Groenewegen / Voorn / Berendse The Basal Ganglia IX

1. Auflage 2009
ISBN: 978-1-4419-0340-2
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 58, 608 Seiten

Reihe: Advances in Behavioral Biology

The aim of the International Basal Ganglia Society (IBAGS) is to further our understanding of normal basal ganglia function and the pathophysiology of disorders of the basal ganglia, including Parkinson's disease, Huntington's disease, and schizophrenia. Each triennial meeting of IBAGS brings together basic research scientists from all disciplines as well as clinicians who are actively involved in the treatment of basal ganglia disorders, to discuss the most recent advances in the field and to generate new approaches and ideas for the future. This volume comprises the proceedings of the 9th meeting of IBAGS, held in Egmond aan Zee, The Netherlands, September 2nd-6th, 2007.

Autoren/Hrsg.

Groenewegen, Hendrik Jan

Voorn, Pieter

Berendse, Henk W.

Mulder, Antonius B.

Cools, Alexander R.

Inhaltsverzeichnis

1;Preface;5
2;Contents;9
3;You Cannot Have a Vertebrate Brain Without a Basal Ganglia;26
3.1;1 Introduction;27
3.2;2 Where is the Basal Ganglia in Nonmammals?;28
3.3;3 By What Pathways Does the Basal Ganglia Control Movement in Nonmammals;38
3.4;4 Major Evolutionary Steps in Basal Ganglia Organization;42
3.5;References;43
4;The Involvement of Corticostriatal Loops in Learning Across Tasks, Species, and Methodologies;48
4.1;1 Introduction;48
4.2;2 Basal-Ganglia-Dependent Learning Tasks;49
4.2.1;2.1 Tasks from the Rodent Literature;49
4.2.1.1;2.1.1 Instrumental Conditioning;49
4.2.2;2.2 Tasks from the Monkey Literature;50
4.2.2.1;2.2.1 Visual Discrimination;50
4.2.2.2;2.2.2 Arbitrary Visuomotor Learning/Conditional Response;50
4.2.2.3;2.2.3 Rule Learning;51
4.2.3;2.3 Tasks from the Human Literature;51
4.2.3.1;2.3.1 Categorization and Classification;51
4.2.3.2;2.3.2 Decision Making;52
4.3;3 Roles of Corticostriatal Loops in Learning;52
4.3.1;3.1 Corticostriatal Loops: Anatomy;53
4.3.2;3.2 Corticostriatal Loops: Function;54
4.3.3;3.3 Visual Corticostriatal Loop;55
4.3.4;3.4 Motor Corticostriatal Loop;56
4.3.5;3.5 Executive Corticostriatal Loop;57
4.3.6;3.6 Motivational Corticostriatal Loop;58
4.4;4 Interactions between Corticostriatal Loops;58
4.5;References;59
5;Information Processing in the Striatum of Behaving Monkeys;63
5.1;1 Introduction;63
5.2;2 Methods;64
5.3;3 Results;65
5.4;4 Discussion;67
5.5;References;69
6;What Controls the Timing of Striatal Spiny Cell Action Potentials in the Up State?;71
6.1;1 Up and Down States;71
6.2;2 What Kind of Synaptic Input Could Trigger Spiking in the Up State?;72
6.3;3 A Role for Inhibition?;73
6.4;4 Measurement of Excitatory and Inhibitory Conductances in the Up State;74
6.5;5 Fast Membrane Fluctuations Are Mostly Inhibitory;77
6.6;References;82
7;Asymmetric Encoding of Positive and Negative Expectations by Low-Frequency Discharge Basal Ganglia Neurons;84
7.1;1 Introduction;84
7.2;2 Methods;86
