1. 1 Session 4 The Neuron PS111 Brain & Behaviour Module 1: Psychobiology

2. What are neurons good for? In complex organisms, cells... on the inside of the body are not in direct contact with the outside world... live in different ‘environments’... have become specialised In order for the organisms to function, cell activities must be co-ordinated Why do more complex organisms need a nervous system?

3. a) Endocrine system: specialised to secrete chemicals (‘hormones’) into the bloodstream provide slow, overall co-ordination of cell activities Two systems to co-ordinate cell activities: b) Nervous system: specialised to transmit electrical impulses between two or more cells provide fast and precise co-ordination What are neurons good for?

4. Hi, Mike!

5. What are neurons good for? Hi, Mike!

6. QUESTIONS: How are neural impulses generated? How are they transmitted? What is their function? What are neurons good for? Neural impulses (‘signals’) provide constant & rapid communication between cells. Signals from one (group of) cells change properties of receiving cell => i.e., change the way the receiving cell ‘behaves’ In other words: Neural impulses provide constant & rapid control & adjustment of ongoing cell activities

7. 1. Function: Generation & transmission of electrical impulses Neurons are special! Electrical impulses reach specific targets Modifies activity of the target cells Allows selective control of specific target structures Electrical activity modulated by integrated input from other cells ‘Input’ used to adjust ‘output’ Combination & integration of signals from different sources Structured communication Rapid Over great distances Point-to-point

8. Smooth muscle cellSkin cells Ovary cellBlood cells Neural (pyramidal) cell 2. Form & Size: Neurons are special!

9. Glucose (sugar) & oxygen must be constantly supplied Without supply, neurons stop working within seconds die within minutes 4. Life span: Neurons do not divide (they develop from ‘neural stem cells’) Neurogenesis virtually completed around 5 months after conception: after this, dead neurons can not be replaced (mostly) Neuron death part of normal brain development: 20% to 80% of all neurons die during maturation because neurons are so special… 3. Special requirements: Virtually no possibility to store energy Neurons are special!

10. l Provide ‘protected environment’ for neurons to survive l Develop – like neurons – from neural stem cells l About 10 times as many glia as neurons, l on average 1/10 the size of a neuron Glia Cells

11. 11 star-shaped physical & nutritional support for neu- rons (part of Blood-Brain-Barrier): transport nutrients from blood vessels to neurons and waste products away from neurons hold neurons in place Play a role in neural signal transmission as well! small mobile for defensive function: produce chemicals that aid repair of damaged neurons digest dead neurons (phagocytosis) Glia Cells Astrocytes: Microglia: http:// i.livescience.com/images/060105_astrocyte_02.jpg Xu, Pan, Yan, & Gan, NatNeuro,10, 549-551. http://www.nature.com/neuro/journal/v10/n5/images/nn1883-F2.jpg

12. large, flat branches wrapped around axons consist of fatty sub- stance (myelin) insulating the axon Other types of glia exist, but will not be discussed here... Oligodendroglia: Glia Cells

13. Neurons

14. 14 Neurons Axon Axon Hillock Axon terminals Soma Dendrites Neural Signal Transmission... Membrane

15. Neurons are not empty, and do not exist in a vacuum: Thick chemical ‘soup’ of electrically charged particles fills the neuron (‘intra-cellular fluid’) surrounds the neuron (‘extra-cellular fluid’) (now recall that the membrane has holes) Positively charged ions Negatively charged ions

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32. HOW??

