Assessment of olfaction-controlled developmental time windows with critical function for adult cognitive abilities

• Applicant: Professorin Dr. Ileana L. Hanganu-Opatz
• Subject Area: Experimental and Theoretical Network Neuroscience
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 526195732

Although the developmental principles of sensory and cognitive processing have been extensively investigated, their synergy is still largely neglected. Coordinated patterns of electrical activity, either endogenously generated or driven by sensory inputs, shape the scaffold of neural circuitry emerged under the influence of molecular cues. Especially during the critical periods, the sensory circuits are modulated by experience. Similarly, the complex limbic circuits accounting for cognitive processing that include the prefrontal cortex (PFC), hippocampus (HP), thalamic nuclei, and lateral entorhinal cortex (LEC), are refined by theta-beta band oscillatory activity. Recently, we provide first experimental data from mice that support the presence of critical periods for limbic development. At this early age, when most sensory systems are still immature (rodents are blind, deaf and do not whisker), the sense of olfaction provides the main source of environmental inputs, being critical for survival. Supported by a previous DFG grant, we demonstrated that spontaneously generated or odor-induced patterns of electrical activity in the olfactory bulb (OB) of neonatal mice activate the LEC via mono- and polysynaptic projections that, on its turn, boosts the HP-to-PFC communication. Here, we propose that activation of OB during defined time window(s) of neonatal development is critical for the adult function of LEC-HP-PFC circuits and cognitive performance. To address this hypothesis, multi-site recordings will be combined with opto- and chemogenetics in vivo as well as behavioral testing. First, the maturational dynamics and adult function of LEC-HP-PFC circuits after transient manipulation of OB activity during defined time window(s) of neonatal development will be monitored. Second, the adult cognitive performance recognition and working memory, decision making) will be tested after the OB manipulation described above. Finally, the impact of early odor exposure on adult cognitive abilities and recovery of “lost” infant memories (“Proust phenomenon”) will be assessed. The investigations will mechanistically elucidate how cognitive performance relies on early sensory imprinting.

• DFG Programme: Research Grants