7.3;3 Results;86
7.3.1;3.1 Monkey Behavior Reflects Expectation of Rewarding and Aversive Events;86
7.3.2;3.2 PANs and GPe LFD Activity Are Asymmetrically Modulated by Expectation of Aversive and Reward Outcomes;88
7.4;4 Discussion;90
7.5;References;92
8;Stimulation Effect on Neuronal Activity in the Globus Pallidus of the Behaving Macaque;94
8.1;1 Introduction;94
8.2;2 Methods;95
8.3;3 Results;96
8.4;4 Discussion;101
8.5;References;103
9;High-Frequency Stimulation of the Globus Pallidus External Segment Biases Behavior Toward Reward;105
9.1;1 Introduction;105
9.2;2 Methods;107
9.2.1;2.1 General;107
9.2.2;2.2 Behavioral Task;107
9.2.3;2.3 Data Analysis;109
9.3;3 Results;110
9.3.1;3.1 High-Frequency Stimulation Changes the Monkey’s Licking Response;110
9.3.2;3.2 Progression of the Stimulation Effect;112
9.4;4 Discussion;113
9.4.1;4.1 High-Frequency Stimulation Alters Expectation of Reward;113
9.4.2;4.2 High-Frequency Stimulation is Associated with Synaptic Plasticity;113
9.4.3;4.3 Therapeutic Implications;114
9.5;References;114
10;The Subthalamic Region of Luys, Forel, and Dejerine;117
10.1;1 Introduction;117
10.2;2 Research by Luys on Brain structure;118
10.2.1;2.1 Brain Atlases;118
10.2.2;2.2 Methods of Preparation;118
10.2.3;2.3 The Subthalamic Region in the Atlases;118
10.3;3 Research by Luys on Brain Functions;120
10.3.1;3.1 Neurology;120
10.3.2;3.2 Psychiatry;121
10.3.3;3.3 Hypnotism and Other Psychic Phenomena;122
10.4;4 The Subthalamus Following Luys;123
10.4.1;4.1 Meynert;123
10.4.2;4.2 Auguste Forel (1848–1931);123
10.4.3;4.3 Joseph-Jules Dejerine (1849–1917);124
10.5;5 Conclusions;126
10.5.1;5.1 Luys as Discoverer of the STN;126
10.5.2;5.2 Establishment of Basic Subthalamic Structure;126
10.6;References;126
11;Organization of Motor Cortical Inputs to the Subthalamic Nucleus in the Monkey;128
11.1;1 Introduction;129
11.2;2 Methods;129
11.3;3 Results;130
11.4;4 Discussion;134
11.5;References;135
12;A Subpopulation of Mesencephalic Dopamine Neurons Interfaces the Shell of Nucleus Accumbens and the Dorsolateral Striatum in ;137
12.1;1 Introduction;138
12.2;2 Materials and Methods;139
12.2.1;2.1 Anatomical Tracing Studies;139
12.2.1.1;2.1.1 Surgical Procedures;139
12.2.1.2;2.1.2 Tracer Injections;139
12.2.1.3;2.1.3 Histological Procedures;139
12.2.2;2.2 Electrophysiological Studies;140
12.3;3 Results;141
12.3.1;3.1 Anatomical Tracing Studies;141
12.3.2;3.2 Effect of Shell Stimulation on the Activity of VTA/SNC Dopaminergic Neurons Projecting to the Sensorimotor Territory of th;143
12.4;4 Discussion;143
12.4.1;4.1 Mesencephalic Dopamine Neurons as a Link Between the Shell and the Dorsolateral Striatum;145
12.4.2;4.2 Functional Considerations;146
12.4.3;4.3 Conclusion;147
12.5;References;147
13;Synchrony of the Rat Medial Prefrontal Cortex Network During Isoflurane Anaesthesia;149
13.1;1 Introduction;149
13.2;2 Materials and Methods;151
13.2.1;2.1 Surgery and Placement;151
13.2.2;2.2 Isoflurane Manipulations;151
