GABA and the Basal Ganglia (eBook)

E. D. Abercrombie, J. P. Bolam, J. M. Tepper (Herausgeber)

eBook Download: PDF

2007 | 1. Auflage
350 Seiten
Elsevier Science (Verlag)
978-0-08-048047-3 (ISBN)

Infos

Over the past 25 years the amount of data pertaining to the GABAergic function in the basal ganglia has increased dramatically. GABA and the Basal Ganglia - From Molecules to Systems is a comprehensive review of the current state-of-the-art of knowledge about the neuroanatomy, neuropharmacology and neurophysiology of the basal ganglia, focusing on its GABAergic microcircuitry. It serves as a complete reference to the body of knowledge about the basal ganglia, its constituent neurons, and their interconnections. This volume is designed to serve as a convenient all-in-one review and reference for experienced basal ganglia researchers as well as an introduction to the functional organization of the basal ganglia and its GABAergic circuitry for students and researchers new to the field.

* Reviews the anatomy, physiology and pharmacology of the basal ganglia itself in addition to focusing on the GABAergic circuitry of the basal ganglia
* Authors of each chapter leading internationally acclaimed experts in basal ganglia research

Inhalt

Cover 1
Copyright page 5
List of Contributors 6
Preface 8
Contents 10
Section I: Fundamentals of GABA in the Basal Ganglia 12
Chapter 1. Basal ganglia macrocircuits 14
Acknowledgements 17
References 17
Chapter 2. GABA: Homeostatic and pharmacological aspects 20
GABA metabolism 20
GABA release and uptake 23
Pharmacology of metabolism and uptake 25
Concluding remarks 27
Acknowledgements 27
References 27
Chapter 3. GABAA receptors: structure and function in the basal ganglia 32
GABAA receptors: genes 33
GABAA receptor structure 34
GABAA receptor gating by agonist 36
Subunit assembly rules for GABAA receptors 37
Synaptic GABAA receptors: aß. subunit combinations and anchoring role of the .2 subunit and gephyrin 37
GABAA receptor occupancy at synapses is dynamic 38
Extrasynaptic GABAA receptors: a4ßd subtype 38
GABAA receptors: how subunit combinations affect synaptic and extrasynaptic transmission 39
GABAA receptor agonists, antagonists and allosteric modulators 40
Regulation of GABAA receptor function by neuromodulators: the role of kinases and phosphatases 43
Function and physiological significance of GABAA receptor diversity for the basal ganglia 44
Expression of GABAA receptor subunit genes in the basal ganglia 44
Acknowledgements 47
References 47
Chapter 4. GABAB receptors: structure and function 54
Introduction 54
Molecular characterization/structure 56
Pharmacology 62
References 65
Chapter 5. The cellular, molecular and ionic basis of GABAA receptor signalling 70
Introduction 70
Molecular basis of GABAA receptor function 71
Ionic permeability of GABAA receptors 73
GABAA receptor channel conductance 73
GABA concentration changes at the synapse 74
GABAA receptor gating and the IPSC 75
Tonic activity of GABAA receptors 77
Neuronal ion regulation and the driving force for GABAA receptor-mediated currents 79
Neuronal chloride regulation 81
Neuronal pH regulation and EGABA 83
The ‘‘developmental switch’’ from depolarization to hyperpolarization 84
Ionic plasticity of GABAA receptor-mediated signalling 85
Ionic mechanisms of GABAergic inhibition in substantia nigra 86
Conclusion 87
References 88
Section II: GABAergic Microcircuits of the Basal Ganglia 100
Chapter 6. GABAergic inhibition in the neostriatum 102
Most striatal neurons are GABAergic, but most striatal synapses are not 102
Spatial distribution of GABAergic synapses on spiny cells 104
How can inhibition be effective when so outnumbered? 105
Feedforward and feedback inhibition 107
Winner-take-all inhibition in the striatum? 108
Could groups of spiny cells compete with each other? 109
Inhibition and the mechanism of up and down states in vivo 111
Why is Sp . Sp inhibition so weak? 113
The reversal potential of GABAA 115
Dendritic inhibition probably acts in the dendrites 118
References 118
Chapter 7. Globus pallidus external segment 122
Anatomical organization of the GPe 122
Physiologically distinct types of GPe neurons 123
Afferent projections of the GPe 123
Efferent projections of the GPe 125
Postsynaptic GABAergic responses 126
Presynaptic modulation 135
Metabotropic glutamate receptors 137
Postsynaptic modulations 138
Possible modulations by ambient GABA 138
GPe activity in patients and animal models of Parkinson’s disease 138
Conclusions 139
Acknowledgments 139
References 139
