Study On Neural Network Of Bilateral Olfaction Information Communication And Epileptic Seizure Regulation By Olfactory Stimulation

Olfaction plays a critical role in both survival and development of animals.And it is closely related to varieties of neuropsychiatric diseases such as epilepsy,when it is impaired.Elucidation of the olfactory structures and functions would facilitate a deeper understanding of the brain and shed light on future therapeutic treatments of related diseases.Previous studies on odor receptors and their organizations have revealed the basic strategies for odor coding,which greatly advances the understanding of the olfactory system.However,current research on mammalian olfaction mainly focused on the transmission and regulation of olfactory information in unilateral brain hemisphere,and both the information exchange and structural basis between the two hemispheres are rarely studied.Based on literature research and previous experimental results,it is proposed that inter-hemispheric olfactory communication may occur at the level of the olfactory bulb and/or the olfactory cortex.In this dissertation,we aim to understand how olfactory information is transferred and shared across the bilateral hemispheres by dissecting the anatomical connectivity of bilateral olfactory areas in mice.In addition,we explored the neural circuit mechanism of olfactory stimulation regulating epileptic seizures.(1)Dissection of the shortest inter-bulbar pathway.Odor information could be shared between the bilateral olfactory bulbs,but the underlying structural basis is yet to be fully elucidated.To address this,a series of virus-based strategies were designed to identify the inter-bulbar connections anatomically.We found that the anterior olfactory nucleus served as the pivotal brain area directly bridging the bilateral olfactory bulbs through three different pathways: excitatory projection pathway,inhibitory projection pathway,and co-innervation pathway.These pathways recruiting excitatory neurons in different parts of the anterior olfactory nucleus and distinct types of bulbar neurons could potentially mediate the excitatory and inhibitory cross-bulb communications,and coordinate the activity between the olfactory bulbs.These results on the inter-bulbar neurocircuits would provide structural basis for the observed functions,and hints for further studies related to the roles of the inter-hemispheric olfactory communication.(2)Dissection of brain-wide monosynaptic input network of the piriform cortex.Piriform cortex is capable of integrating bi-nostril odor information,but the underlying neural circuit basis is unclear.To address this,the input networks to different subareas of the PC were mapped by using trans-synaptic viral tools.The results showed that the anterior piriform cortex received dense projections from the olfactory areas,and indirectly integrated inputs from both the bilateral olfactory bulbs;while the posterior piriform cortex innervated heavily by temporal areas.These findings are essential to shed light on the role of the piriform cortex in inter-hemispheric olfactory communication.(3)Dissection of the neural circuit mechanism of olfactory stimuli regulating epileptic seizures.Olfactory stimulation can affect the occurrence and development of temporal lobe epilepsy,but the underlying neural circuit mechanism is still unclear.To address this,the effects of the olfactory stimulations on the temporal lobe network and epileptic seizures were dissected by utilizing optogenetics and electrophysiological recording.It was found that the severity of the epileptic seizure is related to the synchronization level between the bilateral hippocampus;olfactory stimulations which increasing the synchronization activities of bilateral hippocampus promote the epileptic seizures;while which causing the desynchronization decrease the seizures.The findings contribute to further understanding of the neural mechanisms by which odor therapy affects seizures.In summary,this dissertation revealed the inter-bulbar pathways,and further dissected the neural network mechanism of olfactory stimulation regulating epileptic seizures.Our studies are essential to shed light on the neural circuit basis underlying the inter-hemispheric information communication,and provide a neural circuit-level basis for the prevention and treatment of epilepsy by olfactory stimulation.