Olfactory control of cognitive development

The interplay between olfaction and higher cognitive processing has been documented in the adult brain, yet its development is poorly understood. In mice, shortly after birth, endogenous and stimulus-evoked activity in the olfactory bulb (OB) boosts the oscillatory entrainment of the downstream lateral entorhinal cortex (LEC) and hippocampus (HP). The tight anatomical connections between olfactory system and higher-order neuronal circuits might implicate the functional impact of olfactory outputs on cognitive functions along brain development. However, it is unclear whether early OB activity has a long-lasting impact on entorhinal-hippocampal function and cognitive processing. Here, we chemogenetically inhibited the synaptic outputs of mitral/tufted cells, the main projection neurons in the OB, during postnatal days 8-10. The transient manipulation leads to a long-lasting reduction of oscillatory coupling and weaker responsiveness to stimuli within developing entorhinal-hippocampal circuits accompanied by dendritic sparsification of LEC pyramidal neurons. Moreover, the early olfactory experience during this sensitive period influences the behavioral performance of mice later in life. Thus, the early olfactory activity is critical for the functional LEC-HP development and maturation of cognitive abilities.