Molecular biology of neural communication

Transcription

1 Molecular biology of neural communication

2 One picture - two information

3 Where do I feel the pain?

4 Real and Virtual Consciousness Almost all neural process is pervaded by the consciousness We not only perceive the incoming information, but also interpret and subjectively experience them Consciousness produces a virtual world, which is believed to be real

5 0 Hierarchy of neural processing Neuron neural centers neural networks consciousness

6 Structure of the talk 1. Introduction 2. Operation of a neuron 3. Communication between neurons

7 Introduction

8 1a Local and distant communication between animal cells

9 1b Modes of signal transmission Hormone system Nervous system

10 2 The reticular - versus neuron doctrine Nobel Price: 1906 Camillo Golgi Santiago Ramón y Cajal

11 3 Complexity of nervous system Human brain Number of neurons: 3-5 x Number of synapses/neuron: 10 4 Total number of synapses: 3-5 x Synaptic plasticity The response of a neuron to a stimulus depends on its internal state, which under a complicated control

12 4 Types of neurons Interneurons sensory neuron motor neuron local projection

13 Operation of a neuron a. Resting potential b. Transport proteins c. Action potential

14 Resting potential

15 5 Migration of charged particles Lower concentration Passive Active Induced by 3 factors: 1. Concentration gradient 2. Electrical gradient 3. Ion pump Higher concentration Positive side Negatíve side

16 6 Donnan equilibrium Outer space Semipermeable membrane Inner space

17 7 Steady state for K-ions (dynamic constancy) A hypothetical cell: only can freely move Initial state CELL EXTERIER

18 8 Steady state for (dynamic constancy) A hypothetical cell: only can freely move Steady state CELL EXTERIER

19 9 Equillibrium potential - steady state for

20 10 Resting potential Definition: The resting potential is the voltage across the plasma membrane of an excitable unstimulated cell.

21 11 Resting potential Plasma membrane Voltmeter 70 mv Microelectrode outside the cell Microelectrode inside the cell Axon Neuron

22 Transport proteins

23 12 Types of transport proteins A. Ion channels passive transport I. Specific channels -, Na +, Ca 2+, Cl - II. Cation-selective channels B. Ion pumps active transport

24 12 Types of transport proteins A. Ion channels passive transport I. Leaky channels - nonregulated II. Gated channels - regulated - Voltage-gated channels - Ligand-gated channels - Phosphorylation-gated channels - Stretch-gated channels - Gap junction channels B. Ion pumps active transport

25 13 Gated ion channels Ligand-gated Voltage-gated Phosphorylation-gated Gate Stretch/pressure-gated

26 14 Gap junctions Gap junction

27 15 Na + - -pump Extracellular space ATP Cytoplasm Na + Na + High K+ permeability Na + Na + Na + Na + Na + Na + Na + Low Na+ permeability Na + Na +

28 16 Na + /Ca + -channels Channel pore S1 S2 S3 S4 S5 S6 H5 S4 segment: voltage sensor -subunit

29 17 Na + -channel

30 18 -channels Channel pore S1 S2 S3 S4 S5 S6 H5 S4 segment: voltage sensor

31 19 Extended -channel family Depolarization-activated, non-inactivating channel Depolarization-activated, inactivating channel Depolarization- and Ca 2+ - activated channel Cyclic nucleotid-activated cation channel Inward rectifier channel

32 20 Operation of voltage-gated ion channels Activation gate Inactivation gate

33 21 Operation of voltage sensors Na + Na + Na + Na + Na + Na + Voltage sensors Activation gate

34 Action potential

35 22 Excitation, EPSP EPSP: excitatory post-synaptic potential

36 23 Inhibition, IPSP EPSP: excitatory post-synaptic potential IPSP: inhibitory post-synaptic potential

37 24 Excitation, inhibition IPSP EPSP Action potential IPSP EPSP

38 25 Excitation - inhibition Na + Na + Cl - Cl - Cl - Cl - Outer space Na + Na Cell membrane Depolarization Intracellular millieu

39 26 Excitation - inhibition Na + Na + Cl - Cl - Cl - Cl - Outer space Na + Na Cell membrane Hiperpolarization Intracellular millieu

40 27 Sapatio-temporal summation Spatial summation Temporal summation

41 28 The all-or-none principle IPSP EPSP Action potential IPSP EPSP

42 29 Progression of action potential Axon Action potential 1 Na + Axon segment Action potential 2 Na + Action potential 3 Na +

43 30 Progression of action potential 3 Na + 4 Further Na + channels open, the channels are still closed 2 Na + Na+ Action potential Axon hillock 3 The Na + channels become closed, the channels open Na+ A stimulus can open some Na+ channels; if it exceeds the threshold: action potential will be generated 2 Threshold potential 1 Resting potential The channels slowly become closed: short undershoot 1 Axon 6 Return to resting state Resting state: voltage-gated Na + and channels are closed

44 31 Progression of action potential Resting state Depolarization Repolarization Undershoot

