Cellular and Molecular Neurobiology (Deluxe Edition) (eBook)

Front Cover 1
Cellular and Molecular Neurobiology 4
Copyright Page 5
Contents 6
Contributors 23
Acknowledgements 25
Part 1: Neurons: Excitable and Secretory Cells that Establish Synapses 26
Chapter 1. Neurons 28
1.1 Neurons have a cell body from which emerge two types of processes: the dendrites and the axon 28
1.2 Neurons are highly polarized cells with a differential distribution of organelles and proteins 32
1.3 Axonal transport allows bidirectional communication between the cell body and the axon terminals 36
1.4 Neurons connected by synapses form networks or circuits 42
1.5 Summary: the neuron is an excitable and secretory cell presenting an extreme functional regionalization 43
Appendix 1.1 The cytoskeletal elements in neurons 46
Further reading 47
Chapter 2. Neuron–Glial Cell Cooperation 49
2.1 Astrocytes form a vast cellular network or syncytium between neurons, blood vessels and the surface of the brain 49
2.2 Oligodendrocytes form the myelin sheaths of axons in the central nervous system and allow the clustering of Na+ channels at nodes of Ranvier 51
2.3 Microglia: ramified microglial cells represent the quiescent form of microglial cells in the central nervous system they transform upon injury
2.4 Ependymal cells constitute an active barrier between blood and cerebrospinal fluid 56
2.5 Schwann cells are the glial cells of the peripheral nervous system they form the myelin sheath of axons or encapsulate neurons
Further reading 58
Chapter 3. Ionic Fluxes Across the Neuronal Plasma Membrane 61
3.1 Observation and questions 61
3.2 Na+, K+, Ca2+ and Cl– ions passively cross the plasma membrane through transmembrane proteins – the channels 64
3.3 The diffusion of ions through an open channel: What is an electrochemical gradient and an ionic current? 72
3.4 Active transport of Na+, K+, Ca2+ and Cl– ions by pumps and transporters maintain the unequal distribution of ions 77
3.5 Summary 78
Appendix 3.1 Hydrophobicity profile of a transmembrane protein 79
Appendix 3.2 The Nernst equation 80
Further reading 81
Chapter 4. Basic Properties of Excitable Cells at Rest 82
4.1 Ionic channels open at rest determine the resting membrane potential 82
4.2 Membrane pumps are responsible for keeping constant the concentration gradients across membranes 86
4.3 A simple equivalent electrical circuit for resting membrane properties 87
4.4 Advantages and disadvantages of sharp (intracellular) versus patch electrodes for measuring the resting membrane potential 90
4.5 Background currents which flow through voltage-gated channels open at resting membrane potential also participate in Vrest 92
Further reading 92
Chapter 5. The Voltage-Gated Channels of Na+ Action Potentials 94
5.1 Properties of action potentials 94
5.2 The depolarization phase of Na+-dependent action potentials results from the transient entry of Na+ ions through voltage-gated Na+ channels 96
5.3 The repolarization phase of the sodium-dependent action potential results from Na+ channel inactivation and partly from K+ channel activation 112
5.4 Sodium-dependent action potentials are initiated at the axon initial segment in response to a membrane depolarization and then actively propagate along the axon 119
Appendix 5.1 Current clamp recording 124
Appendix 5.2 Voltage clamp recording 126
Appendix 5.3 Patch clamp recording 127
Further reading 134
Chapter 6. The Voltage-Gated Channels of Ca2+ Action Potentials: Generalization 136
6.1 Properties of Ca2+-dependent action potentials 136
6.2 The depolarizing or plateau phase of Ca2+-dependent action potentials results from the transient entry of Ca2+ ions through voltage-gated Ca2+ channels 137
6.3 The repolarization phase of Ca2+-dependent action potentials results from the activation of K+ currents IK and IK(Ca) 148
6.4 Calcium-dependent action potentials are initiated in axon terminals or in dendrites 153
6.5 A note on voltage-gated channels and action potentials 156
Appendix 6.1 Fluorescence measurements of intracellular Ca2+ concentration 156
Appendix 6.2 Tail currents 164
Further reading 165
Chapter 7. The Chemical Synapses 167
7.1 The synaptic complex’s three components: presynaptic element, synaptic cleft and postsynaptic element 167
7.2 The interneuronal synapses 174
7.3 The neuromuscular junction is the group of synaptic contacts between the terminal arborization of a motor axon and a striated muscle fibre 177
7.4 The synapse between the vegetative postganglionic neuron and the smooth muscle cell 181
7.5 Example of a neuroglandular synapse 184
7.6 Summary 185
Appendix 7.1 Neurotransmitters, agonists and antagonists 185
