Introduction to Neural Transmission and the Neural Mechanisms of Acupuncture Analgesia Taylor C. Thorne University of North Carolina Wilmington 2016 People Try Acupuncture Therapy The Neuron and Transmission of Information Outline of Neural Transmission 1. Introduction of the Neuron 2. Anatomy of the Neuron 3. Classification of Neurons - structural - functional 4. The Electrical/Chemical Nature of the Neuron 5. Putative Neurotransmitters 6. Classical Neurotransmitters - effects of neurotransmitters 7. Postsynaptic Receptor Types 8. Activity at the Synapse 9. Antagonistic vs. Agonistic 10.Overview: Components/Functions of the Nervous System 11.The Peripheral Nervous System - somatic nervous system To better understand the process in which acupuncture - autonomic nervous system functions it is important to first grasp the understanding - sympathetic nervous system of the nature of neural transmission (aka communication - parasympathetic nervous system between neurons) within/between the central nervous - autonomic nervous supply to organs system (CNS) and peripheral nervous system (PNS) - nerves and plexuses 12.The Central Nervous System 13.Neurotransmitter Systems In the Brain - norepinephrine - dopamine - serotonin - acetylcholine 14.Brain Pain Pathways Introduction: The Neuron Facts Function • size/length • processes/transmits information via electrical- • sensory neurons can have axons that extend from chemical signals toes to the posterior column of the spinal cord • communication between neurons occurs via • over 1.5 meters in length synapses • human brain has about 100 billion neurons and 100 • activity may be… trillion synapses • excitatory • each neuron has (on average) 7,000 synaptic • inhibitory connections to other neurons • modulatory • neuronal cells do not undergo cell division • neurons are the core components of: • they are generated by stem cells • the brain and spinal cord (CNS) • neurogenesis: largely ceases during adulthood • the ganglia of the PNS • multiple types of neurons • sensory: send signals to the CNS • motor: receive signals from the CNS • interneurons: connect neurons to other neurons Anatomy of the Neuron • Dendrites: thin structures that arise from the cell body, extending/branching multiple times to create a “dendritic tree” • the majority of input to the neuron occurs here • Soma: the cell body • Myelin Sheath: fatty layer surrounding the axon responsible for providing electrical conductivity from neuron to neuron • Axon: the cellular extension from the soma at the axon hillock • the majority of information transport occurs here • aka nerve fiber when it is myelinated • nerve fibers bundle into fascicles • bundles of fascicles make up nerves in the PNS Classification of Neurons: Structural • based upon polarity • Unipolar: dendrite and axon emerge from same process • Bipolar: axon and single dendrite on opposite ends of soma • Multipolar: two or more dendrites, separate from the axon expand or make more relevant Classification of Neurons: Functional • Afferent nerves: convey information from tissues/organs into the CNS • aka sensory neurons • Interneurons: connect neurons with specific regions of CNS http://www.scholarpedia.org/article/ Interneurons • Efferent nerves: transmit signals from CNS to effector cells • aka motor neurons The Electrical/Chemical Nature of the Neuron • Action Potential (AP): an all or none, propagating electrochemical signal that travels along axon activating synaptic Threshold depolarization triggers the change connections in membrane permeability, thereby • fundamental process that triggers the activating/opening ion channels release of neurotransmitters (NTs) • positive voltage threshold must be reached for AP to fire • aka “wave of depolarization” Activating The Firing of A Neuron • Resting Membrane Potential (RMP): -70mV • Hyperpolarization: makes the resting membrane potential more negative • Depolarization: makes the resting membrane potential more positive http://www.scholarpedia.org/article/ Neuron The Electrical/Chemical Nature of the Neuron Voltage gated Na+ ion channels open only when a critical level of depolarization occurs, then other ion channels become involved need expansion for this slide? • voltage dependent ion channels: • altered by changes in cross membrane voltage • large changes in voltage can elicit action potential Knowledge Check 1. Describe the difference in function between sensory and motor neurons. Which type of neuron is afferent and which is efferent? 2. Does the activation of the action potential require hyperpolarization of the resting membrane potential or depolarization? 