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

Curr Biol. 2023 Oct 23;33(20):4353-4366.e5. doi: 10.1016/j.cub.2023.08.072. Epub 2023 Sep 19.


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.

Keywords: chemogenetics; development; entorhinal-hippocampal network; olfactory bulb; oscillatory activity; recognition memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cognition
  • Entorhinal Cortex / physiology
  • Hippocampus* / physiology
  • Mice
  • Olfactory Bulb* / physiology
  • Smell / physiology