Appendix 7.2 Identification and localization of neurotransmitters and their receptors 187
Further reading 192
Chapter 8. Neurotransmitter Release 194
8.1 Observations and questions 194
8.2 Presynaptic processes I: From presynaptic spike to [Ca2+]i increase 199
8.3 Presynaptic processes II: From [Ca2+]i increase to synaptic vesicle fusion 205
8.4 Processes in the synaptic cleft: from transmitter release in the cleft to transmitter clearance from the cleft 213
8.5 Summary 216
Appendix 8.1 Quantal nature of neurotransmitter release 218
Appendix 8.2 The probabilistic nature of neurotransmitter release 219
Further reading 223
Part 2: Ionotropic and Metabotropic Receptors in Synaptic Transmission and Sensory Transduction 224
Chapter 9. The Ionotropic Nicotinic Acetylcholine Receptors 226
9.1 Observations 227
9.2 The torpedo or muscle nicotinic receptor of acetylcholine is a heterologous pentamer a2ß.d 227
9.3 Binding of two acetylcholine molecules favours conformational change of the protein towards the open state of the cationic channel 233
9.4 The nicotinic receptor desensitizes 239
9.5 nAChR-mediated synaptic transmission at the neuromuscular junction 242
9.6 Nicotinic transmission pharmacology 246
9.7 Summary 248
Appendix 9.1 The neuronal nicotinic receptors 249
Further reading 250
Chapter 10. The Ionotropic GABAA Receptor 252
10.1 Observations and questions 252
10.2 GABAA receptors are hetero-oligomeric proteins with a structural heterogeneity 252
10.3 Binding of two GABA molecules leads to a conformational change of the GABAA receptor into an open state the GABAA receptor desensitizes
10.4 Pharmacology of the GABAA receptor 262
10.5 GABAA-mediated synaptic transmission 268
10.6 Summary 274
Appendix 10.1 Mean open time and mean burst duration of the GABAA single-channel current 274
Further reading 275
Chapter 11. The Ionotropic Glutamate Receptors 276
11.1 The three different types of ionotropic glutamate receptors have a common structure and participate in fast glutamatergic synaptic transmission 276
11.2 AMPA receptors are an ensemble of cationic receptor-channels with different permeabilities to Ca2+ ions 278
11.3 Kainate receptors are an ensemble of cationic receptor channels with different permeabilities to Ca2+ ions 282
11.4 NMDA receptors are cationic receptor-channels highly permeable to Ca2+ ions they are blocked by Mg2+ ions at voltages close to the resting potential, which confers strong voltage dependence
11.5 Synaptic responses to glutamate are mediated by NMDA and non-NMDA receptors 292
11.6 Summary 297
Further reading 297
Chapter 12. Ionotropic Mechanoreceptors: the Mechanosensitive Channels 299
12.1 Mechanoreception in sensory neurons is associated with the production of a receptor potential 299
12.2 Discovery of mechanosensitive ion channels provided a potential molecular mechanism for mechanotransduction 299
12.3 Structural basis for the mechanical gating of ion channels 300
12.4 Classification of stretch-sensitive ion channels 301
12.5 Mechanosensitive ion channels and mechanotransduction 303
12.6 Osmoreceptors in the central nervous system 303
12.7 Osmoreception in magnocellular neurosecretory cells 306
12.8 Conclusions 309
Further reading 311
Chapter 13. The Metabotropic GABAB Receptors 312
13.1 GABAB receptors were originally discovered because of their insensitivity to bicuculline and their sensitivity to baclofen 312
13.2 Structure of the GABAB receptor 313
13.3 GABAB receptors are G-protein-coupled to a variety of different effector mechanisms 317
13.4 The functional role of GABAB receptors in synaptic activity 333
13.5 Summary 337
Further reading 338
Chapter 14. The Metabotropic Glutamate Receptors 339
14.1 What is the receptor underlying glutamate-stimulated PI hydrolysis? – The cloning of metabotropic glutamate receptor genes 339
14.2 How do metabotropic glutamate receptors carry out their function? – Structure–function studies of metabotropic glutamate receptors 340
14.3 What biochemical means do metabotropic glutamate receptors utilize to elicit physiological changes in the nervous system? – Signal transduction studies of metabotropic glutamate receptors 342
14.4 What are the functions of metabotropic glutamate receptors in the nervous system? – Physiological and genetic studies of mGluRs 344
14.5 How are metabotropic glutamate receptors specifically localized in neurons to execute their functions? – Studies of mGluR postsynaptic localization 348
14.6 How is the activity of metabotropic glutamate receptors modulated? – Studies of mGluR desensitization 349
14.7 Summary 350
Further reading 350
Chapter 15. The Metabotropic Olfactory Receptors 352
15.1 The olfactory receptor cells are sensory neurons located in the olfactory neuroepithelium 352