13.2.3;2.3 Data Acquisition and Analysis;152
13.2.4;2.4 Histological Evaluation;152
13.3;3 Results;152
13.3.1;3.1 Definition of Up- and Down-States;152
13.3.2;3.2 Up- and Down-State Transitions are Reversibly Influenced by Isoflurane Anaesthesia;153
13.3.3;3.3 Prelimbic Neurons Fire Action Potentials Only During Up-States;154
13.4;4 Discussion;155
13.4.1;4.1 Synaptic Effects of Isoflurane;156
13.4.2;4.2 Isoflurane Modulates Mechanisms Underlying Up-Down-State Transitions;157
13.4.3;4.3 Final Considerations;158
13.5;References;158
14;On the Relationships Between the Pedunculopontine Tegmental Nucleus, Corticostriatal Architecture, and the Medial Reticular Fo;161
14.1;1 The Pedunculopontine Tegmental Nucleus;162
14.2;2 How does the PPTg Interact with the Anatomy of Corticostriatal Loops?;162
14.3;3 Corticostriatal Systems, Instrumental Responding and the PPTg;165
14.4;4 Does PPTg Integrate Processing Between Corticostriatal and Brainstem Systems?;169
14.5;5 Conclusions;171
14.6;References;172
15;Microcircuits of the Pedunculopontine Nucleus;176
15.1;1 Past and Present Notions of the PPN;176
15.2;2 Ultrastructural Analysis;177
15.3;3 Local Connectivity;178
15.4;4 Local Network Model;179
15.5;References;181
16;The Effects of Dopaminergic Modulation on Afferent Input Integration in the Ventral Striatal Medium Spiny Neuron;184
16.1;1 Introduction;184
16.2;2 Striatal Anatomy;185
16.2.1;2.1 Anatomy of the Nucleus Accumbens;185
16.3;3 Functional Role of MSP Cells and DA Modulation;187
16.3.1;3.1 Intrinsic Properties and Membrane Behavior of MSP Neurons;188
16.4;4 Computational Model;189
16.4.1;4.1 Current Injection Responses;190
16.4.2;4.2 Synaptic Input Responses;193
16.5;5 Bistability or Bimodality?;196
16.5.1;5.1 Effect of NMDA:AMPA Ratio Changes;197
16.5.2;5.2 Local Inhibition;200
16.6;6 Afferent Ensembles and Integration;200
16.7;7 Implications of the Model for Disease States;201
16.8;References;202
17;A Spiking Neuron Model of the Basal Ganglia Circuitry that Can Generate Behavioral Variability;206
17.1;1 Introduction;206
17.2;2 Computational Hypotheses for Basal Ganglia Function;207
17.3;3 Simulation Results;209
17.3.1;3.1 Selection and Timing Mechanisms for Exploration in the Basal Ganglia Network;210
17.3.2;3.2 Modulation of Selection Probability and Timing for Exploitation;213
17.4;4 Discussion;214
17.5;References;214
18;Learning with an Asymmetric Teacher: Asymmetric Dopamine-Like Response Can Be Used as an Error Signal for Reinforcement Learn;216
18.1;1 Introduction;217
18.1.1;1.1 Reinforcement Learning and the Basal Ganglia;217
18.1.2;1.2 Dopaminergic Signal Is Truncated at Zero;218
18.2;2 Methods;219
18.3;3 Results;222
18.3.1;3.1 Error Signal with Lower Gain for the Negative Domain;222
18.3.2;3.2 Error Signal with a Constant Negative Value for the Negative Domain;223
18.3.3;3.3 Error Signal Set to Zero for the Negative Domain;223
18.4;4 Discussion;223
18.5;References;225
19;A Theoretical Information Processing-Based Approach to Basal Ganglia Function;226
