Cellular and Molecular Neurophysiology (eBook)

Front cover 1
Cellular and molecular neurophysiology 4
Copyright page 5
Contents 6
List of contributors 8
Foreword 10
Acknowledgements 11
Chapter 1 Neurons 12
1.1 NEURONS HAVE A CELL BODY FROM WHICH EMERGE TWO TYPES OF PROCESSES: THE DENDRITES AND THE AXON 12
1.2 NEURONS ARE HIGHLY POLARIZED CELLS WITH A DIFFERENTIAL DISTRIBUTION OF ORGANELLES AND PROTEINS 16
1.3 AXONAL TRANSPORT ALLOWS BIDIRECTIONAL COMMUNICATION BETWEEN THE CELL BODY AND THE AXON TERMINALS 20
1.4 NEURONS CONNECTED BY SYNAPSES FORM NETWORKS OR CIRCUITS 27
1.5 SUMMARY: THE NEURON IS AN EXCITABLE AND SECRETORY CELL PRESENTING AN EXTREME FUNCTIONAL REGIONALIZATION 30
FURTHER READING 30
Chapter 2 Neuron–glial cell cooperation 32
2.1 ASTROCYTES FORM A VAST CELLULAR NETWORK OR SYNCYTIUM BETWEEN NEURONS, BLOOD VESSELS AND THE SURFACE OF THE BRAIN 32
2.2 OLIGODENDROCYTES FORM THE MYELIN SHEATHS OF AXONS IN THE CENTRAL NERVOUS SYSTEM AND ALLOW THE CLUSTERING OF NA[sup(+)] CHANNELS AT NODES OF RANVIER 35
2.3 SCHWANN CELLS ARE THE GLIAL CELLS OF THE PERIPHERAL NERVOUS SYSTEM THEY FORM THE MYELIN SHEATH OF AXONS OR ENCAPSULATE NEURONS39
FURTHER READING 39
Chapter 3 Ionic gradients, membrane potential and ionic currents 40
3.1 THERE IS AN UNEQUAL DISTRIBUTION OF IONS ACROSS NEURONAL PLASMA MEMBRANE. THE NOTION OF CONCENTRATION GRADIENT 40
3.2 THERE IS A DIFFERENCE OF POTENTIAL BETWEEN THE TWO FACES OF THE MEMBRANE, CALLED MEMBRANE POTENTIAL (V[sub(m)]) 43
3.3 CONCENTRATION GRADIENTS AND MEMBRANE POTENTIAL DETERMINE THE DIRECTION OF THE PASSIVE MOVEMENTS OF IONS THROUGH IONIC CHANNELS: THE ELECTROCHEMICAL GRADIENT 44
3.4 THE PASSIVE DIFFUSION OF IONS THROUGH AN OPEN CHANNEL CREATES A CURRENT 45
3.5 A PARTICULAR MEMBRANE POTENTIAL, THE RESTING MEMBRANE POTENTIAL V[sub(rest)] 47
3.6 A SIMPLE EQUIVALENT ELECTRICAL CIRCUIT FOR THE MEMBRANE AT REST 49
3.7 HOW TO EXPERIMENTALLY CHANGE V[sub(rest)] 49
3.8 SUMMARY 51
APPENDIX 3.1 THE ACTIVE TRANSPORT OF IONS BY PUMPS AND TRANSPORTERS MAINTAIN THE UNEQUAL DISTRIBUTION OF IONS 51
APPENDIX 3.2 THE PASSIVE DIFFUSION OF IONS THROUGH AN OPEN CHANNEL 53
APPENDIX 3.3 THE NERNST EQUATION 54
Chapter 4 The voltage-gated channels of Na[sup(+)] action potentials 56
4.1 PROPERTIES OF ACTION POTENTIALS 56
4.2 THE DEPOLARIZATION PHASE OF Na[sup(+)]-DEPENDENT ACTION POTENTIALS RESULTS FROM THE TRANSIENT ENTRY OF Na[sup(+)] IONS THROUGH VOLTAGE-GATED Na[sup(+)] CHANNELS 58
