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Hormones and neural circuits

Hormones and neural circuits. Lecture 4. Aims . to review main hormones actions through G-coupled receptors role of NO to describe the basic neural circuits for repetitive action to describe types of modulation by hormones simple behaviour: molluscan swimming and feeding

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Hormones and neural circuits

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  1. Hormones and neural circuits Lecture 4

  2. Aims • to review main hormones • actions through G-coupled receptors • role of NO • to describe the basic neural circuits for repetitive action • to describe types of modulation by hormones • simple behaviour: molluscan swimming and feeding • complex behaviour: insect ecdysis

  3. Hormones • Amino acid and peptide • Adenaline, acetylcholine, • oxytocin, vasopressin, CCAP • Steroids • ecdysone • Eicosanoids • leukotrienes, prostaglandins • NO

  4. NO • Nitric oxide - a gas! • synthesised from L-arginine by NOS • neurons (nNOS, epithelium eNOS) • depends on Ca concentration COO- COO- COO- + O2 C H +H3N C H + NADPH NAD+ +H3N C H NO (CH2)3 (CH2)3 (CH2)3 NOS NOS NH NH NH + C NH2+ C N OH C H H2N H2N O NH2 Arginine N-w-Hydroxyarginine Citrulline

  5. NO signalling • NO diffuses freely though cell membranes • but not very far! • half life from 3-5s • soluble guanylyl cyclase activated by NO • elevates cGMP • relaxes smooth muscle in blood vessels via PKG and an effect on IK(Ca) • important for heart-disease • nitrate (nitroglycerin) used to reduce angina

  6. Background to Viagra • cGMP normally broken down by phosphodiesterase

  7. Viagra • Sildenafil - best selling drug • selective for phosphodiesterase - type 5 [of 11] • termtadalafil [Cialis], vardenafil [Levitra]

  8. Summary • NO – local transmission as gas; no vesicles

  9. Modulation of single cells • Single cells can be rhythmic • R15 in Aplysia • sino-atrial node of vertebrate heart • Purkinje fibres of heart

  10. vertebrate heart • single cell rhythm

  11. Rhythm at sinoatrial node

  12. Modulation of heart rate activation curve:100% of If channels open here • If – hyperpolarization activated Na+ current • ACh accelerates rhythm • Adrenaline slows rhythm

  13. ivabradine • new heart drug • blocks If • (note difference from ACh)

  14. Summary • NO – local transmission as gas; no vesicles • heart: single cell rhythm • modulated in different ways to give same effect

  15. Neural circuits • central pattern generation • role of reflexes (see 632)

  16. Clione • Clione - a free swimming sea mollusc • swimming rhythm • alternation of up and down stroke of wings

  17. 78 Clione - ii 78 • reciprocal inhibition • up (8) / down (7) • post inhibitory rebound 78

  18. Faster with 5-HT • CPB1 is serotonergic heart down interneuron

  19. Molluscan feeding • Serotonin as modulator • local neural release (CGC, • hormonal signal in blood • What does it target? • How does it act?

  20. Target 1 : muscles 5-HT cAMP myomodulin

  21. Target 2 : motoneurons MCC is cerebral serotonergic cell in Aplysia; B21 is a buccal motoneuron

  22. Target 3: sensory neurons sense organ in one bathganglion in anotherStretch evokes twitches add 5-HT to sense organ use low Ca to show this effect is not due to action on ganglion

  23. Target 4: interneurons control + 5-HT fasterbigger EPSPquicker decline of EPSP B4 is a motoneuronB35 an interneuron in CPG

  24. Summary • NO – local transmission as gas; no vesicles • heart: single cell rhythm • modulated in different ways to give same effect • Serotonin: • Action on all points of network • Coordinated effect • some cells inhibited • Similar data exist for dopamine, octopamine, myomodulin, FMRFamide…

  25. Fundamental to growth and development 20-hydroxy-ecdysone juvenile hormone Manduca sexta ligature, extirpation, transplantation, injection, Insect ecdysis

  26. Fly life cycle larva (3 instars) egg pupa adult

  27. Moulting • weakening of old cuticle • formation of new cuticle • emergence • separation of old /new by air bubble (pre-ecdysis) • peristaltic waves to move forward out of old cuticle (ecdysis) • expansion : compression, intake of air (post-ecdysis)

  28. Main peptide hormones • ETH • EH • FMRFamide • CCAP • Bursicon

  29. ETH • 26 aa peptide in Manduca • 2 peptides in flies • secreted by Inka cells • in response to drop in ecdysone

  30. ETH targets

  31. Eclosion hormone (EH) • In Manduca, EH released from 2 cells in brain in response to ETH • positive feedback to Inka cells (which release more ETH …) • In Drosophila, EH thought to play lesser role; • ecdysis delayed by 4 min • similar role may be played by corazonin

  32. FMRFamide • secreted from Tv neurons • first cells to be activated by ETH • strengthen muscle contractions • Tv-KO is not lethal

  33. CCAP • CCAP from 5 pairs of SOG cells and 2 pairs/segment in abdomen • In Manduca, CCAP turns off pre-ecdysis and starts ecdysis (abdominal waves) • In Drosophila, CCAP-KO do not start contractions or evert head

  34. Bursicon • 140 aa • important in tanning • released from a subset of CCAP-cells Bursicon CCAP

  35. Sequential response to ETH

  36. Summary • NO – local transmission as gas; no vesicles • heart: single cell rhythm • modulated in different ways to give same effect • Serotonin: • Coordinated action on all points of network • Similar data exist for dopamine, octopamine, myomodulin, FMRFamide… • Ecdysis: Sequential program of hormone action

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