19.1;1 Introduction;226
19.2;2 The Functional Perspective;228
19.3;3 The Neurophysiologic Basis;229
19.4;4 The Informational Theoretical Construct;230
19.4.1;4.1 Ionic Mechanisms;231
19.4.2;4.2 Application to Behavior;232
19.5;5 Can We Make Any Real Sense of This?;233
19.6;References;237
20;The Cellular Localisation of GABAA and Glycine Receptors in the Human Basal Ganglia;239
20.1;1 Introduction;239
20.2;2 Methods;240
20.2.1;2.1 Brain Tissue;240
20.2.2;2.2 Immunohistochemical Procedures;240
20.2.2.1;2.2.1 Primary Antibodies;240
20.2.2.2;2.2.2 Single Immunoperoxidase Labelling;241
20.2.2.3;2.2.3 Immunofluorescent Double Labelling;242
20.3;3 Results;242
20.3.1;3.1 Striatum;242
20.3.2;3.2 Globus Pallidus;245
20.3.3;3.3 Lateral Medullary Lamina and Medial Medullary Lamina;245
20.3.4;3.4 Substantia Nigra;245
20.3.4.1;3.4.1 Substantia Nigra Pars Compacta;245
20.3.4.2;3.4.2 Substantia Nigra Pars Reticulata;246
20.4;4 Discussion;246
20.4.1;4.1 Striatum;246
20.4.2;4.2 Globus Pallidus;247
20.4.3;4.3 Substantia Nigra;248
20.4.4;4.4 Functional Considerations;249
20.5;References;249
21;Comparative Ultrastructural Analysis of D1 and D5 Dopamine Receptor Distribution in the Substantia Nigra and Globus Pallidus ;252
21.1;1 Introduction;253
21.2;2 Materials and Methods;254
21.2.1;2.1 Animals;254
21.2.2;2.2 MPTP Administration and Behavioral Assessment;254
21.2.3;2.3 Tissue Preparation;254
21.2.4;2.4 Primary Antisera;254
21.2.5;2.5 Immunoperoxidase Procedure;255
21.2.6;2.6 Immunogold Procedure;255
21.2.7;2.7 Ultrastructural Analysis;256
21.3;3 Results;256
21.3.1;3.1 Ultrastructural Localization of D1 Receptor Immunoreactivity in GPi and SNr;256
21.3.2;3.2 Ultrastructural Localization of D5 Receptor Immunoreactivity in GPi and SNr;258
21.4;4 Discussion;260
21.4.1;4.1 Localization of D1/D5 Receptors in GPi and SNr;260
21.4.2;4.2 Functional Consequences of Dopamine D1/D5 Receptor Activation;260
21.4.3;4.3 Dopamine D1/D5 Receptor Activation May Influence Behavior;261
21.4.4;4.4 Functional Significance of D1LRs-Mediated Effects in Parkinsonism;262
21.5;References;263
22;Motor-Skill Learning in a Novel Running-Wheel Paradigm: Long-Term Memory Consolidated by D1 Receptors in the Striatum;267
22.1;1 Introduction;267
22.2;2 Motor-Skill Learning in the Running Wheel;269
22.2.1;2.1 Wheel-Skill Training and Test;269
22.2.2;2.2 Practice is Essential for Wheel-Skill Learning;269
22.2.3;2.3 Wheel-Skill Memory Lasts for Months;270
22.2.4;2.4 Effects of Cocaine and D1 Receptor Stimulation in the Striatum on Wheel-Skill Learning;271
22.2.5;2.5 Critical Role for Striatum in Wheel-Skill Consolidation and Stabilizing Effects of Cocaine;273
22.3;3 Discussion;275
22.3.1;3.1 Wheel-Skill Learning;275
22.3.2;3.2 Role of Striatal D1 Receptors and Effects of Cocaine on Skill Consolidation;276
22.3.3;3.3 Dissociation of Early- and Late-Stage Long-Term Skill Memory;277
22.4;References;278
23;Discriminative Stimulus- vs. Conditioned Reinforcer-Induced Reinstatement of Drug-Seeking Behavior and arc mRNA Expression i;280