33. 1. Basic principles: Electrical activity - Resting potential Concentration Gradient Electrical Gradient Cl

34. K + Na + Cl - A - K + A - + - Na + Cl - K + Na + Cl - Concentration Gradient Electrical Gradient Protein channels in cell membrane allow ions to enter or leave the cell: Electrical potential remains static => no electrical activity 2. Ion gradients: Electrical activity - Resting potential K + Na + Cl - - - A - K + A - Na + Cl - K + Na + Cl - + - (-70 mV) Ion concentrations differ between the inside and the outside of the cell:

35. K + Na + Cl - A - K + A - Na + Cl - K + Na + Cl - Active channels work against the equilibrium: + - (-70 mV) 3. Sodium/potassium pump and membrane potential: Na + K + Neurons need energy just to maintain their resting potential! If channels were passive ‘holes’, membrane would depolarise (electrical potential would disappear): Again, there would be no electrical activity! K + Na + Cl - A - Na + A - K + Cl - 0 0 K+K+ Na + Cl - 2. Ion gradients: Electrical activity - Resting potential

36. Based on movement of electrically charged particles (ions): Ion-specific channels in cell membrane are GATES that can open (they are not open all the time!) either by chance or in response to stimulation Positive or negative ions enter or leave the cell Depolarisation: Positive ions in, or negative ions out: Inside less negative than usually Hyperpolarisation: Negative ions in, or positive ions out: Inside more negative than usually Electrical activity – Signal Transmission

37. ElectrotonicAction Potential Synaptic Passive: Ions move inside the cell along electrical & concentra- tion gradients. Some ions will get lost on their way: Signal decays over time Electrical activity – Signal Transmission

38. ElectrotonicAction Potential Synaptic Active (self-replicating, no decay): ions move locally through cell membrane. Generated at axon hillock, moves down the axon towards ter- minal buttons Electrical activity – Signal Transmission

39. Sequence of events: 1. Membrane depolarised (inside less negative) 5. All nearby Na + channels open 4. Membrane depolarises further -- THRESHOLD? 3. Na + ions enter the cell 2. Some Na + channels open 6. Membrane fully depolarised (more positive on the in- than on the outside!) K + Na + Cl - A - A - K + Cl - K+K+ NaCl - + - (-70 mV) Na + K + Resting potential: Na + K + Na + Cl - A - A - K + Cl - K+K+ NaCl - (-70 mV) Na + K + Electrical stimulation: Na + + 1. Voltage gated membrane channels: Na + channels open or close in response to electrical changes at the membrane K + Na + Cl - A - A - K + Cl - K+K+ NaCl - (-50 mV) Na + K + Na + inflow: Na + K + Na + Cl - A - A - K + Cl - K+K+ NaCl - (-50 mV) Na + K + Na + Threshold: Na + K + Na + Cl - A - A - K + Cl - K+K+ NaCl - (+50 mV) Na + K + Na + Electrical activity – Action Potential

40. 2. Threshold potential and the Hodgkin-Huxley cycle: If membrane depolarises further: more and more Na + channels will open, resulting in more and more depolarisation Na + inflowNa + channels open Membrane depolarises Electrical stimulation If membrane potential at axon hilock reaches threshold: all Na + channels in depolarised area open simultaneously, generating an action potential If membrane potential at axon hillock remains below threshold, resting potential returns Electrical activity – Action Potential

41. Threshold has been reached: so many Na + ions enter the cell that inside becomes more positive than outside (complete depolarisation) Na + channel open Na + IN 3. Electrochemical processes during an AP Complete depolarisation causes a) Closing of Na + channels: No more Na + ions enter cell b) Opening of K + channels: K + ions rush out of cell: membrane repolarises Na + channel close, K + channel open K + OUT K + channels close when resting potential is restored briefly, less K + ions inside than outside cell: membrane hyperpolarized (inside more negative than usual) Electrical activity – Action Potential

42. 4. Conduction of the action potential Originates at axon hillock & travels down the axon Each burst of depolarisation acts as a trigger, opening Na + channels in adjacent regions of the axon Why does the action potential not travel backwards? Electrical activity – Action Potential During hyperpolarisation, mem- brane more difficult to depo- larise But adjacent part of axon (where AP has not yet occurred) easy to depolarise