3. Which ion channel opens immediately following the period of critical depolarization during the action potential? Putative Neurotransmitters List of Neurotransmitters: Neurotransmitters: chemical 1. Agmatine 30. Pancreatic polypeptide (PP) signals released from 2. Aspartate (Asp) 31. Peptide YY (PYY) presynaptic nerve terminals 3. Glutamate (Glu) 32. Corticotropin (ACTH) into the synaptic cleft 4. Gamma-aminobutyric acid (GABA) 33. Enkephaline 5. Glycine (Gly) 34. Dynorphin • transmit signals across a 6. D-serine (Ser) 35. Endorphin chemical synapse (e.g. 7. Acetylcholine (Ach) 36. Orexin A (OX-A) 8. Dopamine (DA) 37. Orexin B (OX-B) neuromuscular junction) 9. Norepinephrine (NE) 38. Secretin from one neuron to another 10.Epinephrine (adrenaline) (Epi) 39. Motilin neuron or cell 11.Serotonin (5-HT) 40. Glucagon 12.Melatonin (Mel) 41. Vasoactive Intestinal peptide (VIP) • synthesized from simple 13.Histamine (H) 42. Growth Hormone Releasing Factor (GRF) amino acids 14.Phenethylamine (PEA) 43. Somatostatin 15.N-methylphenethylamine (NMPEA) 44. Neurokinin A • bind to receptors in the 16.Tyramine (TYR) 45. Neurokinin B membrane on the 17.Octopamine (Oct) 46. Substance P postsynaptic side of the 18.Synephrine (Syn) 47. Bombesin 19.3-methoxytyramine (3-MT) synapse 48. Gastrin releasing peptide (GRP) 20.Tryptamine 49. Anandamide (AEA) 21.N-methyltryptamine (NMT) 50. 2-arachidonoylglycerol (2-AG) Major Neurotransmitters: 22.N-acetylaspartylglutamate (NAAG) 51. 2-arachidonyl glyceryl ether (2-AGE) • amino acids 23.Gastrin 52. N-arachidonoyl dopamine (NADA) • gasotransmitters 24.Cholecystokinin (CCK) 53. Virodhamine • monoamines 25.Vasopressin (AVP) 54. Adenosine triphosphate (ATP) • trace amines 26.Oxytocin (OT) 55. Adenosine (Ado) • peptides 27.Neurophysin I • 28.Neurophysin II purines too much info? which ones most 29.Neuropeptide Y (NY) important - trouble finding hyperlink Classical Neurotransmitters Effects of Neurotransmitters • Inhibitory Postsynaptic Potentials (IPSPs) • Excitatory Postsynaptic Potentials (EPSPs) • hyperpolarization OR • depolarization • decrease probability of action potential • increase probability of action potential Depends on receptor subtype! hyperlink Neurotransmitters Terminology Postsynaptic Effects Acetylcholine (Ach) Cholinergic +/- Serotonin (5-HT) Serotonergic +/- GABA GABA-ergic - Glutamate (Glu) Glutamatergic + Norepinephrine (NE) Adrenergic +/- Dopamine (DA) Dopaminergic +/- Enkephalin/Endorphin +/- Many other neurotransmitters are derived from precursor proteins, the so-called peptide neurotransmitters. As many as 50 different peptides have been shown to exert their effects on neural cell function. Postsynaptic Receptor Types Ionotropic Receptors Metabotropic Receptors • aka ligand-gated ion channels • aka G-protein couple receptor • neurotransmitter binds • neurotransmitter binds • recognition by its receptor • G-protein is activated • binding of GABA to receptor • G-protein subunits or intracellular • ion channel opening messengers modulate ion channels • ions flow across membrane • ion channel opens • ions flow across membrane Hyperlink clarify/give example Activity at the Synapse hyperlink each # to examples of substances that work at that point - stars = hyperlinks Agonistic vs. Antagonistic Agonistic/Antagonistic drugs interact with neurotransmitters differently… Agonists Antagonists • mimic the effects of neurotransmitters • block the brain’s neurotransmitters • produce actions • oppose actions • two main categories • two main categories • direct-binding agonists: acts just like a neurotransmitter, • direct-acting antagonist: take up the space present on binding directly to the receptor site (allows the recipient receptors otherwise occupied by NTs (blocking the NTs to experience the effects of the drug as if released themselves from binding to receptors) directly into the brain) • example: atropine • examples: dopamine, apomorphine, nicotine • indirect-acting antagonists: inhibit the release/production • indirect-acting agonists: enhance the neurotransmitter of neurotransmitters actions by stimulating NT release • example: reserpine • example: cocaine hyperlink Overview: Components and Functions of the Nervous System http://www.scholarpedia.org/article/ Nervous_system Knowledge Check 1. Which classic neurotransmitter is strictly inhibitory while the others are both inhibitory and excitatory? 2. What are the differences between re-uptake and enzymatic degradation? 3. Is nerve gas an agonistic or antagonistic drug? Explain why the Ach receptor agonists works to inhibit the enzyme acetylcholinesterase. The Peripheral Nervous System (PNS) • consists of nerves and ganglia on outside of the brain and spinal cord • main function: connect the CNS to limbs and organs • serves as a communication relay between brain and extremities • not protected by bone or blood-brain barrier • exposed to toxins and injury • divided into two systems