23.1;1 Introduction;280
23.1.1;1.1 Neural Substrates Mediating the Effects of Conditioned Stimuli on Reinstatement;281
23.1.2;1.2 Cellular Compartment Analysis of Temporal Activity by Fluorescence In Situ Hybridization;282
23.2;2 Materials and Methods;283
23.2.1;2.1 Subjects;283
23.2.2;2.2 Surgical Procedure;283
23.2.3;2.3 Cocaine Self-Administration Training;284
23.2.3.1;2.3.1 DS Self-Administration Training;284
23.2.3.2;2.3.2 CR Self-Administration Training;284
23.2.3.3;2.3.3 Extinction Training;285
23.2.3.4;2.3.4 Reinstatement Test Day;285
23.2.4;2.4 In Situ Hybridization;285
23.2.5;2.5 Imaging and Cellular Compartment Analysis of Gene Expression;286
23.3;3 Results;286
23.3.1;3.1 Rats Can be Trained to Self-Administer Cocaine Under the Dual DS/CR Paradigm;286
23.3.2;3.2 Rats Trained Under Dual Paradigm Conditions Exhibit Cue-Induced Reinstatement of Drug-Seeking Behavior;287
23.3.3;3.3 Cellular Compartment Analysis of arc mRNA Expression in Neurons of Dorsolateral Striatum;287
23.3.4;3.4 Arc mRNA Expression Was Correlated with Cue-Induced Reinstatement of Drug-Seeking Behavior;289
23.4;4 Discussion;291
23.5;References;294
24;Preferential Modulation of the GABAergic vs. Dopaminergic Function in the Substantia Nigra by 5-HT2C Receptor;296
24.1;1 Introduction;296
24.2;2 Serotonin2C Receptor Distribution Within the Basal Ganglia Nuclei;297
24.2.1;2.1 Serotonin2c Receptor Distribution Within the Substantia Nigra;298
24.2.2;2.2 Serotonin2c Receptor Regulation in PD;298
24.3;3 Serotonin2C Modulation of the Substantia Nigra;299
24.3.1;3.1 Electrophysiological Data;299
24.3.1.1;3.1.1 Substantia Nigra Pars Compacta;299
24.3.1.2;3.1.2 Substantia Nigra Pars Reticulata;299
24.3.2;3.2 Neurochemical Data;302
24.3.2.1;3.2.1 Striatum;302
24.3.2.2;3.2.2 Substantia Nigra Pars Reticulata;302
24.4;4 Conclusions;303
24.5;References;305
25;Blockade of GABA Transporter (GAT-1) Modulates the GABAergic Transmission in the Rat Globus Pallidus;308
25.1;1 Introduction;308
25.2;2 Material and Methods;309
25.2.1;2.1 Electron Microscopic Immunocytochemistry;309
25.2.2;2.2 Whole-Cell Patch Clamp Recording;310
25.3;3 Results;311
25.3.1;3.1 Expression of GAT-1 in the GP;311
25.3.2;3.2 Effects of GAT-1 Transporter Inhibitor on Evoked IPSCs in the GP;311
25.3.2.1;3.2.1 Parasagittal Striatopallidal Slice Preparation;311
25.3.2.2;3.2.2 Coronal Striatopallidal Slice Preparation;312
25.3.3;3.3 Blockade of GAT-1 Has No Effect on mIPSCs;314
25.4;4 Discussion;315
25.5;References;317
26;Nitric Oxide Modulation of the Dopaminergic Nigrostriatal System: Focus on Nicotine Action;319
26.1;1 Introduction;319
26.2;2 Nitric Oxide Distribution in the Basal Ganglia;320
26.3;3 Involvement of NO in Neurodegeneration of Dopaminergic Nigrostriatal System;322
26.4;4 Nitric Oxide Modulation of the Activity of Dopaminergic Nigrostriatal System;323
26.5;5 NO/DA Interaction: Focus on Nicotine Effect;324
26.5.1;5.1 Experimental Data;324