4.3 THE REPOLARIZATION PHASE OF THE SODIUM-DEPENDENT ACTION POTENTIAL RESULTS FROM Na[sup(+)] CHANNEL INACTIVATION AND PARTLY FROM K[sup(+)] CHANNEL ACTIVATION 73
4.4 SODIUM-DEPENDENT ACTION POTENTIALS ARE INITIATED AT THE AXON INITIAL SEGMENT IN RESPONSE TO A MEMBRANE DEPOLARIZATION AND THEN ACTIVELY PROPAGATE ALONG THE AXON 78
FURTHER READING 84
APPENDIX 4.1 CURRENT CLAMP RECORDING 85
APPENDIX 4.2 VOLTAGE CLAMP RECORDING 86
APPENDIX 4.3 PATCH CLAMP RECORDING 87
Chapter 5 The voltage-gated channels of Ca[sup(2+)] action potentials: Generalization 94
5.1 PROPERTIES OF Ca[sup(2+)]-DEPENDENT ACTION POTENTIALS 94
5.2 THE TRANSIENT ENTRY OF Ca[sup(2+)] IONS THROUGH VOLTAGE-GATED Ca[sup(2+)] CHANNELS IS RESPONSIBLE FOR THE DEPOLARIZING PHASE OR THE PLATEAU PHASE OF… 95
5.3 THE REPOLARIZATION PHASE OF Ca[sup(2+)]-DEPENDENT ACTION POTENTIALS RESULTS FROM THE ACTIVATION OF K[sup(+)] CURRENTS I[sub(K)] AND I[sub(KCa)] 105
5.4 CALCIUM-DEPENDENT ACTION POTENTIALS ARE INITIATED IN AXON TERMINALS AND IN DENDRITES 108
5.5 A NOTE ON VOLTAGE-GATED CHANNELS AND ACTION POTENTIALS 110
FURTHER READING 111
APPENDIX 5.1 FLUORESCENCE MEASUREMENTS OF INTRACELLULAR Ca[sup(2+)] CONCENTRATION 113
FURTHER READING 120
APPENDIX 5.2 TAIL CURRENTS 120
FURTHER READING 121
Chapter 6 The chemical synapses 122
6.1 THE SYNAPTIC COMPLEX’S THREE COMPONENTS: PRESYNAPTIC ELEMENT, SYNAPTIC CLEFT AND POSTSYNAPTIC ELEMENT 123
6.2 THE INTERNEURONAL SYNAPSES 128
6.3 THE NEUROMUSCULAR JUNCTION IS THE GROUP OF SYNAPTIC CONTACTS BETWEEN THE TERMINAL ARBORIZATION OF A MOTOR AXON AND A STRIATED MUSCLE FIBRE 131
6.4 THE SYNAPSE BETWEEN THE VEGETATIVE POSTGANGLIONIC NEURON AND THE SMOOTH MUSCLE CELL 135
6.5 EXAMPLE OF A NEUROGLANDULAR SYNAPSE 136
6.6 SUMMARY 137
APPENDIX 6.1 NEUROTRANSMITTERS, AGONISTS AND ANTAGONISTS 138
APPENDIX 6.2 IDENTIFICATION AND LOCALIZATION OF NEUROTRANSMITTERS AND THEIR RECEPTORS 139
FURTHER READING 144
Chapter 7 Neurotransmitter release 145
7.1 OBSERVATIONS AND QUESTIONS 145
7.2 PRESYNAPTIC PROCESSES I: FROM PRESYNAPTIC SPIKE TO [Ca[sup(2+)]]i INCREASE 150
7.3 PRESYNAPTIC PROCESSES II: FROM [Ca[sup(2+)]] INCREASE TO SYNAPTIC VESICLE FUSION 156
7.4 PROCESSES IN THE SYNAPTIC CLEFT: FROM TRANSMITTER RELEASE IN THE CLEFT TO TRANSMITTER CLEARANCE FROM THE CLEFT 163
7.5 SUMMARY (Figures 7.16 and 7.17) 165
APPENDIX 7.1 QUANTAL NATURE OF NEUROTRANSMITTER RELEASE 167
APPENDIX 7.2 THE PROBABILISTIC NATURE OF NEUROTRANSMITTER RELEASE: THE NEUROMUSCULAR JUNCTION AS A MODEL 168
FURTHER READING 170
Chapter 8 The ionotropic nicotinic acetylcholine receptors 171
