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2. Neural Communication: Basics 2

3. Neurons cell body dendrites (input structure)  receive inputs from other neurons  perform spatio-temporal integration of inputs  relay them to the cell body axon (output structure)  a fiber that carries messages (spikes) from the cell to dendrites of other neurons 3

4. postsynaptic neuron science-education.nih.gov 4

5. Synapse site of communication between two cells formed when an axon of a presynaptic cell “connects” with the dendrites of a postsynaptic cell 5

6. Synapse axon of presynaptic neuron dendrite of postsynaptic neuron bipolar.about.com/library 6

7. Synapse a synapse can be excitatory or inhibitory arrival of activity at an excitatory synapse depolarizes the local membrane potential of the postsynaptic cell and makes the cell more prone to firing arrival of activity at an inhibitory synapse hyperpolarizes the local membrane potential of the postsynaptic cell and makes it less prone to firing the greater the synaptic strength, the greater the depolarization or hyperpolarization 7

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9. Neural Communication: 1 Communication within and between cells

10. Transmission of information Information must be transmitted within each neuron and between neurons 10

11. The Membrane The membrane surrounds the neuron. It is composed of lipid and protein. 11

12. The Resting Potential There is an electrical charge across the membrane. This is the membrane potential. The resting potential (when the cell is not firing) is a 70mV difference between the inside and the outside. inside outside Resting potential of neuron = -70mV + - + - + - + - + - 12

13. Artist’s rendition of a typical cell membrane 13

14. Ions and the Resting Potential Ions are electrically-charged molecules e.g. sodium (Na+), potassium (K+), chloride (Cl-). The resting potential exists because ions are concentrated on different sides of the membrane.  Na + and Cl - outside the cell.  K + and organic anions inside the cell. inside outside Na + Cl - Na + K+K+ Cl - K+K+ Organic anions (-) Na + Organic anions (-) 14

15. Ions and the Resting Potential Ions are electrically-charged molecules e.g. sodium (Na+), potassium (K+), chloride (Cl-). The resting potential exists because ions are concentrated on different sides of the membrane.  Na + and Cl - outside the cell.  K + and organic anions inside the cell. inside outside Na + Cl - Na + K+K+ Cl - K+K+ Organic anions (-) Na + Organic anions (-) 15

16. Maintaining the Resting Potential Na+ ions are actively transported (this uses energy) to maintain the resting potential. The sodium-potassium pump (a membrane protein) exchanges three Na + ions for two K + ions. inside outside Na + K+ Na + 16

17. Neuronal firing: the action potential The action potential is a rapid depolarization of the membrane. It starts at the axon hillock and passes quickly along the axon. The membrane is quickly repolarized to allow subsequent firing. 17

18. Before Depolarization 18

19. Action potentials: Rapid depolarization When partial depolarization reaches the activation threshold, voltage-gated sodium ion channels open. Sodium ions rush in. The membrane potential changes from -70mV to +40mV. Na + - + + - 19

20. Depolarization 20

21. Depolarization 21

22. Action potentials: Repolarization Sodium ion channels close and become refractory. Depolarization triggers opening of voltage-gated potassium ion channels. K+ ions rush out of the cell, repolarizing and then hyperpolarizing the membrane. K+K+ K+K+ K+K+ Na + + - 22

23. Repolarization 23

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25. Action potentials: Resuming the Resting Potential Potassium channels close. Repolarization resets sodium ion channels. Ions diffuse away from the area. Sodium-potassium transporter maintains polarization. The membrane is now ready to “fire” again. K+K+ K+K+ K+K+ K+K+ Na + K+ Na+ K+ 25

26. The Action Potential The action potential is “all-or-none”. It is always the same size. Either it is not triggered at all - e.g. too little depolarization, or the membrane is “refractory”; Or it is triggered completely. 26

27. Action Potential Local Currents depolarize adjacent channels causing depolarization and opening of adjacent Na channels Question: Why doesn’t the action potential travel backward? 27

28. Course of the Action Potential The action potential begins with a partial depolarization (e.g. from firing of another neuron ) [A]. When the excitation threshold is reached there is a sudden large depolarization [B]. This is followed rapidly by repolarization [C] and a brief hyperpolarization [D]. There is a refractory period immediately after the action potential where no depolarization can occur [E] Membrane potential (mV) [A] [B] [C] [D] excitation threshold Time (msec) -70 +40 0 0 1 2 3 [E][E] 28

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30. about the membrane axon membrane separates fluids that differ greatly in their content of Na+ ions and K+ ions. the exterior fluid is about 10 times richer in Na+ than in K+; the interior fluid has the opposite proportion the membrane is penetrated by proteins that act as selective channels for preferentially passing either Na+ or K+ 30

31. the resting state when no nerve impulse is being transmitted, the two types of channel are closed, and an ion pump maintains the ionic disequilibrium by pumping out Na+ and exchanging with K+. The interior of the cell is -70 meV with respect to the exterior 31