26.5.2;5.2 Discussion;327
26.6;6 Conclusions;328
26.7;References;329
27;Regulation of Dopamine Release by Striatal Acetylcholine and Nicotine Is via Distinct Nicotinic Acetylcholine Receptors in Dor;332
27.1;1 Introduction;332
27.2;2 Materials and Methods;334
27.2.1;2.1 Slice Preparation and Voltammetry;334
27.2.2;2.2 Electrical Stimulation;334
27.2.3;2.3 Experimental Design and Analysis;335
27.3;3 Results;335
27.3.1;3.1 Identification of Different nAChR Subtypes in CPu and NAc;335
27.3.2;3.2 a6b2*-nAChRs Can Account for All Frequency Filtering of DA Release by nAChRs in NAc but Not CPu;335
27.3.3;3.3 Regional Differences in a6-nAChR Function Are Not Due to Confounding Differences in Endogenous ACh Tone or DA Rele;338
27.4;4 Discussion;339
27.4.1;4.1 b2*-nAChRs and Their Subtypes: A Filter on DA Release Probability in CPu and NAc;339
27.4.2;4.2 Dominant Role for a6 Subunit in NAc but Not CPu;340
27.5;5 Conclusions;341
27.6;References;341
28;Nitrergic Tone Influences Activity of Both Ventral Striatum Projection Neurons and Interneurons;345
28.1;1 Introduction;345
28.2;2 Materials and Methods;346
28.2.1;2.1 Animal Preparation;346
28.2.2;2.2 Microelectrodes and PFC Activation;346
28.2.3;2.3 Electrophysiological Recordings and Microiontophoresis;347
28.2.4;2.4 Juxtacellular Labelling and Histochemistry of Single Neurons;348
28.3;3 Results;349
28.3.1;3.1 Effects of the NO Manipulation VST Neurons;349
28.3.2;3.2 Anatomical Identification of Neurons;350
28.4;4 Discussion;350
28.4.1;4.1 Modulation of Striatal Activity by Alterations of Nitrergic Tone;350
28.4.2;4.2 Nitrergic Modulation of VST Interneurons;353
28.5;References;354
29;Kainic Acid-Induced Cell Proliferation in the Striatum Is Not Estrogen Dependent;357
29.1;1 Introduction;357
29.1.1;1.1 Organization of the Subventricular Zone in the Adult Mammalian Nervous System;358
29.1.2;1.2 The Role of Estrogen in Adult Neurogenesis;358
29.2;2 Methods;360
29.3;3 Results;361
29.4;4 Discussion;362
29.5;References;364
30;Striatal Dopaminergic Denervation and Spine Loss in MPTP-Treated Monkeys;366
30.1;1 Introduction;366
30.2;2 Materials and Methods;367
30.2.1;2.1 Animals and Tissue Preparation;367
30.2.1.1;2.1.1 MPTP Injections and Parkinsonism;367
30.2.1.2;2.1.2 Animal Perfusion;368
30.2.2;2.2 Golgi Impregnation;368
30.2.3;2.3 Immunocytochemistry;368
30.2.3.1;2.3.1 Primary Antibodies;368
30.2.3.2;2.3.2 Immunoperoxidase Labeling for Light and Electron Microscopy;368
30.2.4;2.4 Data Analysis;369
30.2.4.1;2.4.1 Quantitative Analysis of Dendritic Spine Density in Golgi-Impregnated Neurons;369
30.2.4.2;2.4.2 Immunolabeled Spine Analysis;369
30.2.4.3;2.4.3 Statistical Analysis and Photomicrograph Production;369
30.3;3 Results;370
30.3.1;3.1 Striatal Spine Loss: Golgi Analysis;370
30.3.1.1;3.1.1 Severely Dopamine-Depleted Striatum;370
30.3.1.2;3.1.2 Partially Dopamine-Depleted Striatum;370
30.3.2;3.2 Density of D1-Immunoreactive Spines in the Striatum;370
30.3.3;3.3 Calbindin Immunolabeling in the Striatum;372
