History of the Synapse

Book Cover......Page 1
Half-Title......Page 2
Dedication......Page 3
Title......Page 4
Copyright......Page 5
Contents......Page 6
Introduction......Page 10
1.1 Plato and Aristotle: ‘vital pneuma’ is necessary to initiate organ function......Page 13
1.2 Galen: pneuma is conducted and transmitted from nerve to muscle......Page 15
1.3 Descartes: the replacement of pneuma by mechanical corpuscles......Page 16
1.4 Borelli: a corpuscular description of conduction and transmission......Page 18
1.5 Fontana: nerves are composed of many cylinders along each of which conduction occurs......Page 20
1.6 Galvani: electricity is conducted and transmitted not corpuscles......Page 21
1.7 Matteucci and du Bois-Reymond: transient electrical changes are conducted (the action potential)......Page 24
1.8 Helmholtz: the action potential has a finite velocity......Page 27
1.9 Kuhne and Auerbach: identifying the structure of nerve endings on muscle and neurons......Page 28
1.10 Cajal: nerve endings are not continuous with the cells on which they impinge......Page 30
1.11 Sherrington: the adoption of the word ‘synapse’......Page 34
2.1 Research on the Synapse in the Laboratories of Sherrington and Langley before the Great War......Page 38
2.2 Sherrington’s concept of the inhibitory and excitatory states of central synapses......Page 40
2.3 Lucas, Adrian and the electrical concept of the inhibitory state of central synapses......Page 41
2.5 Eccles develops the electrical concept of the excitatory state at autonomic synapses......Page 44
2.6 Katz, Kuffler and Eccles establish the motor endplate as the paradigm synapse for electrophysiology......Page 47
2.7 Eccles elucidates the electrical signs of the inhibitory and excitatory states of central synapses......Page 48
2.8 Katz’s concept of quantal transmitter release at the motor endplate and the vesicle hypothesis......Page 51
2.9 Conclusion: the establishment of Sherrington’s concept of the synapse in the central nervous system and central synaptic transmission......Page 53
3.1 Introduction......Page 55
3.2 Claude Bernard and curarization: the notion of an intermediate zone between nerve and muscle......Page 56
3.4 John Langley and T.R.Elliott: the emergence of the concept of chemical transmission between sympathetic nerves and smooth muscle......Page 58
3.5 The action of curare and John Langley’s development of the idea of transmitter receptors......Page 63
3.7 The discovery of acetylcholine and its physiological action at autonomic neuroeffector junctions......Page 66
3.8 The physiological action of acetylcholine in autonomic ganglia......Page 71
3.9 The identity of acetylcholine as the transmitter substance at somatic neuromuscular junctions......Page 72
3.10 The discovery of the physiological action of single acetylcholine receptors......Page 73
3.11 Conclusion......Page 76
4.2 Early observations leading to the idea of autoreceptors......Page 77
4.3 Direct experimental evidence for autoreceptors......Page 80
4.4 Identification of presynaptic adrenergic autoreceptors different from postsynaptic adrenergic receptors......Page 83
4.6 Evidence that endogenous autoreceptor mechanisms exist......Page 84
4.7 The ionic basis of the action of alpha 2 adrenoceptors......Page 85
4.8 Conclusion......Page 88
5.2 Identification of excitant and depressant amino acids......Page 89
5.3 Glycine accepted as an inhibitory transmitter in the spinal cord......Page 90
5.4 The emergence of GABA as an inhibitory transmitter in the brain......Page 93
5.5 L-Glutamate as a neurotransmitter: synaptic excitation, ion fluxes and neurotransmitter transporters......Page 96
5.6 NMDA receptors: the first amino acid receptor identified at central excitatory synapses......Page 98
5.9 Conclusion......Page 99
6.2 Chlorpromazine......Page 102
6.4 The dopamine hypothesis for neuroleptics......Page 103