Chapter 8. Globus pallidus internal segment 146
Introduction 146
Cellular types of GPi neurons 147
Basic circuitry of the GPi 147
Origin of GABA in the GPi 148
Localization of GABA receptors and transporters in the GPi 149
GPi activity controlled by GABA 151
GPi activity during movements 153
GABA in the GPi and movement disorders 155
Conclusions 157
Abbreviations 157
Acknowledgments 157
References 158
Chapter 9. The pars reticulata of the substantia nigra: a window to basal ganglia output 162
Neuronal types 163
Cytoarchitecture and functional compartmentalization 164
Functional properties of SNr cells 168
The striatonigral input 170
The pallidonigral input 171
The subthalamonigral input 172
Local interactions between SNr cells 174
Regulation by neuromodulators 174
Conclusion and perspectives 175
References 175
Chapter 10. GABAergic control of the subthalamic nucleus 184
Introduction 184
Afferents of the STN 185
Electrophysiological properties of STN neurons 186
Principles of inhibitory synaptic integration in the STN 187
Enhancement of excitatory synaptic integration by GABAergic inhibition in the STN 191
Regulation of GABAergic inhibition in the STN by dopamine 193
Patterning of STN activity in vivo: proven and potential roles for GABAergic inhibition 195
Acknowledgements 197
References 197
Chapter 11. GABAergic control of substantia nigra dopaminergic neurons 200
Introduction 201
GABAergic synaptic responses in dopaminergic neurons 204
GABAergic inputs from the pars reticulata 209
Differences in GABAA responses between dopaminergic and GABAergic neurons 212
Conclusions 214
Acknowledgments 215
References 215
Chapter 12. GABAergic output of the basal ganglia 220
Outputs of the basal ganglia 220
An example of basal ganglia-controlled functions „ Saccadic eye movement 221
Functions of basal ganglia GABAergic outputs 224
Basal ganglia GABAergic control of basic movements 226
References 230
Section III: GABAergic Neurotransmission in the Basal Ganglia 238
Chapter 13. Localization of GABA receptors in the basal ganglia 240
Technical issues 241
Localization of GABA receptors in the striatum 243
Localization GABA receptors in the globus pallidus (internal and external) 246
Localization GABA receptors in the substantia nigra 246
Localization GABA receptors in the subthalamic nucleus 251
Summary and conclusions 251
Acknowledgments 252
References 252
Chapter 14. Presynaptic modulation of GABA release in the basal ganglia 256
Introduction 256
Autoreceptors 257
Heteroreceptors 261
Retrograde signaling 263
Concluding remarks 266
Abbreviations 266
Acknowledgments 266
References 266
Chapter 15. Development of striatal fast-spiking GABAergic interneurons 272
Introduction 272
Electrophysiological properties of striatal fast-spiking GABAergic interneurons during postnatal development 273
Neurochemical control of striatal fast-spiking GABAergic interneuron development 279
Conclusions 281
Abbreviations 282
Acknowledgments 282
References 282
Chapter 16. Co-localization of GABA with other neuroactive substances in the basal ganglia 284
Location of neuropeptides and receptors in MSNs 284
Dopamine agonists increase neuropeptide expression in MSNs 286
Neuropeptide regulation of local striatal circuitry 287
Conclusion 291
Acknowledgment 292
References 292
Section IV: Systems Level Aspects of GABA in the Basal Ganglia 296
Chapter 17. GABAergic circuits in the basal ganglia and movement disorders 298
Anatomy and function of GABAergic circuits in the basal ganglia 298
Hypokinetic disorders 300
Hyperkinetic disorders 307
Conclusion 313
Abbreviations 313
References 314
Chapter 18. Simulation of GABA function in the basal ganglia: computational models of GABAergic mechanisms in basal ganglia function 324
Introduction 324
Insights into inhibitory circuits from artificial neural networks 326
Challenges to the concept of lateral inhibition 328
Anatomy of spiny projection neuron interconnections in the striatum 329
Synaptic organisation of the neural network of the striatum: spiny–spiny connections 330
Towards a realistic computational model of the spiny cell network 333
Results of the computer simulation 334
Other GABAergic computations in the striatum 336
Discussion 337
Acknowledgments 337
References 337
Subject Index 342

Produkt-Details

• Erscheint lt. Verlag: 17.4.2007
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Humanbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Zoologie
• Themenwelt: Technik
• ISBN-10: 0-08-048047-0 / 0080480470
• ISBN-13: 978-0-08-048047-3 / 9780080480473