30.4;4 Discussion;376
30.5;References;378
31;Prevention of Calbindin Recruitment into Nigral Dopamine Neurons from MPTP-Induced Degeneration in Macaca fascicularis;381
31.1;1 Introduction;381
31.2;2 Methods;382
31.2.1;2.1 Animals;382
31.2.2;2.2 Surgical Procedures;382
31.2.3;2.3 MPTP Treatment;384
31.2.4;2.4 Behavioral Analysis;384
31.2.5;2.5 Immunohistochemistry;384
31.2.6;2.6 Histological Analysis;385
31.3;3 Results;385
31.4;4 Discussion;386
31.5;References;387
32;Changes in the Subcellular Localization and Functions of GABA-B Receptors in the Globus Pallidus of MPTP-Treated Monkeys;390
32.1;1 Introduction;390
32.2;2 Materials and Methods;392
32.2.1;2.1 Animals and MPTP Treatment;392
32.2.2;2.2 Immunohistochemical Localization of GABA-B Receptors;392
32.2.3;2.3 Local Administration of GABA-B Compounds and Extracellular Recording of Pallidal Units;393
32.2.3.1;2.3.1 Surgery;393
32.2.3.2;2.3.2 Recording and Injection Sessions;393
32.2.3.3;2.3.3 Drugs;394
32.2.3.4;2.3.4 Data Analysis;394
32.3;3 Results;394
32.4;4 Summary and Conclusions;397
32.4.1;4.1 Effects of Dopaminergic Depletion on GABA-B Receptor Expression in the GP;397
32.4.2;4.2 Pharmacological Activation and Blockade of GABA-B Receptors in GPe and GPi of Parkinsonian Monkeys;398
32.5;References;398
33;Morphogenesis of Rodent Neostriatum Following Early Developmental Dopamine Depletion;401
33.1;1 Introduction;401
33.2;2 Methods;403
33.3;3 Results;404
33.4;4 Discussion and Perspectives;406
33.4.1;4.1 Neostriatal DA Afferents in ak Mice Are Reduced in a Dorsal to Ventral Manner;408
33.4.2;4.2 Reduced Neostriatal DA Afferents in ak Mice Reduce Patchy MOR Expression;409
33.4.3;4.3 Developmental Dopamine Depletion in ak Mice Does Not Alter Neostriatal Neuron Numbers but Reduces Neostriatal Volume and ;410
33.5;References;410
34;Upregulation of NAD(P)H:Quinone Oxidoreductase (NQO1) in Glial Cells of 6-Hydroxydopamine-Lesioned Substantia Nigra in the Rat;413
34.1;1 Introduction;414
34.2;2 Materials and Methods;415
34.2.1;2.1 Animals;415
34.2.2;2.2 Intracerebral Injections of 6-Hydroxydopamine;415
34.2.3;2.3 Immunohistochemistry;415
34.2.4;2.4 LY 83583-Mediated Enzyme Histochemistry;416
34.2.5;2.5 Fluorojade Histochemistry;416
34.2.6;2.6 Digital Images;416
34.3;3 Results;417
34.3.1;3.1 Degeneration Pattern of DA Neurons After 6-OHDA Administration;417
34.3.2;3.2 Fluorojade-B;417
34.3.3;3.3 Autofluorescence;418
34.3.4;3.4 Activation of Microglia;419
34.3.5;3.5 Upregulation of NQO1 Immunoreactivity and NQO1 Enzyme Activity in Glial Cells;420
34.3.6;3.6 Induction of Reactive Glial Cells and Upregulation of GFAP Immunoreactivity in Reactive Glial Cells;425
34.3.7;3.7 Comparison of the Temporal Patterns of the Stainings Used;425
34.4;4 Discussion;426
34.5;References;430
35;Clioquinol Protects Against Cell Death in Parkinson’s Disease Models In Vivo and In Vitro;432
35.1;1 Introduction;432
35.2;2 Methods;433
35.2.1;2.1 Mice;433
35.2.2;2.2 6-OHDA Toxin Lesioning;434