8.1 OBSERVATIONS 172
8.2 THE TORPEDO OR MUSCLE NICOTINIC RECEPTOR OF ACETYLCHOLINE IS A HETEROLOGOUS PENTAMER & #945
8.3 BINDING OF TWO ACETYLCHOLINE MOLECULES FAVOURS CONFORMATIONAL CHANGE OF THE PROTEIN TOWARDS THE OPEN STATE OF THE CATIONIC CHANNEL 177
8.4 THE NICOTINIC RECEPTOR DESENSITIZES 183
8.5 nACHR-MEDIATED SYNAPTIC TRANSMISSION AT THE NEUROMUSCULAR JUNCTION 185
8.6 NICOTINIC TRANSMISSION PHARMACOLOGY 189
8.7 SUMMARY 191
APPENDIX 8.1 THE NEURONAL NICOTINIC RECEPTORS 192
FURTHER READING 196
Chapter 9 The ionotropic GABA[sub(A)] receptor 197
9.1 OBSERVATIONS AND QUESTIONS 197
9.2 GABA[sub(A)] RECEPTORS ARE HETEROOLIGOMERIC PROTEINS WITH A STRUCTURAL HETEROGENEITY 197
9.3 BINDING OF TWO GABA MOLECULES LEADS TO A CONFORMATIONAL CHANGE OF THE GABA[sub(A)] RECEPTOR INTO AN OPEN STATE THE GABA[sub(A)] RECEPTOR DESENSITIZES200
9.4 PHARMACOLOGY OF THE GABA[sub(A)] RECEPTOR 205
9.5 GABA[sub(A)]-MEDIATED SYNAPTIC TRANSMISSION 211
9.6 SUMMARY 216
FURTHER READING 217
APPENDIX 9.1 MEAN OPEN TIME AND MEAN BURST DURATION OF THE GABA[sub(A)] SINGLE-CHANNEL CURRENT 217
APPENDIX 9.2 NON-INVASIVE MEASUREMENTS OF MEMBRANE POTENTIAL AND OF THE REVERSAL POTENTIAL OF THE GABA[sub(A)] CURRENT USING CELL-ATTACHED RECORDINGS OF SINGLE CHANNELS 217
Chapter 10 The ionotropic glutamate receptors 220
10.1 THERE ARE THREE DIFFERENT TYPES OF IONOTROPIC GLUTAMATE RECEPTORS. THEY HAVE A COMMON STRUCTURE AND ALL PARTICIPATE IN FAST GLUTAMATERGIC SYNAPTIC TRANSMISSION 220
10.2 AMPA RECEPTORS ARE AN ENSEMBLE OF CATIONIC RECEPTOR-CHANNELS WITH DIFFERENT PERMEABILITIES TO Ca[sup(2+)] IONS 224
10.3 KAINATE RECEPTORS ARE AN ENSEMBLE OF CATIONIC RECEPTOR-CHANNELS WITH DIFFERENT PERMEABILITIES TO Ca[sup(2+)] IONS 226
10.4 NMDA RECEPTORS ARE CATIONIC RECEPTOR-CHANNELS HIGHLY PERMEABLE TO Ca[sup(2+)] IONS THEY ARE BLOCKED BY Mg[sup(2+)] IONS AT VOLTAGES CLOSE TO THE RESTING POTENTIAL…230
10.5 SYNAPTIC RESPONSES TO GLUTAMATE ARE MEDIATED BY NMDA AND NON-NMDA RECEPTORS 237
10.6 SUMMARY 241
FURTHER READING 242
Chapter 11 The metabotropic GABA[sub(B)] receptors 243
11.1 GABA[sub(B)] RECEPTORS WERE ORIGINALLY DISCOVERED BECAUSE OF THEIR INSENSITIVITY TO BICUCULLINE AND THEIR SENSITIVITY TO BACLOFEN 243
11.2 STRUCTURE OF THE GABA[sub(B)] RECEPTOR 244
11.3 SUMMARY 250
11.4 GABA[sub(B)] RECEPTORS ARE G-PROTEIN-COUPLED TO A VARIETY OF DIFFERENT EFFECTOR MECHANISMS 250
11.5 SUMMARY 261
11.6 THE FUNCTIONAL ROLE OF GABA[sub(B)] RECEPTORS IN SYNAPTIC ACTIVITY 262
11.7 SUMMARY 266
FURTHER READING 266
