Overview of Synaptic Physiology: Types, Steps and Neurotransmitters

Overview of Synaptic Physiology: Types, Steps and Neurotransmitters

1. Synaptic Physiology Dr. Ralph C ylon M. Jacinto

2. Topic outline I. Functional A natomy of a S ynapse II. Synaptic Transmission I II . Neurotransmitters

3. Learning objectives 1. Describe the functional anatomy of a synapse: a. Compare and contrast the different types of synaptic connections morphologically and physiologically. b. Differentiate the different types of connections and their implications in the conduction of impulses: i . Convergence ii. Divergence iii. Reverberating circuits iv. Parallel circuits 2. Sequence the events in the transmission of impulses across the synapse 3. Explain the potentials that occur in the postsynaptic neuron. 4. Differentiate and explain how synaptic modulation occurs: a. Inhibition b. Facilitation c. Occlusion d. Potentiation 5. Explain how synaptic transmission may end.

4. I. Functional Anatomy of a Synapse

5. Synapse Specialized junctions primarily for communication between a neuron and another cell ( such as neuron , skeletal muscle, gland ) Types: 1. Electrical 2. Chemical

6. Electrical Synapse Gap junctions Dendrodendritic Synchronize the activity of neuronal populations

7. Chemical synapse Uses a neurotransmitter (chemical messenger) No direct communication between the neuron and the target cell Elements: 1. Presynaptic neuron 2. Synaptic cleft 3. Postsynaptic neuron/cell

8. II. Types of synaptic connections

9. Types of neuronal circuits

10. Types of neuronal circuits

11. Types of neuronal circuits

12. Topic outline I. Functional A natomy of a S ynapse II. Synaptic Transmission I II . Neurotransmitters

13. II. Synaptic Transmission

14. III. Synaptic transmission

15. Vesicle release and recycling High Ca2+  exocytosis of the vesicle contents Recycled via endocytosis

16. Vesicle release and recycling High Ca2+  vesicle to move towards the membrane Interaction of vesicle proteins and membrane proteins (SNAREs) Steps: Docking Priming Fusion Exocytosis Endocytosis/Refilling

17. P roteins for N eurotransmitter R elease 25 types of proteins: Docking, priming and fusion of vesicles SNARE proteins Synaptobrevin – v-SNAREs (vesicle) SNAP-25 and Syntaxin – t-SNAREs (terminal membrane) Synaptotagmin – Ca2+ sensor Video on neurotransmitter release

18. III. Synaptic transmission

19. Receptors Neurotransmitters in the synaptic space bind to receptors  physiologic effect Postsynaptic neuron/cell  depolarizing/repolarizing Presynaptic neuron  regulatory Types of receptors: Ionotropic/ligand-gated channels Metabotropic/G-protein coupled receptors cAMP, cGMP, Ca 2+ , DAG and IP 3

20. Post synaptic potential Action potential triggers the release of neurotransmitter (presynaptic neuron) will result in a change in potential on target cell: Neuron: EPSP/IPSP Muscle: End-plate potential Characteristics: Rapid Graded response Decremental

21. Excitatory/inhibitory post synaptic potential Affect the firing of a neuron EPSP - causes depolarization  Na + or Ca 2+ channels IPSP - causes hyperpolarization  Cl - or K + channels

22. End Plate Potential (EPP)

23. Synaptic integration Summed amplitudes of the synaptic potentials at the axon hillock Temporal summation Spatial summation

24. Summation Temporal summation - transmission of an impulse by rapid stimulation of one or more presynaptic neurons Spatial summation - transmission of an impulse by simultaneous or nearly simultaneous stimulation of two or more presynaptic neurons 

25. Synaptic Plasticity Synaptic connections can strengthen or weaken ( modulate ) over time Impt in learning and memory Results from changes in the NT release  depends on Ca 2+ Can either be: Short term – occurs w/in msec Long term – occurs longer than a minute

26. Modulation of synaptic activity Strength of synaptic potential also depends on the use/activity Both potentiation and depressive processes can occur at the same synapse. Type of modulation observed will depend on which process dominates. Facilitation Potentiation Depression

27. Facilitation “Paired-pulse facilitation” Form of short term synaptic plasticity 2 EPSPs  few msec apart Results to greater response after the 2 nd EPSP Inc in presynaptic Ca 2+  inc in NT released

28. Potentiation Form of short term plasticity Similar to facilitation  greater response after 2 nd EPSP is due to increased release of neurotransmitters Response is observed after stimulating presynaptic neuron at high frequency ( tetanically ) In some cases, depression can be observed instead of potentiation following the tetanic stimulus.

