1. An Introduction to Neurotransmission William Wisden Dept of Clinical Neurobiology INF 364 William.Wisden@urz.uni-heidelberg.de

2. Fundamental Neuroscience - second edition Squire, Bloom, McConnell, Roberts, Spitzer, Zigmond Academic Press, 2003 http://faculty.washington.edu/chudler/neurok.html http://faculty.washington.edu/chudler/chnt1.html Explore the Brain and Spinal Cord The Neuron http://www.indstate.edu/thcme/mwking/home.html http://www.indstate.edu/thcme/mwking/nerves.html

3. A neuron

4. The action potential

5. Hodgkin & Huxley, 1939

6. Rate of action potential firing is information

7. The dendrite

9. Differences between axons and dendrites AxonsDendrites Take information away from the cell body Bring information to the cell body Smooth Surface Rough Surface (dendritic spines) Generally only 1 axon per cell Usually many dendrites per cell No ribosomes Have ribosomes Can have myelin No myelin insulation Branch further from the cell bodyBranch near the cell body

10. Dendrites constitute a kind of neural microchip for complex computations

12. Rate of action potential firing is information Frequency code of impulses within the axons Place/topological code depending on which axons are active

16. Chemical synapse Axon-dendriteAxo-axonicAxon-soma

17. Passing information between neurons Gap junctions -electrical transmission fast both directions Chemical transmission slower - unidirectional integrative amplifies and regenerates the signal

18. The synapse

19. IN OUT Calcium entry is excitatory Calcium is a second messenger which binds to target proteins e.g. Calmodulin

20. Axon Terminal Spine Dendrite Action potential Ca2+ Diffusion of Neurotransmitters Across the Synaptic Cleft Neurotransmitter Mobilization and Release Electrical Trigger for Neurotransmission

21. Ca2+ Action potential Depolarization

22. Electrical properties

23. How is the action potential generated? http://faculty.washington.edu/chudler/ap.html

26. EXCITATORY + INHIBITORY - IN OUT

28. Look at the animation! http://faculty.washington.edu/chudler/ap.html

29. Neurotransmitters

30. Excitatory Inhibitory Excitatory

31. Simple transmitters:  -aminobutyric acid (GABA) glutamic acid (glutamate) acetylcholine (Ach)

32. OUT IN Acetylcholine receptor Cl - GABA A receptor GABAGABA Inhibition Na + Glutamate/AMPA receptor G lu Excitation Na + AChACh

33. Neurons and glial cells

35. The process of chemical neurotransmission can be divided into five steps 1. Synthesis of the neurotransmitter in the presynaptic neuron 2. Storage of the neurotransmitter and/or its precursor in the presynaptic nerve terminal 3. Release of the neurotransmitter into the synaptic cleft 4. Binding and recognition of the neurotransmitter by target receptors 5. Termination of the action of the released transmitter

36. Life cycle of a neurotransmitter

37. An excitatory (glutamatergic) synapse

38. A synapse using  -aminobutyric acid (GABA)

40. A synapse that uses acetylcholine (ACh)

41. Simple circuits

42. Feed-forward inhibition

44. Negative feedback Feedback inhibition

45. Neocortex Interneuron - uses GABA Pyramidal neuron - uses glutamate

46. Ionotropic and metabotropic receptors Fast Ion flow in/out milliseconds Slow Second messenger cascades seconds

48. Ionotropic Metabotropic

49. OUT IN Cl - Na + GABA A receptorGlutamate/AMPA receptor GABAGABA G lu Inhibition Excitation

54. Neuromodulators Slow synaptic transmission