Olfactory control of long-range coupling in developing prefrontal-hippocampal-entorhinal networks

• Applicants: Professorin Dr. Ileana L. Hanganu-Opatz; Professor Dr. Marc Spehr
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2016 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 302153259

• Final Report Year: 2024

Final Report Abstract

While sensory perception and cognitive processing represent constant research topics in Neuroscience, they have seldom been investigated synergistically. Although cognitive performance is maximized only through permanent interactions with the environment, contributions of sensory stimuli to cognitive processing have largely been neglected. This is particularly evident when considering the ontogeny and maturation of limbic circuits that account for memory and executive abilities. For decades, considerable efforts have shed light on the maturation principles of sensory systems by highlighting the relevance of molecular cues, spontaneous electrical activity, and experience. More recently, some complex interactions governing the wiring of memory-relevant circuitry during development have also been resolved. The mostly separate investigation of sensory and cognitive ontogeny results from the observation that most sensory systems are underdeveloped during early life. Rodents are blind and deaf, do not whisker, and have limited motor abilities during the first days of life, and therefore, the contribution of sensory inputs to limbic ontogeny has been deemed negligible. As a notable exception, the olfactory system reaches full maturity during intrauterine life, controlling mother-offspring interactions and survival, and might shape the limbic development. Whether early olfactory inputs truly drive the development of limbic networks has, however, been unknown. The goal of our joint research project has thus been to understand structural and functional principles underlying the connectivity and communication within the main and accessory olfactory bulb (MOB and AOB, respectively) and, notably, between the OB and olfactory cortex, specifically the lateral entorhinal cortex (LEC), the gatekeeper of limbic circuitry centered on hippocampus and prefrontal cortex during neonatal and juvenile development. To test our hypotheses, we investigate wiring and firing principles within the MOB and AOB, the first processing stages of olfactory inputs, as well as between the OB and LEC. Our research reveals several key features of M/AOB physiology and, notably, OB- to-LEC communication in mice during the first and second postnatal weeks. Specifically, we have shown that spontaneously generated patterns of OB electrical activity stimulate entorhinal circuits via mono- and polysynaptic axonal projections. OB-to-LEC activity is boosted by olfactory stimuli and disrupted by chronic olfactory lesions. Therefore, spontaneous and stimulus-evoked OB activity controls neuronal network maturation in LEC.

Link to the final report

https://doi.org/10.5281/zenodo.14636993

Publications

• Topology-Related Metrics and Applications for the Design and Operation of Wireless Sensor Networks. ACM Transactions on Sensor Networks, 10(3), 1-35.
  Ramos, Heitor S.; Frery, Alejandro C.; Boukerche, Azzedine; Oliveira, Eduardo M. R. & Loureiro, Antonio A. F.
  
• Interdependent Conductances Drive Infraslow Intrinsic Rhythmogenesis in a Subset of Accessory Olfactory Bulb Projection Neurons. The Journal of Neuroscience, 36(11), 3127-3144.
  Gorin, Monika; Tsitoura, Chryssanthi; Kahan, Anat; Watznauer, Katja; Drose, Daniela R.; Arts, Martijn; Mathar, Rudolf; O.'Connor, Simon; Hanganu-Opatz, Ileana L.; Ben-Shaul, Yoram & Spehr, Marc
  
• Bursting mitral cells time the oscillatory coupling between olfactory bulb and entorhinal networks in neonatal mice. The Journal of Physiology, 598(24), 5753-5769.
  Kostka, Johanna K.; Gretenkord, Sabine; Spehr, Marc & Hanganu‐Opatz, Ileana L.
  
• Gamma activity accelerates during prefrontal development. eLife, 9.
  Bitzenhofer, Sebastian H.; Pöpplau, Jastyn A. & Hanganu-Opatz, Ileana
  
• Synchronous Infra-Slow Oscillations Organize Ensembles of Accessory Olfactory Bulb Projection Neurons into Distinct Microcircuits. The Journal of Neuroscience, 40(21), 4203-4218.
  Tsitoura, Chryssanthi; Malinowski, Sebastian T.; Mohrhardt, Julia; Degen, Rudolf; DiBenedictis, Brett T.; Gao, Yuan; Watznauer, Katja; Gerhold, Kira; Nagel, Maximilian; Weber, Monika; Rothermel, Markus; Hanganu-Opatz, Ileana L.; Ben-Shaul, Yoram; Davison, Ian G. & Spehr, Marc
  
• Sparser and Less Efficient Hippocampal-Prefrontal Projections account for Developmental Network Dysfunction in a Model of Psychiatric Risk Mediated by Gene-Environment Interaction. The Journal of Neuroscience, 42(4), 601-618.
  Song, Lingzhen; Xu, Xiaxia; Putthoff, Peggy; Fleck, David; Spehr, Marc & Hanganu-Opatz, Ileana L.
  
• Systems neuroscience: A box full of tools to illuminate the black box of the brain. PLOS Biology, 21(7), e3002221.
  Wiegert, J. Simon; Spehr, Marc & Hanganu-Opatz, Ileana L.