and optogenetic tools to explore the influence of regulate and control,projection and behaviors for rewards system of ventral tegmental area of midbrain and nucleus accumbens with olfactory deficit mice.In the learning and memory of olfactory,we found that olfactory deficit within 1week can damage the memory of mirror water maze and fear condition,while olfactory deficit within 4 week can aggravate damaging the memory of fear condition.Interestingly,In protein expression,mice with olfactory deficit within 1 week completely inhibited the expression of Glu R1 associated with AMPA receptor and its phosphorylation site 831 and phosphorylation site 845 after partial fear training,partially inhibiting olfactory deficit within 4 weeks.Protein expression.After 1 hour of administration of the GABA_A receptor agonist Muscimol(1ug/ul)in the olfactory bulb,the serum corticosterone concentration in the mice increased significantly;after6 hours,the serum corticosterone concentration in the mice increased,but there was no significant difference;after 12 hours,the corticosterone concentration returned to the basal level.In the olfactory and emotional rewards,mice with olfactory deficit within 1 week down-regulated the activity of the olfactory-related brain piriform cortex(Pir),the cerebral ventral tegmental area(VTA)and the nucleus accumbens(NAc)in the reward-related brain regions’level,when different external conditions are stimulated(smell,syrup,restraint stress,morphine),the down-regulation of olfactory damage on the activity levels of the three brain regions basically obscures the difference caused by all external conditional stimuli.In the olfactory deficit within 4 weeks,we found that the activity of the three brain regions returned to normal levels,but the correlation between VTA and NAc in the 1-4 Hz,60-90 Hz band decreased.By virus tracing and optogenetics,olfactory bulb(OB)has a single synaptic projection of Pir and NAc,which can mediate conditional positional preference in mice,but has no significant effect on anxiety.In conclusion,we found impaired learning and memory in olfactory deficit mice,which was accompanied by elevated serum corticosterone levels,decreased LFP powers in VTA and NAc,we also found decreased coherences between VTA and NAc after long-term olfactory dysfunction,which indicated impaired functions in the reward system.Furthermore,activation of the pathway from olfactory bulb to the NAc elicited reward-related behavior in mice.All these results suggested that olfactory dysfunction can modulate the functions of midbrain reward system in mice,which might give some lights on the relationships between olfactory function and mental illness such as depression.