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Using electrophysiology to probe neuroendocrine function

Using electrophysiology to probe neuroendocrine function. Moenter Lab incipient at the University of Michigan. Hypothalamo-pituitary gonadal axis. LH FSH. Theme 1: basic biophysics of GnRH neurons and their networks. LH. GnRH. 2. 0. 1. 3. 4. 5. Moenter et al., 1992. Hours.

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Using electrophysiology to probe neuroendocrine function

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  1. Using electrophysiology to probe neuroendocrine function Moenter Lab incipient at the University of Michigan

  2. Hypothalamo-pituitary gonadal axis LH FSH

  3. Theme 1: basic biophysics of GnRH neurons and their networks LH GnRH 2 0 1 3 4 5 Moenter et al., 1992 Hours

  4. Basic biophysics tools • In use • whole-cell patch-clamp • Ready to deploy • electrochemistry to measure GnRH • In development • combining electrochemistry with electrophysiology • network and long-term synaptic patterning • GnRH-channel rhodopsin mice • Bleeding edge • genetically encoded fluorescent reporters of membrane potential

  5. Theme 2: Steroid feedback regulation of GnRH release during the cycle hypothalamus pituitary ovary

  6. Steroid feedback tools • In use • whole-cell patch-clamp • animal models • daily surge • fixed E, P, androgen • In development • stoplight mice-goal is to identify KNDy neurons with dual transgene approach, red for dynorphin and green for kisspeptin. • mCherry GnRH GFP mice

  7. Theme 3: GnRH (and beyond) function in infertility DHT Sullivan and Moenter, PNAS 2004

  8. Irregular cycles  LH  GnRH neuron activity  testosterone  GABA drive to GnRH neurons Glucose intolerance Irregular cycles  LH pulse frequency  testosterone  GABA in CSF Glucose intolerance Insulin resistance Obesity PNA mice vs. PCOS women PNA PCOS

  9. Estrous cycles are disrupted in PNA mice Morgan, Hammes and Moenter, unpublished

  10. The MMP inhibitor galardin restores cycles in PNA mice Morgan, Hammes and Moenter, unpublished

  11. Infertility tools • In use • PNA model • In development • PNA T model-metabolic differences?? • high fat diet-induced obesity • Bleeding edge • stress models

  12. What we need • help with the “rude bits”, ovary and uterus. • people with metabolic expertise

  13. What we can offer • mouse models • training in electrophysiology • the upside: great way to understand function • the downside: great way to spend 6 mo answering a single question (read LOW throughput)

  14. Lab members Laura Burger Beth Wagenmaker Kasia Glanowska Garrett Gaskins Zhiguo Chu (??)

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