Cortico-Subcortical Dynamics in Parkinson’s Disease (eBook)

Cortico-Subcortical Dynamics in Parkinson’s Disease 2
Contemporary Neuroscience 3
Contents 6
Contributors 9
Part 1: Cortico-Subcortical Circuits and Parkinson’s Disease 14
Leading Toward a Unified Cortico-basal Ganglia Functional Model 15
Basal Ganglia Circuitry: The Direct and Indirect Pathways 15
Functional Changes in the Basal Ganglia After Dopamine Depletion 16
Glutamate Decarboxylase 17
Cytochrome Oxidase 17
2-Deoxyglucose 18
Chronic Dopamine Depletion and Basal Ganglia Oscillations 18
Chronic Dopamine Depletion and Firing Pattern Shift in the Basal Ganglia 19
Corticostriatal Function and Basal Ganglia Oscillations 21
Dopamine-Dependent Regulation of Cortically Driven Oscillatory Activity in the Basal Ganglia and Akinesia 23
Integration of the Motor-Limbic Circuits in the Basal Ganglia 25
Summary and Conclusions 27
References 27
Modeling Parkinson’s Disease: 50 Years Later 35
A Turning Point in the History of Neuroscience: The Discovery of l -Dopa Decarboxylase 35
Modeling Parkinson’s Disease: From DA Depletion to Genetic Manipulations 36
Unilateral DA Depletion Induced by Injecting 6-OHDA into the Brain 37
Modeling PD Pathophysiology with MPTP Intoxication in Mice 38
Environmental Toxins Induce Parkinsonism in Rodents 40
Genetic Models of PD 40
Summary and Conclusions 41
References 42
Part 2: Physiological Studies of the Cortico-subcortical Dynamics and Parkinson’s Disease 47
Phasic Dopaminergic Signaling: Implications for Parkinson’s Disease 48
Phasic Dopamine Activation 49
Purported Functions of Phasic Dopaminergic Signaling 49
Nucleus Accumbens and Associative Learning 52
Dorsolateral Striatum and Stimulus-Response Associations 53
Prefrontal Cortex and Working Memory 54
Dopaminergic Signaling and PD 55
Parkinson’s Disease, Motor and Cognitive Impairments, and Phasic Dopaminergic Signaling 56
Conclusion 59
References 60
Striatal Dendritic Adaptations in Parkinson’s Disease Models 66
Introduction 66
MSN Dendrites are Excitable 67
DA Suppresses While ACh Enhances Dendritic Excitability in the D2 MSNs 69
Disconnection of the Indirect Pathway in PD Models 73
Functional Implications for the Pathophysiology in PD 76
References 77
Diversity of Up-State Voltage Transitions During Different Network States 83
Introduction 83
Striatal Circuit Arrangement 84
The Bistable-Like Behavior of Striatal Medium Spiny Neurons 85
Up and Down Voltage Transitions in MSNs 86
Up-States: Windows for Ensemble Synchronization 90
Conclusions 90
References 92
The Corticostriatal Pathway in Parkinson’s Disease 96
Introduction 96
Corticostriatal Anatomy and Function 96
Dopaminergic Projections and Receptors in the Motor Striatum 97
Striatal Organization 98
Electrophysiological Properties of Striatal D1 and D2 Receptor-Containing MSSNs 99
Mouse Models for Parkinsonism 100
Effects of Dopamine Deficiency on Postsynaptic Corticostriatal Activity 101
Effects of Dopamine Deficiency on Presynaptic Corticostriatal Activity 102
Endocannabinoid-Mediated Modulation of the Corticostriatal Pathway 104
Acetylcholine-Mediated Modulation of Corticostriatal Afferents 105
Summary 106
References 107
Cholinergic Interneuron and Parkinsonism 114
Introduction 114
Cholinergic Interneurons: From Morphological Clues to Functional Evidence 115
Animal Models of Parkinson’s Disease 116
MPTP Model 117
Rotenone Model 117
6-Hydroxydopamine Model 118
Cholinergic Interneurons and Parkinsonism 118
Role of Cholinergic Interneurons in Other Basal Ganglia Disorders 119
Future Perspectives 120
References 122
Basal Ganglia Network Synchronization in Animal Models of Parkinson’s Disease 125