29. Synaptic Depression “Fatigue” Form of short term synaptic plasticity Stimulation  depletion of Ca 2+ and stored NT Can be related to postsynaptic desensitization Both potentiation and depressive processes can occur at the same synapse Depend on w/c predominates

30. Topic outline I. Functional A natomy of a S ynapse II. Synaptic Transmission I II . Neurotransmitters

31. III. Neurotransmitters

32. Neurotransmitters “Chemical messengers” Endogenous substances which allow the transmission of signals from one neuron across a synapse towards a neuron/muscle Classification based on activity: Excitatory – increases likelihood of firing action potential Inhibitory – decreases likelihood of firing action potential

33. Neurotransmitters Types of neurotransmitters: Amino acids – glycine, glutamate Monoamines (Derived from amino acids) – GABA, catecholamines, serotonin Polypeptides – substance P *Atypical – nitric oxide

34. Neurotransmitter Substrate Location Effect Acetylcholine Choline, Acetyl-CoA CNS, PNS Excitatory Serotonin Tryptophan CNS, Enterochromaffin cells Inhibitory GABA Glutamate CNS Inhibitory Glutamate Glutamine, α-ketoglutarate CNS Excitatory Glycine CNS Inhibitory Histamine Histidine Mast cells, basophils, hypothalamus Excitatory Norepinephrine Tyrosine CNS, PNS Excitatory Epinephrine Tyrosine Adrenal medulla Excitatory Dopamine Tyrosine CNS Inhibitory Nitric oxide Arginine CNS, GI tract Variable

35. 1) NT synthesized in the presynaptic neuron 2) NT, once synthesized, will be stored inside the vesicles. 3) If the axon terminal membrane is depolarized, exocytosis of NT occurs. 4) In the synaptic space, NT will bind to its receptors  effect 5) NT effect will be terminated by degrading enzymes. 6) NT, or products of its degradation, can be taken up by presynaptic neuron.

36. Acetylcholine ( ACh ) Substrate: Choline Acetate + Choline  ACh Rate limiting: choline availability Receptors: Nicotinic – ionotropic Muscarinic – metabotropic Degrading enzyme: Acetylcholinesterase ( AChase ) Reuptake: Choline transporter

37. Catecholamines Substrate: Tyrosine Rate limiting: Tyrosine hydroxylase 3 catecholamines: Dopamine Norepinephrine Epinephrine

38. Catecholamines Receptors - Metabotropic Dopaminergic receptors (D1-D5) α -adrenergic receptors β -adrenergic receptors Degrading enzyme: Monoamine oxidase (MAO) and Catechol-O-methyltransferase (COMT) Reuptake: Dopamine transporter (DAT) Norepinephrine transporter (NET)

39. Serotonin (5-HT) Substrate: Tryptophan Tryptophan  5-Hydroxytryptophan  5-Hydroxytryptamine Receptors: 5-HT1, -HT2 and -HT4 – metabotropic 5-HT3 - ionotropic receptor Reuptake: Serotonin transporter

40. Glutamate Amino acid  principal excitatory NT in CNS Receptors: Ionotropic glutamate receptors – AMPA, NMDA Metabotropic glutamate receptors Taken up by glial cells Converted to glutamine

41. GABA γ -aminobutyric acid Inhibitory NT in CNS Derived from glutamate Receptors: GABA A – ionotropic (Cl - channel) GABA B - metabotropic Taken up by glial cells Converted back to glutamate Glycine Amino acid  principal inhibitory NT in PNS Receptors: Ionotropic glycine receptors NMDA Taken up by glial cells or by the presynaptic neuron

42. Neuropeptides ”Peptides” that act as neurotransmitters Synthesized in the cell body  modified and stored to vesicles by the Golgi apparatus Vesicles are then transported to the axon terminal Receptors: most often metabotropic Removed by: enzyme degradation or by diffusion No reuptake mechanism

43. Nitric Oxide (NO) Atypical (novel) NT It is not stored in vesicles It is not released by calcium-dependent exocytosis (it diffuses) Its inactivation is passive It decays spontaneously It does not interact with receptors on target cells NO acts as a retrograde messenger

44. Summary Synapse and its types Synaptic transmission Events in presynaptic neuron Exocytosis of the neurotransmitter Effects on the postsynaptic neuron/cell Synaptic integration and modulation Neurotransmitters Different classifications Generic NT system

45. References Barrett, K.E., et al. 2019. Ganong’s Review of Medical Physiology . 26 th ed. McGraw-Hill: USA. Boron, W. & E. Boulpaep . 2017. M edical Physiology: A Cellular and Molecular Approach . 3 rd ed. Saunders: PA. Hall, A. 2016. Guyton and Hall: Textbook of Medical Physiology. 13th ed. Elsevier: PA. Koeppen , B.M. & B. Stanton. 2018. Berne & Levy: Physiology . 7 th ed. Mosby: PA. Online Sources: https://www.youtube.com/watch?v=R-A8YI7Ik4g

46. Lecturio Videos Nerves and Neurotransmission Postsynaptic Potential and Binding

47. One aspect of studying medicine is to connect, which is akin to neurons forming synapses to store memories, experiences and information; collaborate and integrate with others. There will be days you will be fatigued; there will be days you will be potentiated. Much like synapses, it all boils down to which predominates, and that is having the correct mindset.