45 32 Progression of action potential

46 33 Saltatory conduction

47 34 Travelling signals

48 Communication between neurons a. Synaptic signal transmission b. Receptors c. Signal transduction in neurons d. Neuromodulation

49 Synaptic signal transmission

50 35 Traveling signals

51 36 Imputs of a neuron Dendrites Synaptic nodes Myelin sheath Axon Receiving cell body Synaptic nodes

52 37 Types of synapses-i Electric synapses Chemical synapses

53 38 Types of synapses-ii

54 39 SENDING NEURON Vesicles Synaptic knob 1 Action potential arrives 2 3 Vesicle fuses with plasma membrane 4 Neurotransmitter is released into synaptic cleft Ca ++ Operation of synapses 5 Ca + enter the cells SYNAPTIC CLEFT RECEIVING NEURON Ion channels Ions Neurotransmitter Receptor Neurotransmitter molecules Neurotransmitter binds to receptor Neurotransmitter broken down and released 6 Ion channel opens 7 Ion channel closes

55 40 Neurotransmitters I. Biogen amines Histamin Serotonin Dopamine Norepinephrine catecholamines Adrenaline Monoamines II. Aminoacids Glutamate, aspartate, glicine, GABA III. Peptides Substance P, enkephalins, endorphins, angiotensin, somatostatin, vasopressin IV. Acetylcholin V. Other transmitters NO, CO, ATP, H +

56 Receptors

57 41 Types of receptors Metabotropic receptors Ionotropic receptors - Direct gating of ion flow - Indirect gating of ion flow - Fast effect - Slow effect

58 42 Types of receptors N + N + N + N +

59 43 Ionotropic receptors: ligand-gated ion channel receptors Nicotinic receptor Glutamate receptor ATP receptor superfamily superfamily superfamily 4 segmenst 3 segments 2 segments P2X and ASIC receptors 5 subunits 4 subunits 3 subunits

60 44 G protein-coupled receptors - metabotropic receptors

61 Signal transduction in neurons

62 Nobel Díj: 2000 Nobel Prize signal transduction in the nervous system Arvid Carlsson Paul Greengard Eric R. Kandel

63 45 Signal transduction in neurons

64 46 Signal transduction in neurons

65 GDP 47 Adenylyl cyclase second messenger system Metabotropic receptor Adenylyl cyclase Ion channel R CELL MEMBRANE AC I C G s protein PK Protein kinase A

66 GDP GTP 47 Adenylyl cyclase second messenger system Metabotropic receptor Adenylyl cyclase Ion channel R CELL MEMBRANE AC I C PK Protein kinase A

67 GDP GTP 47 Adenylyl cyclase second messenger system Metabotropic receptor Adenylyl cyclase Ion channel R CELL MEMBRANE cam P AC I C P AT P cam P PK Protein kinase A

68 GTP 47 Adenylyl cyclase second messenger system Metabotropic receptor Adenylyl cyclase Ion channel CELL MEMBRANE R AC I C P cam P Protein kinase A PK

69 GDP GTP 47 Adenylyl cyclase second messenger system Metabotropic receptor Adenylyl cyclase Ion channel CELL MEMBRANE R AC I C

70 GDP 48 Phosphoinositide second messenger system Metabotropic receptor Phospholipase C Potasium ionchannel R CELL MEMBRANE PIP2 Protein kinase C DAG PK P I C Calmodulin kinase II CaMKII G q protein K+ CaM P ER IP3 IP3 receptor Ca 2+ CaM Ca 2+ PIP2:phosphatidyl inositol-4,5-biphsophate IP3: inositol-1,4,5-triphosphate DAG: diacylglycerol CaM: calmodulin

71 49 Signal transduction cascade

72 Neuro-modulation

73 50 Inhibition A on presynaptic neuron Inhibition of transmitter release a variety of mechanisms B on postsynaptic neuron i.p.s.p

74 51 Auto-receptors Pre-synaptic neuron Ionotropic receptor Ionotropic receptor Post-synaptic neuron

75 52 Metabotropic receptor modulation

76 53 Neurotransmitter deactivation Antidepressants: Selective serotonin reuptake inhibitors (SSRIs) 1. Reuptake Neurotransmitter reuptake pump Monoamino oxidase (MAO) inhibitors Acetylcholin estherase 2. Inactivating enzymes 3. diffusion

77 Long term potential

78 54 Hippocampus Thalamus CEREBRUM Hypothalamus Prefrontal cortex Olfactory bulb Amygdala Hippocampus

79 55 Hippocampus

80 56 Long-term potential (LTP) Schaffer collateral CA1 NMDA, non-nmda: ionotropic glutamate receptors

81 57 LTP Schaffer collateral CA1

82 58 LTP Schaffer collateral CA1 CRE: camp response element CREB: CAMP response element binding protein

83 59 LTP Schaffer collateral

84 60 Functional neural systems Peripheral nervous system Central nervous system Somatic nervous system Somatosensory systems Motor systems Associative systems Autonomic nervous system Sympathetic nevous system Parasympathetic nervous system Enteral nervous system