32. action potential If the voltage difference is reduced by the arrival of a nerve impulse, the Na+ ion channel opens, allowing Na+ ions to flow into the axon An instant later, the ion channel closes and the K+ channel opens, allowing an outflow of K+ ions 32

33. Conduction of the action potential Passive conduction will ensure that adjacent membrane depolarizes, so the action potential “travels” down the axon But transmission by continuous action potentials is relatively slow and energy-consuming (Na + /K + pump) A faster, more efficient mechanism has evolved: saltatory conduction Myelination provides saltatory conduction. 33

34. Myelination Most mammalian axons are myelinated. The myelin sheath is provided by oligodendrocytes and Schwann cells. Myelin is insulating, preventing passage of ions over the membrane. 34

35. Saltatory Conduction Myelinated regions of axon are electrically insulated. Electrical charge moves along the axon rather than across the membrane. Action potentials occur only at unmyelinated regions: nodes of Ranvier. Node of RanvierMyelin sheath 35

36. Synaptic transmission Information is transmitted from the presynaptic neuron to the postsynaptic cell. Chemical neurotransmitters cross the synapse, from the terminal to the dendrite or soma. The synapse is very narrow, so transmission is fast. 36

37. terminal dendritic spine synaptic cleft presynaptic membrane postsynaptic membrane extracellular fluid Structure of the synapse An action potential causes neurotransmitter release from the presynaptic membrane. Neurotransmitters diffuse across the synaptic cleft. They bind to receptors within the postsynaptic membrane, altering the membrane potential. 37

38. Neurotransmitter release Synaptic vesicles, containing neurotransmitter, congregate at the presynaptic membrane. The action potential causes voltage-gated calcium (Ca 2+ ) channels to open; Ca 2+ ions flood in. vesicles Ca 2+ 38

39. Neurotransmitter release Ca 2+ causes vesicle membrane to fuse with presynaptic membrane. Vesicle contents empty into cleft: exocytosis. Neurotransmitter diffuses across synaptic cleft. Ca 2+ 39

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41. Ionotropic receptors (ligand gated) Synaptic activity at ionotropic receptors is fast and brief (milliseconds). Acetylcholine (Ach) works in this way at nicotinic receptors. Neurotransmitter binding changes the receptor’s shape to open an ion channel directly. ACh 41

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43. Ionotropic Receptors 43

44. Metabotropic Receptors (G-Protein) 44

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46. Postsynaptic potentials Depending on the type of ion channel which opens, the postsynaptic cell membrane becomes either depolarized or hyperpolarized. Ions will tend to follow the concentration gradient from high to low concentration, and the electrostatic gradient towards the opposite charge. 46

47. Excitatory postsynaptic potentials (EPSPs) Opening of ion channels which leads to depolarization makes an action potential more likely, hence “excitatory PSPs”: EPSPs.  Inside of post-synaptic cell becomes less negative.  Na + channels  Ca 2+ inside outside Na + Ca 2+ + - 47 temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cellmembrane potentialions

48. Inhibitory postsynaptic potentials (IPSPs) Opening of ion channels which leads to hyperpolarization makes an action potential less likely, hence “inhibitory PSPs”: IPSPs.  Inside of post-synaptic cell becomes more negative.  K +  Cl - K+K+ Cl - + - inside outside 48

49. Postsynaptic Ion motion 49

50. Requirements at the synapse For the synapse to work properly, six basic events need to happen: Production of the Neurotransmitters  Synaptic vesicles (SV) Storage of Neurotransmitters  SV Release of Neurotransmitters Binding of Neurotransmitters  Lock and key Generation of a New Action Potential Removal of Neurotransmitters from the Synapse  reuptake 50

51. Integration of information PSPs are small. An individual EPSP will not produce enough depolarization to trigger an action potential. IPSPs will counteract the effect of EPSPs at the same neuron. Summation means the effect of many coincident IPSPs and EPSPs at one neuron. If there is sufficient depolarization at the axon hillock, an action potential will be triggered. axon hillock 51

52. Three Nobel Prize Winners on Synaptic Transmission Arvid Carlsson discovered dopamine is a neurotransmitter. Carlsson also found lack of dopamine in the brain of Parkinson patients. Paul Greengard studied in detail how neurotransmitters carry out their work in the neurons. Dopamine activated a certain protein (DARPP-32), which could change the function of many other proteins. Eric Kandel proved that learning and memory processes involve a change of form and function of the synapse, increasing its efficiency. This research was on a certain kind of snail, the Sea Slug (Aplysia). With its relatively low number of 20,000 neurons, this snail is suitable for neuron research. 52

53. Neuronal firing: the action potential The action potential is a rapid depolarization of the membrane. It starts at the axon hillock and passes quickly along the axon. The membrane is quickly repolarized to allow subsequent firing. 53