Olfactory bulb activity shapes the development of entorhinal-hippocampal coupling and associated cognitive abilities

• Published in: Current biology Vol. 33; no. 20; pp. 4353 - 4366.e5
• Main Authors: Chen, Yu-Nan, Kostka, Johanna K., Bitzenhofer, Sebastian H., Hanganu-Opatz, Ileana L.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 23.10.2023; Cell Press
• Subjects: chemogenetics; development; entorhinal-hippocampal network; olfactory bulb; oscillatory activity; recognition memory; olfactory bulb; development; oscillatory activity; entorhinal-hippocampal network; recognition memory; chemogenetics
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2023.08.072

The interplay between olfaction and higher cognitive processing has been documented in the adult brain; however, 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 downstream lateral entorhinal cortex (LEC) and hippocampus (HP). However, it is unclear whether early OB activity has a long-lasting impact on entorhinal-hippocampal function and cognitive processing. Here, we chemogenetically silenced 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 transient silencing reduces the performance in behavioral tests involving entorhinal-hippocampal circuits later in life. Thus, neonatal OB activity is critical for the functional LEC-HP development and maturation of cognitive abilities. [Display omitted] •Transient OB output silencing early in life decreases later LEC-HP communication•Neonatal OB output silencing persistently decreases LEC-HP responsiveness to stimuli•Neonatal OB output silencing compromises the entorhinal dendritic complexity•Cognitive abilities are long-lastingly impaired after neonatal OB output silencing Chen et al. show that transient silencing of olfactory bulb output during early development long-lastingly impairs the function and connectivity of downstream entorhinal-hippocampal networks, revealing that olfaction early in life is necessary for cognitive development.