Chapter 12 The metabotropic glutamate receptors 267
12.1 THE IDENTIFICATION OF THE EIGHT METABOTROPIC GLUTAMATE RECEPTOR SUBTYPES 268
12.2 HOW DO METABOTROPIC GLUTAMATE RECEPTORS CARRY OUT THEIR FUNCTION? STRUCTURE-FUNCTION STUDIES OF METABOTROPIC GLUTAMATE RECEPTORS 268
12.3 HOW TO IDENTIFY SELECTIVE COMPOUNDS ACTING AT METABOTROPIC GLUTAMATE RECEPTOR? – TOWARDS THE DEVELOPMENT OF NEW THERAPEUTIC DRUGS 271
12.4 WHAT BIOCHEMICAL MEANS DO METABOTROPIC GLUTAMATE RECEPTORS UTILIZE TO ELICIT PHYSIOLOGICAL CHANGES IN THE NERVOUS SYSTEM? – SIGNAL TRANSDUCTION STUDIES OF… 272
12.5 HOW IS THE ACTIVITY OF METABOTROPIC GLUTAMATE RECEPTORS MODULATED? – STUDIES OF MGLUR DESENSITIZATION 275
12.6 METABOTROPIC GLUTAMATE RECEPTORS MODULATE NEURONAL EXCITABILITY 275
12.7 METABOTROPIC GLUTAMATE RECEPTORS MEDIATE AND MODULATE SYNAPTIC TRANSMISSION 277
12.8 PRE- AND POSTSYNAPTIC FUNCTIONAL ASSEMBLY OF METABOTROPIC GLUTAMATE RECEPTORS 278
12.9 PHYSIOLOGICAL ROLES OF METABOTROPIC GLUTAMATE RECEPTOR – A STUDY OF KNOCK-OUT MODELS 279
12.10 SUMMARY 280
FURTHER READING 281
Chapter 13 Somato-dendritic processing of postsynaptic potentials I: Passive properties of dendrites 282
13.1 PROPAGATION OF EXCITATORY AND INHIBITORY POSTSYNAPTIC POTENTIALS THROUGH THE DENDRITIC ARBORIZATION 283
13.2 SUMMATION OF EXCITATORY AND INHIBITORY POSTSYNAPTIC POTENTIALS 285
13.3 SUMMARY 287
FURTHER READING 289
Chapter 14 Subliminal voltage-gated currents of the somato-dendritic membrane 290
14.1 OBSERVATIONS AND QUESTIONS 291
14.2 THE SUBLIMINAL VOLTAGE-GATED CURRENTS THAT DEPOLARIZE THE MEMBRANE 291
14.3 THE SUBLIMINAL VOLTAGE-GATED CURRENTS THAT HYPERPOLARIZE THE MEMBRANE 298
14.4 CONCLUSIONS 303
FURTHER READING 304
Chapter 15 Somato-dendritic processing of postsynaptic potentials II. Role of subliminal depolarizing voltage-gated currents 305
15.1 PERSISTENT Na[sup(+)] CHANNELS ARE PRESENT IN SOMA AND DENDRITES OF NEOCORTICAL NEURONS I[sub(NaP)] BOOSTS EPSPs IN AMPLITUDE AND DURATION306
15.2 T-TYPE Ca[sup(2+)] CHANNELS ARE PRESENT IN DENDRITES OF NEOCORTICAL NEURONS I[sub(CaT)] BOOSTS EPSPs IN AMPLITUDE AND DURATION308
15.3 THE HYPERPOLARIZATION ACTIVATED CATIONIC CURRENT I[sub(H)] IS PRESENT IN DENDRITES OF HIPPOCAMPAL PYRAMIDAL NEURONS FOR EPSPs, DENDRITIC…314
15.4 FUNCTIONAL CONSEQUENCES 316
15.5 CONCLUSIONS 318
FURTHER READING 318
Chapter 16 Somato-dendritic processing of postsynaptic potentials III. Role of high-voltage-activated depolarizing currents 319