6.6 Identification of the D1-like and D2-like dopamine receptors......Page 104
6.8 Clozapine......Page 107
6.9 Distribution of D1 and D2 receptors in the striatum of schizophrenics......Page 110
6.11 Cellular and molecular mechanisms of action of dopamine receptors......Page 114
6.12 The time course of action of neuroleptics on dopamine receptors and the emergence of antipsychotic effects......Page 115
6.13 Conclusion......Page 116
7.1 Introduction: J.N.Langley, H.H.Dale and non-adrenergic non-cholinergic (NANC) transmission......Page 117
7.1.1 J.N.Langley: defining the autonomic nervous system......Page 119
7.1.2. H.H.Dale: emergence of the classical autonomic paradigm......Page 120
7.2.1 Parasympathetic excitatory nerves in the gastrointestinal tract resistant to atropine......Page 121
7.2.2 Parasympathetic inhibitory nerves exist in the gastrointestinal tract......Page 124
7.2.3 Parasympathetic inhibitory nerves in the gastrointestinal tract and the release of adrenaline......Page 126
7.2.4 Doubts arise concerning the possibility that parasympathetic inhibitory nerve terminals release adrenaline......Page 127
7.3.1 Discovery of the electrical signs of inhibitory transmission: the inhibitory junction potential......Page 128
7.3.2 Rebound excitation following inhibitory transmission: atropine-resistant excitatory junctions......Page 131
7.3.3 Discovery that inhibitory junctional transmission involves non-adrenergic non-cholinergic (NANC) transmitters......Page 132
7.4 NANC transmission: the new autonomic paradigm......Page 133
7.5.1 Identification of a fast and a slow IJP......Page 139
7.5.2 Contributions of nitric oxide to the IJPs......Page 141
7.5.3 Contributions of vasoactive intestinal peptide (VIP) to IJP......Page 142
7.5.5 Contribution of carbon monoxide to the IJP......Page 143
7.6.1 Modulation of potassium channels by NANC transmitters......Page 144
7.7.2 Storage and secretion of NANC transmitters from inhibitory motoneurones......Page 145
7.8.2 Rebound excitation; identity of NANC excitatory transmitters......Page 146
7.9 Conclusion......Page 147
8.2 Calcium is necessary for the release of transmitter......Page 148
8.3 Electrophysiological evidence that calcium is necessary for the release of transmitter: the concept of a calcium sensor for secretion......Page 149
8.4.1 Induced calcium action potentials in invertebrate muscles......Page 152
8.4.3 Naturally occuring sodium-calcium action potentials in invertebrate neurons......Page 154
8.5 Are calcium movements across the nerve terminal necessary for evoked secretion?......Page 155
8.6 Direct evidence for calcium entry across the nerve terminal membrane during an impulse......Page 159
8.7.1 Calcium currents and evidence for calcium channels......Page 161
8.7.3 Identification of different calcium channel types......Page 163
8.7.4 Identification of the different calcium channel types involved in transmitter release......Page 165
8.7.5 Calcium channels and the transfer function of the nerve terminal......Page 167
8.8.2 Physiological evidence that synaptotagmin is the calcium-sensor molecule......Page 170
8.9 Conclusion......Page 174
9.1.2. Statistical methods introduced to describe quantal release......Page 176
9.2.1.1 Binomial theory......Page 177
9.2.2.1 Theory......Page 178
9.2.2.2 Experiments on amphibian neuromuscular junctions......Page 179
9.2.3.1 Experiments on crayfish and crab neuromuscular junctions......Page 180
9.2.4.1 Zucker’s determination of parameters......Page 181
9.2.5.1 Theory......Page 182
9.2.5.2 Experiments on newly formed amphibian neuromuscular junctions......Page 183
9.2.6.1 Theory......Page 184
9.3 Kinetics of release of a quantum......Page 189
9.3.2 A kinetic model of quantal secretion at synapses with uniform p......Page 190
9.3.2.1 Theory......Page 191
9.3.3.1 Theory......Page 193
9.3.3.2 Experimental results on the amphibian neuromuscular junction......Page 197
