Dynamic Causal Modeling Reveals Distinct Network-Specific Effective Connectivity within Olfactory Pathway between Healthy and Aged Rats

Motivation: Presently, olfactory dysfunctions such as with aging, neurodegenerative diseases and COVID-19 remain poorly understood at the systems level despite extensive knowledge of the microcircuit changes at the olfactory bulb (OB). Goal(s): We aim to reveal the systematic abnormalities of downstream olfactory information processing from the OB in prematurely aged rats. Approach: We examined the effective connectivity of olfactory networks in both healthy and aged rat models with optogenetic fMRI and dynamic causal modeling. Results: We demonstrate that network-specific dynamics in the olfactory system between aged and healthy rats could be attributed to altered effective connectivity driven by primary olfactory regions downstream from OB. Impact: The ability to stimulate olfactory bulb excitatory neurons and model the downstream neural activity dynamics at the system level in healthy and aged animals has revealed key regions that are involved in olfactory dysfunctions, which can guide future therapeutic interventions.