16.1 HIGH-VOLTAGE-ACTIVATED Na[sup(+)] AND/OR Ca[sup(2+)] CHANNELS ARE PRESENT IN THE DENDRITIC MEMBRANE OF SOME CNS NEURONS, BUT ARE THEY DISTRIBUTED WITH COMPARABLE… 319
16.2 HIGH-VOLTAGE-ACTIVATED Ca[sup(2+)] CHANNELS ARE PRESENT IN THE DENDRITIC MEMBRANE OF SOME CNS NEURONS, BUT ARE THEY DISTRIBUTED WITH COMPARABLE DENSITIES… 329
16.3 FUNCTIONAL CONSEQUENCES 332
16.4 CONCLUSIONS 334
FURTHER READING 335
Chapter 17 Firing patterns of neurons 336
17.1 MEDIUM SPINY NEURONS OF THE NEOSTRIATUM ARE SILENT NEURONS THAT RESPOND WITH A LONG LATENCY 336
17.2 INFERIOR OLIVARY CELLS ARE SILENT NEURONS THAT CAN OSCILLATE 339
17.3 PURKINJE CELLS ARE PACEMAKER NEURONS THAT RESPOND BY A COMPLEX SPIKE FOLLOWED BY A PERIOD OF SILENCE 343
17.4 THALAMIC AND SUBTHALAMIC NEURONS ARE PACEMAKER NEURONS WITH TWO INTRINSIC FIRING MODES: A TONIC AND A BURSTING MODE 346
FURTHER READING 352
Chapter 18 Synaptic plasticity 353
18.1 SHORT-TERM POTENTIATION (STP) OF A CHOLINERGIC SYNAPTIC RESPONSE AS AN EXAMPLE OF SHORT-TERM PLASTICITY: THE CHOLINERGIC RESPONSE OF MUSCLE CELLS… 353
18.2 LONG-TERM POTENTIATION (LTP) OF A GLUTAMATERGIC SYNAPTIC RESPONSE: EXAMPLE OF THE GLUTAMATERGIC SYNAPTIC RESPONSE OF PYRAMIDAL NEURONS OF THE CA1 REGION OF… 355
18.3 THE LONG-TERM DEPRESSION (LTD) OF A GLUTAMATERGIC RESPONSE: EXAMPLE OF THE RESPONSE OF PURKINJE CELLS OF THE CEREBELLUM TO PARALLEL FIBRE STIMULATION 366
FURTHER READING 375
APPENDIX 18.1 DEPOLARIZATION-INDUCED SUPPRESSION OF INHIBITION (DSI): AN EXAMPLE OF SHORT-TERM PLASTICITY AT GABAERGIC SYNAPSES 376
FURTHER READING 378
Chapter 19 The adult hippocampal network 379
19.1 OBSERVATIONS AND QUESTIONS 379
19.2 THE HIPPOCAMPAL CIRCUITRY 380
19.3 ACTIVATION OF INTERNEURONS EVOKE INHIBITORY GABAERGIC RESPONSES IN POSTSYNAPTIC PYRAMIDAL CELLS 383
19.4 ACTIVATION OF PRINCIPAL CELLS EVOKES EXCITATORY GLUTAMATERGIC RESPONSES IN POSTSYNAPTIC INTERNEURONS AND OTHER PRINCIPAL CELLS (SYNCHRONIZATION IN CA3) 391
19.5 OSCILLATIONS IN THE HIPPOCAMPAL NETWORK: EXAMPLE OF SHARP WAVES (SPW) 393
19.6 SUMMARY 395
FURTHER READING 396
Chapter 20 Maturation of the hippocampal network 397
20.1 GABAERGIC NEURONS AND GABAERGIC SYNAPSES DEVELOP PRIOR TO GLUTAMATERGIC ONES 397
20.2 GABA[sub(A)]- AND GABA[sub(B)]-MEDIATED RESPONSES DIFFER IN DEVELOPING AND MATURE BRAINS 401
20.3 MATURATION OF COHERENT NETWORKS ACTIVITIES 405
20.4 CONCLUSIONS 408
FURTHER READING 409
Index 410
A 410
B 410
C 410
D 411
E 411
F 411
G 412
H 413
I 413
K 413
L 413
M 414
N 414
O 415
P 415
Q 416
R 416
S 416
T 417
U 417
V 417
W 417
X 417
Y 417