9.4.1 Multimodal distributions......Page 198
9.4.2 Binomial distributions and deconvolution......Page 199
9.5.1 AC Scoring......Page 202
9.6 Model discrimination: Statistical methods for discrimination between different statistical models of transmitter release......Page 205
9.6.3 Estimation of the distribution by the log likelihood ratio......Page 206
A.3.1 The normal distribution......Page 207
A. 6.1 Two important statistics......Page 209
A.6.3 Standard errors of functions of random variables......Page 210
A.7.1 The moments of the binomial distribution......Page 211
A.7.2 Derivation of Poisson from the binomial......Page 212
A.7.3. Determination of standard errors for estimates in the binomial case......Page 213
A.8.1 The moments of the compound binomial with a normal variate......Page 215
A.8.2. Derivation of gamma from Poisson......Page 217
A.8.4 Estimating the standard errors of......Page 218
A.9.1 Solving the differential equation......Page 220
A.10.1 Solving the differential equation......Page 221
A.10.2 Determining the average number of releases......Page 223
A.11.1 Secretion from a single site......Page 224
A.11.2 Estimation of parameters......Page 225
A.12.2 The likelihood function......Page 226
A.14 Model comparison using the Wilks test......Page 227
10.1 Introduction: the hippocampus, memory and long-term potentiation (LTP)......Page 228
10.2.2 LTP and senescence......Page 231
10.3 The induction of associative LTP in the brain......Page 232
10.3.1 Associative LTP is blocked by N-methyl-D-aspartate (NMDA) antagonists......Page 233
10.3.3 Magnesium gates NMDA receptor channels: the missing link in the induction of associative LTD......Page 235
10.4.1 Increase in protein synthesis accompanies LTP......Page 238
10.4.2 Increase in the size of dendritic spines......Page 239
10.4.4 Increase in the density of glutamate receptors......Page 240
10.6 Evidence that associative LTP is involved in memory......Page 242
10.8 Summary and Conclusion......Page 245
11.2.1 Site of synapse formation in reinnervated adult muscle......Page 250
11.2.2 Site of synapse formation in developing muscle......Page 254
11.3.1 Elimination of polyneuronal innervation during development of muscles......Page 255
11.3.2 Elimination of polyneuronal innervation during reinnervation of mature muscles......Page 257
11.3.3 A dual-constraint theory for the role of synapse-formation molecules in the elimination of polyneuronal innervation......Page 258
11.4 Elimination of polyneuronal innervation during development described by dual-constraint theory......Page 259
11.4.1 Loss of polyneuronal innervation......Page 260
11.4.2 Emergence of mature motor units......Page 263
11.4.3 Intrinsic withdrawal of motor-synaptic terminals......Page 265
11.5.1 Loss of polyneuronal innervation......Page 267
11.5.2 Reestablishment of mature motor-unit sizes......Page 271
11.6.1 Muscle cell type specification as a mechanism for map formation......Page 274
11.6.2 The influence of impulse traffic on map formation......Page 280
11.7.1 Identification of Agrin as the synaptic terminal (T) synapse formation molecule......Page 283
11.7.3 Identification of MASC as the receptor molecule in the muscle synapse formation molecule complex (R)......Page 287
11.7.5 Identification of S-laminin as a retrograde signal for terminal differentiation......Page 288
11.7.6 The formation of active zones in the nerve terminal......Page 289
11.7.7 Acetylcholine receptor redistribution during loss of polyneuronal innervation......Page 290
11.9.1 Elimination of polyneuronal innervation during development of ganglia......Page 291
11.10.2 After partial denervation......Page 292
11.11.3 Identification of neuregulins like ARIA in autonomic ganglia......Page 293
11.12 Conclusion......Page 294
Epilogue......Page 298
References......Page 300
Illustration Acknowledgements......Page 340
Acknowledgements......Page 344
Index......Page 346