15.2 The response of olfactory receptor neurons to odours is a membrane depolarization which elicits action potential generation 354
15.3 Odorants bind to a family of G-protein-linked receptors which activate adenylate cyclase 355
15.4 cAMP opens a cyclic nucleotide-gated channel and generates an inward current 357
15.5 The odorant-evoked inward current evokes a membrane depolarization that spreads electronically to the axon hillock where it can elicit action potentials 368
15.6 Conclusions 370
Further reading 370
Part 3: Somato-Dendritic Processing and Plasticity of Postsynaptic Potentials 372
Chapter 16. Somato-Dendritic Processing of Postsynaptic Potentials. I: Passive Properties of Dendrites 374
16.1 Propagation of excitatory and inhibitory postsynaptic potentials through the dendritic arborization 375
16.2 Summation of excitatory and inhibitory postsynaptic potentials 376
16.3 Summary 379
Further reading 380
Chapter 17. Subliminal Voltage-Gated Currents of the Somato-Dendritic Membrane 383
17.1 Observations and questions 383
17.2 The subliminal voltage-gated currents that depolarize the membrane 384
17.3 The subliminal voltage-gated currents that hyperpolarize the membrane 392
17.4 Conclusions 397
Further reading 397
Chapter 18. Somato-Dendritic Processing of Postsynaptic Potentials. II. Role of Subliminal Depolarizing Voltage-Gated Currents 399
18.1 Persistent Na+ channels are present in soma and dendrites of neocortical neurons INaP boosts EPSPs in amplitude and duration
18.2 T-type Ca2+ channels are present in dendrites of neocortical neurons ICaT boosts EPSPs in amplitude and duration
18.3 The hyperpolarization-activated cationic current Ih is present in dendrites of hippocampa pyramidal neurons for EPSPs, dendritic Ih decreases the current transmitted from the dendrites to the soma
18.4 Functional consequences 411
18.5 Conclusions 411
Further reading 412
Chapter 19. Somato-Dendritic Processing of Postsynaptic Potentials. III. Role of High-Voltage-Activated Depolarizing Currents 413
19.1 High-voltage-activated Na+ and/or Ca2+ channels are present in the dendritic membrane of some CNS neurons, but are they distributed with comparable densities in soma and dendrites? 415
19.2 High-voltage-activated Ca2+ channels are present in the dendritic membrane of some CNS neurons, but are they distributed with comparable densities in soma and dendrites? 423
19.3 Functional consequences 428
19.4 Conclusions 430
Further reading 431
Chapter 20. Firing Patterns of Neurons 432
20.1 Medium spiny neurons of the neostriatum are silent neurons that respond with a long latency 432
20.2 Inferior olivary cells are silent neurons that can oscillate 435
20.3 Purkinje cells are pacemaker neurons that respond by a complex spike followed by a period of silence 439
20.4 Thalamic and subthalamic neurons are pacemaker neurons with two intrinsic firing modes: a tonic and a bursting mode 442
Further reading 448
Chapter 21. Synaptic Plasticity 449
21.1 Short-term potentiation (STP) of a cholinergic synaptic response as an example of short-term plasticity: the cholinergic response of muscle cells to motoneuron stimulation 449
21.2 Long-term potentiation (LTP) of a glutamatergic synaptic response: example of the glutamatergic synaptic response of pyramidal neurons of the CA1 region of the hippocampus to Schaffer collaterals activation 450
21.3 The long-term depression (LTD) of a glutamatergic response: example of the response of Purkinje cells of the cerebellum to parallel fibre stimulation 462
Further reading 473
Part 4: Activity and Development of Networks: The Hippocampus as an Example 474
Chapter 22. The Adult Hippocampal Network 476
22.1 Observations and questions 476
22.2 The hippocampal circuitry 478
22.3 Activation of interneurons evoke inhibitory GABAergic responses in postsynaptic pyramidal cells 481
22.4 Activation of principal cells evokes excitatory glutamatergic responses in postsynaptic interneurons and other principal cells (synchronization in CA3) 487
22.5 Oscillations in the hippocampal network: example of sharp waves (SPW) 491
22.6 Summary 492
Further reading 495
Chapter 23. Maturation of the Hippocampal Network 497
23.1 GABAergic neurons and GABAergic synapses develop prior to glutamatergic ones 497
23.2 GABAA- and GABAB-mediated responses differ in developing and mature brains 501
23.3 Network-driven giant depolarizing potentials (GDPs) provide most of the synaptic activity in the neonatal hippocampus 505
23.4 Hypotheses on the role of the sequential expression of GABA- and glutamate-mediated currents and of giant depolarizing potentials 508
23.5 Conclusions 508
Further reading 509
Index 510