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Oxytocin modulation of neural circuits Lennart Oettl 2.11.2018 Oxytocin Discovered by Sir Henry H. Dale in 1906 Sir Henry Dale, 1904 Wellcome Physiological Laboratories Oxytocin Sir Henry Dale, 1904 Wellcome Physiological Laboratories

  1. Oxytocin modulation of neural circuits Lennart Oettl 2.11.2018

  2. Oxytocin • Discovered by Sir Henry H. Dale in 1906 Sir Henry Dale, 1904 Wellcome Physiological Laboratories

  3. Oxytocin Sir Henry Dale, 1904 Wellcome Physiological Laboratories

  4. Oxytocin • Discovered by Sir Henry H. Dale in 1906 • nine-amino-acid neuropeptide, (sequence elucidated in 1953) Sir Henry Dale, 1904 • Greek meaning: ‘‘quick birth’’ • Mainly known for its physiological roles : uterine contractions during parturition and milk ejection. Wellcome Physiological Laboratories

  5. Oxytocin • Discovered by Sir Henry H. Dale in 1906 • nine-amino-acid neuropeptide, (sequence elucidated in 1953) • Greek meaning: ‘‘quick birth’’ • Mainly known for its physiological roles : uterine contractions during parturition Sir Henry Dale and Otto Loewi and milk ejection.

  6. Ludwig & Leng, 2006 • synthesized in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus • two types of OT neurons (magnocellular and parvocellular neurons) have been identified (Swanson and Kuypers, 1980)

  7. • classical view: • magnocellular OT neurons -> posterior pituitary (release OT into the blood circulation) • parvocellular OT neurons -> exclusively to hindbrain areas, where local release of OT modulates vital body functions.

  8. magnocellular parvocellular

  9. magnocellular parvocellular Althammer & Grinevich 2017

  10. More than 2 types of Oxytocin neurons? Romanov et al 2016

  11. More than 2 types of Oxytocin neurons? Romanov et al 2016

  12. Distribution of oxytocin fibers in the brain Knobloch et al 2012

  13. Distribution of oxytocin receptors in the brain Mitre et al 2016

  14. How does OT reach its targets in the brain? • volume transmission (release from hypothalamic dendrites followed by diffusion in the extracellular space to other brain areas) • local axonal release

  15. Oxytocin Modulation of Behaviour Pedersen et al 1982

  16. Oxytocin Modulation of Behaviour Kendrick et al., Science, 1992

  17. Oxytocin Modulation of Behaviour Kendrick et al., Science, 1992

  18. Oxytocin Modulation of Behaviour Prairie vole: monogamous Montane vole: polygamous (Prairie vole) Insel & Young 2001

  19. Oxytocin Modulation of Human Behaviour

  20. Oxytocin Modulation of Human Behaviour Young & Barrett 2014

  21. Oxytocin Modulation of Human Behaviour Kirsch et al 2005 Young & Barrett 2014

  22. Oxytocin Modulation of Human Behaviour Young & Barrett 2014

  23. Oxytocin Modulation of Human Behaviour Nagasawa et al 2015

  24. Oxytocin Modulation of Human Behaviour Nagasawa et al 2015

  25. Oxytocin Modulation of Human Behaviour

  26. Oxytocin Modulation of Neural Circuits CA1 pyramidal neuron Non-pyramidal neuron Muhlethaler et al 1984

  27. Oxytocin Modulation of Neural Circuits Owen et al 2013

  28. Oxytocin Modulation of Neural Circuits CA2 pyramidal cells (K+ channel) Tirko et al 2018

  29. Oxytocin Modulation of Neural Circuits Nakajima et al 2014

  30. Oxytocin Modulation of Sensory Circuits Marlin et al 2015

  31. Oxytocin Modulation of Sensory Circuits Marlin et al 2015

  32. Oxytocin Modulation of Sensory Circuits Walum & Young 2018 Grinevich & Stoop 2018 Oettl et al 2016

  33. Oxytocin Modulation of Sensory Circuits Oettl et al 2016

  34. Oxytocin Modulation of Sensory Circuits

  35. Oxytocin Modulation of Sensory Circuits Zheng et al 2014

  36. Outstanding questions • Not much is known about the natural release of oxytocin in response to natural stimuli Hung et al 2017

  37. Conclusion • Oxytocin might play a general role in Walum & Young 2018 facilitating the flow of social information across multiple brain regions • (E-I balance, SNR)

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