Intranasal poly(I:C)-induced inflammation alters olfactory bulb-entorhinal cortex circuit and its coupling to breathing.

The olfactory bulb (OB)-entorhinal cortex (EC) circuit is involved in odor information processing and contextualization, as well as other cognitive processes that require the proper generation of neuronal network activity patterns often synchronized with breathing and affected during rhinitis. Although both the OB and the EC frequently show clear signs of neuroinflammation and neuronal stress in response to a variety of peripheral and central proinflammatory stimuli, the functional state of the OB-EC circuit during experimental rhinitis has not been explored. To fill this gap, we explored the impact of nasal inflammation, induced by the viral mimetic polyinosinic:polycytidylic acid [poly(I:C)], on the circuit composed of the OB and EC by measuring their individual neural network activities and quantifying their functional connectivity in the absence and presence of odors. We also measured the presence of proinflammatory markers in both structures and the animals' olfaction. We found that three daily intranasal poly(I:C) administrations are enough to increase proinflammatory cytokine levels in the OB and EC and to reduce olfactory detection in a novel context. Intranasal poly(I:C)-induced inflammation leads to a reduction in the power of OB and EC neural network activity and diminishes their response to odors. Moreover, poly(I:C)-induced inflammation reduces coupling between the OB and the EC at various frequencies, including those close to the respiratory rhythm. It also reduces the coupling between the EC and breathing, which is not observed in the OB. Taken together, our findings indicate that intranasal viral infection leads to neuroinflammation in the OB-EC circuit, affecting its function and connectivity, as well as its coupling to breathing, which could contribute to the olfactory and cognitive deficits observed in rhinitis.NEW & NOTEWORTHY To understand the olfactory and cognitive deficits observed in viral rhinitis, we described the impact of nasal inflammation, induced by the viral mimetic poly(I:C), on the circuit composed of the olfactory bulb and entorhinal cortex by measuring their individual neural network activities and their functional connectivity in the absence and presence of odors. We also evaluated signs of neuroinflammation in both structures and the animals' olfaction, revealing pathological mechanisms behind neurological manifestations associated with rhinitis.