1. EE141 1 Brain Structures [Adapted from Neural Basis of Thought and Language Jerome Feldman, Spring 2007, feldman@icsi.berkeley.edu Broca’s area Pars opercularis Motor cortexSomatosensory cortex Sensory associative cortex Primary Auditory cortex Wernicke’s area Visual associative cortex Visual cortex

2. EE141 2 Intelligence Learning and Understanding I hear and I forget I see and I remember I do and I understand attributed to Confucius 551-479 B.C. There is no erasing in the brain

3. EE141 3 Intelligence and Neural Computation  What it means for the brain to compute and how that computation differs from the operation of a standard digital computer.  How intelligence can be implemented in the structure of the neural circuitry of the brain.  How is thought related to perception, motor control, and our other neural systems, including social cognition?  How do the computational properties of neural systems and the specific neural structures of the human brain shape the nature of thought?  What are the applications of neural computing?

4. EE141 4 Nervous System Divisions  Central nervous system (CNS)  brain  spinal cord

5. EE141 5 Nervous System Divisions  Peripheral nervous system (PNS) consists of:  Cranial and spinal nerves  Ganglia  Sensory receptors  Subdivided into:  Somatic  Autonomic –Motor component subdivided into: l sympathetic l parasympathetic  Enteric

6. EE141 6 Brains ~ Computers  1000 operations/sec  100,000,000,000 units  10,000 connections/  graded, stochastic  embodied  fault tolerant  evolves  learns  1,000,000,000 ops/sec  1-100 processors  ~ 4 connections  binary, deterministic  abstract  crashes  designed  programmed

7. EE141 7 PET scan of blood flow for 4 word tasks

8. EE141 8 Neurons structures

9. EE141 9 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

10. EE141 10 Neuron cells  unipolar  bipolar  multipolar

11. EE141 11 Synapse  site of communication between two cells  formed when an axon of a presynaptic cell “connects” with the dendrites of a postsynaptic cell science-education.nih.gov

12. EE141 12 Synapse axon of presynaptic neuron dendrite of postsynaptic neuron bipolar.about.com/library

13. EE141 13 Synapse a synapse can be excitatory or inhibitory depolarizesarrival of activity at an excitatory synapse depolarizes the local membrane potential of the postsynaptic cell and makes the cell more prone to firing hyperpolarizes 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

14. EE141 14 Visual cortex of the rat

16. EE141 16 Somatotopy of Action Observation Foot Action Hand Action Mouth Action Buccino et al. Eur J Neurosci 2001

17. EE141 17 How does it all work?

18. EE141 18 Artist’s rendition of a typical cell membrane Amoeba eating

19. EE141 19 From lecture notes by Dr Rachel Swainson NEURAL COMMUNICATION 1: Transmission within a cell and from a lecture notes based on www.unisanet.unisa.edu.au/Information/12924info/Lecture Presentation - Nervous tissue.ppt Neural Processing

20. EE141 20 Transmission of information Information must be transmitted  within each neuron  and between neurons

21. EE141 21 The Membrane  The membrane surrounds the neuron.  It is composed of lipid and protein.

22. EE141 22 Artist’s rendition of a typical cell membrane

23. EE141 23 Cell Electrical Potential Cell Electrical Potential Every neuron is covered by a membrane The membrane is selectively permeable to the passage of chemical molecules (ions) The membrane maintains a separation of electrical charge across the cell membrane. The cell membrane has an electrical potential Electrical potentials Electrical charge of the membrane is related to charged ion that cross the membrane through lipids, ion channels and protein ion-transporters. Electrical currents (ionic flux) The flow of electrical charge between the cell’s interior and exterior cellular fluids

24. EE141 24 Forces determine flux of ions Forces determine flux of ions –Electrostatic forces Particles with opposite charges attract, Identical charges repel –Concentration forces Diffusion – molecules distribute themselves evenly – –Protein – ion channels Selective Non – gated ion channels Selective Voltage-dependent gated ion channels –Protein – ion transporters –K+ Na + pump Cl - pump

25. EE141 25 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 + - + - + - + - + -

26. EE141 26 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 (-)

27. EE141 27 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 +

28. EE141 28 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.

29. EE141 29 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].

30. EE141 30 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.

31. EE141 31 Action potential 2 phases:  Depolarisation –graded potentials move toward firing threshold –if reach threshold voltage regulated sodium channels open –reversal of membrane permeability  Repolarisation –sodium channels close –potassium channels open

32. EE141 32 Before Depolarization

33. EE141 33 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 + - + + -

34. EE141 34 Depolarization

35. EE141 35 Depolarization

36. EE141 36 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 + + -

37. EE141 37 Repolarization

38. EE141 38 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+

39. EE141 39 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.

40. EE141 40 Action Potential

41. EE141 41 Propagation of the Action Potential Action Potential spreads down the axon in a chain reaction Unidirectional –it does not spread into the cell body and dendrite due to absence of voltage-gated channels there –Refraction prevents spread back across axon

42. EE141 42 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.

43. EE141 43 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

44. EE141 44 Summary of axonal conduction  Unmyelinated fibres  continuous conduction  Myelinated fibres  saltatory conduction –High density of voltage gated channels at Nodes of Ranvier  Larger diameter axons propagate impulses faster  Stimulus intensity encoded by:  frequency of impulse generation  number of sensory neurons activated

45. EE141 45 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.

46. EE141 46 terminal dendritic spine synaptic cleft presynaptic membrane postsynaptic membrane extracellular fluid Structure of a 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.

47. EE141 47 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+

48. EE141 48 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+

49. EE141 49

50. EE141 50 Opening and closing of the channel in synaptic membrane

51. EE141 51 Ionotropic receptors  Synaptic activity at ionotropic receptors is fast and brief (milliseconds).  Acetyl choline (Ach) works in this way at nicotinic receptors.  Neurotransmitter binding changes the receptor’s shape to open an ion channel directly. ACh

52. EE141 52 Ionotropic Receptors 4 nm

53. EE141 53 Metabotropic Receptors (G-Protein)

54. EE141 54 Postsynaptic Ion motion

55. EE141 55 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.

56. EE141 56 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 (remember the action potential)  Ca 2+. (Also activates structural intracellular changes -> learning.) inside outside Na + Ca 2+ + -

57. EE141 57 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 + (remember termination of the action potential)  Cl - (if already depolarized) K+K+ Cl - + - inside outside

58. EE141 58 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

59. EE141 59 Requirements at the synapse For the synapse to work properly, six basic events need to happen: 1. Production of the Neurotransmitters 2. Storage of Neurotransmitters 3. Release of Neurotransmitters 4. Binding of Neurotransmitters 5. Generation of a New Action Potential 6. Removal of Neurotransmitters from the Synapse

60. EE141 60 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) that has relatively low number of neurons (20,000 ).

61. EE141 61 Neural circuits  Divergence  Single presynaptic neuron synapses with several postsynaptic neurons –Example: sensory signals spread in diverging circuits to several regions of the brain  Convergence  Several presynaptic neurons synpase with single postsynaptic neuron –Example: single motor neuron synapsing with skeletal muscle fibre receives input from several pathways originating in different brain regions

62. EE141 62 Neural circuits  Pulsing circuit  Once presynaptic cell stimulated causes postsynaptic cell to transmit a series of impulses –Example: coordinated muscular activity  Parallel after-discharge circuit  Single presynaptic neuron synapses with multiple neurons which synapse with single postsynaptic cell –results in final neuron exhibiting multiple postsynaptic potentials l Example: may be involved in precise activities (eg mathematical calculations)

63. EE141 63