Acetylcholine

• How do neurons regulate the release of their neurotransmitters?

  By auto-receptors
• Auto-receptors


  Found on the presynaptic membrane of many times of neurons; they sense elevated presence of neurotransmitters and reduce release
• Where do Acetylcholine neuronal cell bodies live?

  Basal Forebrain
• Where do Acetylcholine axons project onto other neurons?

  Cortex & Hippocampus
• What effect does Acetylcholine have?

  Blocks sympathetic nervous system; therefore, activating the parasympathetic nervous system
• What areas does the Cholinergic System innervate?

  Areas associated with memory & learning

  Frontal, parietal, occipital cortex; hippocampus, nucleus basalis, medial septal nucleus
• Where do cholinergic neurons project to?

  Brain regions with diverse functions (i.e. movement, judgement, reward, memory, pain, coordination, vision, sensation)
• What happens when you're expecting something important to occur?

  Acetylcholine levels rise over the frontal lobes of the brain
• What inhibits the rise of Acetylcholine in the frontal lobes?

  Scopolamine (the wave does not develop)
• Is there any Ach outside of the brain?

  Yes, in the autonomic nervous system (sympathetic and parasympathetic ganglionic neurons)
• Neuromuscular Junction


  All of the motor neurons from the spinal cord release Ach onto muscles
• What in the body is at risk of failing when Ach production or release is lost?

  Diaphragm
• Myasthenia Gravis


  Attack on the nicotinic acetylcholinic receptor on the muscles that open the eyelids; effect of the Ach receptor is messed up
• What causes Myasthenia Gravis?


  An autoimmune attack on nicotine receptors at the neuromuscular junction
• What does Ach do in the CNS?

  Works in the brain: memory, cognition, attention, expectation
• PNS


  ANS: organs (lungs, eyes)

  NMJ (moves muscles)
• Ach Synthesis


  Acetyl: made of glucose from the diet in the mitochondria and transported out

  
  

  Choline: comes from the diet (found in many common foods)(lecithin)
• What's OTC that contains Choline and why?


  OSU RPAC smoothies (Smart Blend) supplement that assists in memory
• CHAT & where it's produced

  Enzyme found in Ach neurons;
• Where and what produces CHAT?

  The soma by DNA
• How is CHAT transported to the terminals?

  Slow axoplasmic transport
• Where is Ach synthesized?


  In the cytoplasm of the axon terminal
• Where is a portion of Ach transported to in the synapse?

  Into vesicles for storage and release
• How is the synthesis of Ach regulated?

  If too much is being produced, negative feedback occurs and production is turned off
• Does putting more choline in the diet increase Ach production?

  No
• What prevents the release of Ach? What are the effects?

  Botulinus Toxin; Can kill by asphyxiation
• What enhances the release of Ach? How?

  Black widow spider venom; All Ach stores are released, depleting the nerve of anymore Ach
• What's the effect of black widow spider venom?

  Death by asphyxiation
• Why does asphyxiation occur from Botox and black widow spider venom?

  It controls the NMJ of the diaphragm, and if that's not working it causes you to stop breathing
• Is there any re-uptake of Ach?

  No
• What metabolizes Ach?


  AchE (acetylcholinesterase)
• What is AcH metabolized to?

  Choline and acetate
• What happens to 35-40% of the choline taken up to the terminal?

  It's recycled
• What is the function of AchE?


  To regulate Ach levels
• What happens when AchE is inhibited?

  Ach level increases
• What is a reversible inhibitor of Ache?


  Physostigmine
• Where does Physostigmine work?

  CNS & PNS
• What was Physostigmine discovered to help treat in the 1930's? How does it treat them?

  Myasthenia Gravis; it inhibits AchE at the transmitted sights of Ach, enhancing Ach release
• What other disease can AchE Inhibitors be used for? Why?

  Alzheimers; because loss of Ach causes a loss in memory, so it's used to enhance the release
• What are the irreversible inhibitors of AchE? (4)

  Insecticides, nerve gasses, sarin, atropine