Early olfactory processing is necessary for the maturation of limbic-hippocampal network and recognition

Cognitive processing requires directed interactions between several brain areas of the limbic system, such as the hippocampus (HP) and lateral entorhinal cortex (LEC). They are modulated by multiple sensory systems. During development, the olfactory system might have a particular impact on these areas in mice that at birth are blind, deaf, do not whisker and have poor motor abilities. We previously showed that neonatal olfactory activation boosts the oscillatory entrainment of LEC via mono-and polysynaptic projections from the olfactory bulb (OB). However, the long-lasting impact of olfactory inputs on the limbic function and cognitive abilities of later life is fully unknown. Thus, we chemogenetically decreased the synaptic outputs of mitral/tufted cells (M/TCs), the main projecting neurons in the OB, during postnatal days 8-10 and monitored the long-lasting consequences on the downstream areas LEC and HP, and on cognitive performance. In vivo extracellular recordings revealed that after the transient decrease of the olfactory output, the oscillatory activities of downstream areas were diminished along development, in line with the long-lasting decrease in the dendritic complexity of HP-projecting pyramidal neurons in LEC. Correspondingly, pre-juvenile mice experiencing early life manipulation had declined performance in cognitive tasks. These results indicate that the early olfactory processing before eye-opening might be critical for the functional development of cognitive abilities.