43. Electrical activity – Action Potential 5. Properties of the action potential: No decay: always strong enough to depolarise adjacent membrane ‘All-or-nothing’ phenomenon: either generated or not can not be generated with different intensities! Discontinuous: minimal time between subsequent APs: 2-5ms Fast: approx. 1-10 m/s l However, for some purposes, this might not be fast enough

44. In mammals, the axons of sensory and motor neurons are myelinated Electrical charges transported inside the axon no need to produce an AP Myelin insulates, preventing ion inflow and outflow 6. Saltatory conduction Electrical activity – Action Potential

45. Axon + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + ++++ + + + + + + + + + + + +++ + Myelin + + + + + + + + + + ++++ + + + + + + + + + + ++++ In mammals, the axons of sensory and motor neurons are myelinated Nodes of Ranvier: gaps that interrupt insulation every 1-2 mm Electrical charges transported inside the axon no need to produce an AP Myelin insulates, preventing ion inflow and outflow 6. Saltatory conduction Electrical activity – Action Potential Node of Ranvier

46. + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + ++++ + + + + + + + + + + + +++ + + + + + + + + + + + ++++ + + + + + + + + + + ++++ In mammals, the axons of sensory and motor neurons are myelinated Nodes of Ranvier: gaps that interrupt insulation every 1-2 mm Electrical charges transported inside the axon no need to produce an AP Myelin insulates, preventing ion inflow and outflow 6. Saltatory conduction Electrical activity – Action Potential

47. 7. Signal transmission and information: Electrical impulses can not be modified! How are different types of information ‘coded’? Qualitative: by location the place in the brain where the signal is received (cf. last lecture) Quantitative (how strong a stimulus is): by ‘firing rate’ a strong input causes a neuron to send out APs in quicker succession Electrical activity – Action Potential time voltage Weak stimulus: time voltage Strong stimulus:

48. ElectrotonicAction Potential Synaptic Signal Transmission (details in the next lecture…)

49. QUESTION TIME

50. 1. In the figure below, the number 3 indicates the a) pons b) thalamus c) corpus callosum d) limbic system e) cerebellum 2 1 3 4 5

51. QUESTION TIME 2. Relative to its environment, the neuron during its resting state is ___ charged; depolarisation means that it becomes more ___ than during resting state, hyperpolarisation means that it becomes more ___ than during resting state a) Negatively; negative; positive b) Positively; negative; positive c) Negatively; positive; negative d) Positively; positive; negative e) Neutrally; negative; positive

52. QUESTION TIME 3. The function of myelin is to a) Form part of the blood-brain barrier b) Remove waste products from neurons c) Provide structural stability and support d) Electrically insulate axons e) Participate in synaptic signalling

53. QUESTION TIME 4. Which of the following is NOT a function of microglia? a) Remove waste products from neurons b) Provide structural stability and support c) Electrically insulate axons d) Participate in synaptic signalling e) None of these is a function of microglia

54. QUESTION TIME 5. Correctly label the parts in Figure 1: a) 1. Axon terminals; 2. Axon; 3. Soma; 4. Dendrites b) 1. Nodes of Ranvier; 2. Dendrite; 3. Soma; 4. Axon terminals c) 1. Axons; 2. Dendrite; 3. Axon hillock; 4. Myelin d) 1. Dendrites; 2. Axon; 3. Axon hillock; 4. Spines e) 1. Nodes of Ranvier; 2. Myelin; 3. Cell body; 4. Dendrites

55. QUESTION TIME 6. The direction of signal transmission in the neural network shown in Figure 2 is a) From A to B and C b) From C to A and B c) From B to A to C d) From A and B to C e) From C and B to A

56. QUESTION TIME 7. Signals from the ears enter the forebrain at the a) 1 – pons b) 2 – thalamus c) 3 – corpus callosum d) 4 – occipital lobe e) 5 - cerebellum 2 1 3 4 5

57. QUESTION TIME 8. Damage to which structures might cause blindness? a) 1 & 2 b) 1 & 5 c) 2 & 4 d) 1, 2, & 3 e) 4 & 5 2 1 3 4 5