Introduction 125
Dopamine Effects on Rate in Basal Ganglia Circuits 126
Testing Predictions of the Rate-Based Model: Effects of Dopamine Agonists 127
Testing Predictions of the Rate-Based Model: Effects of Dopamine Loss 128
Dopamine Effects on Firing Pattern in Basal Ganglia Circuits 129
Multisecond Oscillations 129
Dopamine Agonist Effects on Incidence and Frequency of Multisecond Oscillations 130
Dopamine Agonist Effects on Synchronization of Multisecond Oscillations in GPe, STN and SNpr 131
1 Hz Oscillations 132
Dopamine Cell Lesion Effects on 1 Hz Oscillations in the Basal Ganglia 133
Dopamine Cell Lesion Effects on Phase Relationships of 1 Hz Oscillations in Basal Ganglia Circuits 135
4-30 Hz Oscillations 138
Dopamine Cell Lesion Effects on 4-30 Hz Oscillations 138
Conclusion 140
References 141
Converging into a Unified Model of Parkinson’s Disease Pathophysiology 151
Slow Waves Versus Activation or Silent Versus Depolarized Network States? 152
Spontaneous Activity Downstream the Striatum 155
Electrical Stimulation as a Tool to Study the Dynamic Activation of Trans-striatal and Trans-subthalamic Pathways 157
Evoked Activity Downstream the Striatum 158
Conclusions 160
References 162
The Corticostriatal Transmission in Parkinsonian Animals: In Vivo Studies 165
Introduction 165
Cortical Inputs to Striatonigral and Striatopallidal Neurons in Intact Animals 165
The Direct and Indirect Striatal Output Pathways 165
Segregation of D1 and D2 Receptors in Striatonigral and Striatopallidal Neurons: Recent Evidence 166
Cortical Inputs to Striatonigral and Striatopallidal Neurons 167
Spontaneous MSN Discharge Activities Generated by Cortical Inputs 168
MSNs Activities Evoked by Cortical Stimulation 169
Feedforward Inhibition of MSNs by FS Interneurons 169
Effects of the Dopaminergic Depletion on the Corticostriatal Transmission 172
Effects of DA Depletion on Striatonigral and Striatopallidal Neurons 172
Effects of DA Depletion on Feedforward Inhibition 172
Origin of the Striatal Dysfunctions 173
Conclusion and Future Prospects 173
References 174
Striatal Nitric Oxide-cGMP Signaling in an Animal Model of Parkinson’s Disease 178
Parkinson’s Disease 178
Striatal Circuitry 179
Role of NO-GC Signaling in Motor Behavior 180
Impact of Partial Striatal DA Depletions on Motor Behavior 180
Impact of DA Depletion on NO-GC Signaling 182
Impact of DA Depletion on Striatal MSN Activity and Striatal Output 184
Conclusions 188
References 188
Dopamine-Endocannabinoid Interactions in Parkinson’s Disease 192
Introduction 192
Overview of the Endogenous Cannabinoid Signaling System 192
Cannabinoid Receptor Distribution in the Brain 193
Endogenous Cannabinoids 194
Endogenous Cannabinoids: Mode of Action in the CNS 195
Dopamine, Cannabinoids and Movement 196
The Role of the Basal Ganglia in Movement 196
Dopamine D1 Receptor-Mediated Changes in Motor Activity 198
Dopamine D2 Receptor-Mediated Changes in Motor Activity 198
Cannabinoid Receptor Activation and Movement 199
Convergence of Dopamine and Cannabinoid Receptor Activation: Implications for Motor Control 200
Dopamine and Endogenous Cannabinoid Interactions in Striatum 201
Cannabinoids Exert Excitatory Control over Dopamine Neurotransmission 201
Endogenous Cannabinoid and Dopamine Dynamics in the Hypodopaminergic State 202
Potential for Therapeutic Use of Cannabinoid Receptor Modulators for Parkinson’s Disease 203
Role of Endogenous Cannabinoid Signaling in Parkinson’s Disease 203
Therapeutic Use of CB1 Receptor Antagonists 204
Therapeutic Use of CB1 Receptor Agonists 205
Concluding Remarks 205
References 206
Glutamate Plasticity in an Animal Model of Parkinson’s Disease 213
Time-Dependent Changes in Striatal Glutamate Following Loss of Dopamine 214
Electron Microscopy/Immunocytochemistry 214
In Vivo Microdialysis 218
Glutamate Plasticity in the Substantia Nigra Pars Reticulata 221
Alterations in Glutamate in the Subthalamic Nucleus 223
Overall Conclusion 229
Reference 230
Part 3: Computational Analyses of the Cortico-Subcortical Dynamics and Parkinson’s Disease 237
Neuromodulation and Neurodynamics of Striatal Inhibitory Networks: Implications for Parkinson’s Disease 238
Introduction 239
Electrophysiology of Inhibitory Interactions Between Spiny Projection Neurons 240
Competitive Dynamics Among Spiny Projection Neurons 241
Neuromodulation of Lateral Inhibition by Dopamine and Adenosine 243
Conclusion 245
References 245
Dopaminergic Modulation of Corticostriatal Interactions and Implications for Parkinson’s Disease 249
Intrinsic Properties and Membrane Behavior of MSP Neurons 250
Computational Model 250
Functional role of MSP Cells and DA Modulation 251
Modulation Conditions 252
D1-Receptor-Mediated Modulation and Nonlinearity in the Model MSN 253
Excitatory/Inhibitory Properties of DA Modulation 254
Dopamine and Temporal Integration Properties of the MSN 256
Local and Network Level Inhibition 257
Implications of MSN Responses for BG Models 258
Implications for Parkinson’s Disease 259
References 260
Part 4: Neurobiology and Pathophysiology of Parkinson’s Disease 263
Pathogenesis of Oxidative Stress and the Destructive Cycle in the Substantia Nigra in Parkinson’s Disease 264
Fundamental Aspects of Reactive Oxygen Species 264
Can Cell Death in Substantia Nigra be Caused by Oxidative Damage? 264
Substantia Nigra is Subjected to Oxidative Stress in PD: The Destructive Toxic Cycle 267
Mitochondrial Dyisfunction and the ‘‘Toxic Cycle’’ 269
Excitotoxic Damage: Role of Glutamate 270
Neuroinflammatory Phenomena in the Substantia Nigra 271
Conclusions 272
References 272
Regulation of G-Protein-Coupled Receptor (GPCR) Trafficking in the Striatum in Parkinson’s Disease 275
Dopamine Receptor Trafficking Under Homologous Stimulation in the Striatum 276
D1R Trafficking 276
Striatal D2R Trafficking 277
Dopamine Receptor Trafficking in Parkinson’s Disease 277
Glutamate and Dopamine Receptor Trafficking Under Heterologous Stimulation 279
Conclusions 280
References 280
Atypical Parkinsonism in the French West Indies: The Plant Toxin Annonacin as a Potential Etiological Factor 284
Introduction 285
Clinical Features of the Disease Entity 285
Guadeloupean Atypical Parkinsonism Has Two Distinct Phenotypes 285
Neuroimaging Features of Atypical Parkinsonian Patients 286
Neuropathological Data 286
REM Sleep Behavior Disorder in Patients with Guadeloupean Parkinsonism 286
Candidate Etiological Factors 287
Plant Toxins 287
Other Potential Etiological Factors 287
The Complex I Inhibitor Annonacin as a Possible Etiological Factor 288
Neurodegenerative Changes Induced by Annonacin 288
Can Annonacin Intoxication Reproduce the Tau Pathology of the Disease? 289
References 290
Cognitive Deficits in Parkinson’s Disease 292
Introduction 292
Epidemiology 293
Cognitive Features in Parkinson’s Disease 294
Neuropsychiatric Symptoms in Parkinson’s Disease 295
Functional Changes Underlying Cognitive Deficits in Parkinson’s Disease 296
Genetics of PDD 297
Pathological Correlations 298
Summary and Conclusions 300
References 300
Part 5: Pharmacological and Non-Pharmacological Treatments in Parkinson’s Disease 307
Dopamine Replacement Therapy in Parkinson’s Disease: Past, Present and Future 308
L-DOPA Pharmacotherapy in Perspective 308
Current Options for a Dopaminergic Pharmacotherapy in PD 310
The Concept of Continuous Dopamine Stimulation and the Ways to Achieve It 314
Continuous Duodenal or jeujenal Infusion of l-DOPA 315
Transdermal Drug Delivery 316
‘‘Enzyme Replacement Therapy’’ by Gene Transfer 316
Neural Transplantation 317
Adjunct Treatments to Prevent or Treat Motor Complications 318
The Challenge of l-DOPA-Resistant Symptoms 320
Current Treatment Options for l-DOPA-Resistant Symptoms 322
Cognitive Dysfunction 322
Dopamine Dysregulation Syndrome and Impulse Control Disorders 322
Psychosis 322
Depression 323
Sleep 323
Autonomic Symptoms 323
L-DOPA-Resistant Gait, Freezing and Balance Problems 323
Concluding Remarks 324
References 325
Molecular, Cellular and Electrophysiological Changes Triggered by High-Frequency Stimulation of the Subthalamic Nucleus in Animal Models of Parkinson’s Disease 334
Introduction 334
Deep Brain Stimulation and Parkinson’s Disease 334
Experimental Models of Parkinson’s Disease 337
Reserpine 337
Haldol/Haloperidol 337
6-OHDA 338
MPTP 338
Electrophysiological Properties of STN Neurons 338
High-Frequency Stimulation of the STN: In Vitro Approaches 342
Electrophysiological Effects of In Vitro STN HFS 342
Other Effects of STN HFS 346
Main Contributions of In Vitro Approaches 347
High-Frequency Stimulation of the STN: In Vivo Approaches 348
Effects Ex Vivo 349
Brain Metabolism 349
Neuronal Activity and Plasticity in the STN 349
Neuronal Activity and Plasticity Outside the STN 350
Neuroprotective and Dopaminergic Effects of STN HFS 351
Electrophysiological Effects of STN HFS 352
Effects In Vivo 353
Electrophysiological Effects of STN HFS in the STN 353
Electrophysiological Effects of STN HFS Outside the STN 355
Biochemical Effects of STN HFS 360
Main Contributions of In Vivo Approaches 361
References 362
Surgical Strategies for Parkinson’s Disease Based on Animal Model Data: GPi and STN Inactivation on Various Aspects of Behavior (Motor, Cognitive and Motivational Processes) 370
Introduction 370
The Internal Globus Pallidus (GPi) 371
Motor Behavior 371
Lesion and Pharmacological Data in the Monkey 371
GPi HFS Data in the Monkey 372
Lesion Data and Pharmacological Manipulations in the Rat 372
EP HFS Data in the Rat 374
Cognitive Behavior: What Is Available in Animal Models? 374
The STN 374
Motor Behavior 375
Lesion Data in Monkeys 375
STN HFS Data in Monkeys 375
Lesion and Pharmacological Data in Rats 375
STN HFS Data in Rats 377
Cognitive Behavior 379
Lesions or STN HFS Data in Monkeys 380
Lesion Data in Rats 380
STN HFS Data in Rats 382
Motivational Behavior and Psychiatric Models 384
Conclusion 386
References 386
Antidromic Cortical Activity as the Source of Therapeutic Actions of Deep Brain Stimulation 391
Introduction 391
A Direct Test of the Idea in Anaesthetised Animals 392
Some Experiments on Alert Animals 395
Resonance as the Explanation for Frequency Dependence 396
Some Suggestions for Future Work 398
References 399
Cell-Based Replacement Therapies for Parkinson’s Disease 402
Introduction 402
Grafts Based on Cells of the Sympathoadrenal Cell Lineage 404
Sympathetic Neurons 405
Adrenal Chromaffin Cells 406
Extra-Adrenal Chromaffin Cells 408
Advantages of Transplanting SA Lineage Cells 411
Carotid Body Dopamine Cells 411
Fetal Mesencephalic Neurons 412
Stem Cells 414
Generation of DA Neurons from VM Neural Stem/Progenitor Cells (NSC/NP) 415
Generation of DA Neurons from Other NSCs 415
Generation of DA Neurons from Embryonic Stem Cells (ESCs) 416
Neural Xenotransplantation 418
Genetically Engineered Autologous Tissue 419
Retinal Pigmental Epithelial Cells 419
References 420
Index 429