35.2.3;2.3 Clioquinol Feeding;434
35.2.4;2.4 Histology, Estimation of Lesion Size and Stereological Cell Counts;434
35.2.5;2.5 MTT Assay for Determination of Human Neuroblastoma M17 Cell Viability;435
35.3;3 Results;435
35.3.1;3.1 Effects of CQ on Mice Lesioned with 6-OHDA;435
35.3.2;3.2 Effects of DA, Metals and CQ in an In Vitro Cellular Model;436
35.4;4 Discussion;438
35.5;References;441
36;Oscillatory Activity and Synchronization in the Basal Ganglia Network in Rodent Models of Parkinson’s Disease;444
36.1;1 Introduction;444
36.2;2 Results;447
36.2.1;2.1 Beta Frequency Activity in Paired GP-STN Recordings: Firing Rate and Pattern;447
36.2.2;2.2 Beta Frequency Activity in Paired GP–STN Recordings: LFP Power;449
36.2.3;2.3 Beta Frequency Activity in Paired GP–STN Recordings: Coherence and Spike–Triggered LFP Waveforms;449
36.3;3 Discussion;452
36.3.1;3.1 Loss of Dopamine and Emergence of Synchronized Activity in Basal Ganglia;452
36.3.2;3.2 Beta Activity in Additional Awake Rodent Models of PD;454
36.3.3;3.3 Observations in Rodent Models Consistent with Changes Observed in PD Patients: Conclusions;455
36.4;References;456
37;Behavioural Correlates of Dopaminergic Agonists’ Dyskinetic Potential in the 6-OHDA-Lesioned Rat;461
37.1;1 Introduction;461
37.2;2 Experimental Procedures;463
37.2.1;2.1 Subjects and 6-OHDA Lesion;463
37.2.2;2.2 Drugs;463
37.2.3;2.3 Assessment of Nigrostriatal Lesion: Adjusting Steps and Cylinder Test;463
37.2.4;2.4 Drug Treatment and Behavioural Tests;464
37.2.5;2.5 Statistics;464
37.3;3 Results;464
37.4;4 Discussion;466
37.4.1;4.1 High Dyskinetic Response After D1 Receptor Stimulation by SKF38393;467
37.4.2;4.2 Low Dyskinetic Response After D2 Receptor Stimulation by Ropinirole;467
37.5;5 Conclusions;468
37.6;References;468
38;Basal Ganglia and Behaviour: Behavioural Effects of Deep Brain Stimulation in Experimental Neurological and Psychiatric Disor;471
38.1;1 Introduction;471
38.2;2 Deep Brain Stimulation for Non-motor Symptoms of Movement Disorders;472
38.3;3 Deep Brain Stimulation in Psychiatric Disorders;476
38.3.1;3.1 Obsessive-Compulsive Disorder;476
38.3.2;3.2 Animal Models of Depression;477
38.3.3;3.3 Animal Models of Panic Disorder;478
38.4;4 Discussion;478
38.5;References;480
39;Modeling Nonmotor Symptoms of Parkinson’s Disease in Genetic Mouse Models;483
39.1;1 Introduction;483
39.2;2 Thy1-aSyn Mice;484
39.2.1;2.1 Neuropathological Alterations in Thy1-aSyn Mice;484
39.2.2;2.2 Nonmotor Deficits in Thy1-aSyn Mice;485
39.2.2.1;2.2.1 Olfactory Deficits;485
39.2.2.2;2.2.2 Anomalies in Circadian Rhythm;486
39.2.2.3;2.2.3 Anxiety and Depression;486
39.2.2.4;2.2.4 Cognitive Deficits;486
39.2.2.5;2.2.5 Gastrointestinal Dysfunction;487
39.2.2.6;2.2.6 Cardiovascular Dysfunction;487
39.2.3;2.3 Progressive Sensorimotor Dysfunction in Thy1-aSyn Mice;487
39.3;3 Conclusion;488
39.4;References;489
40;Differential Expression of Doublecortin-Like Kinase Gene Products in the Striatum of Behaviorally Hyperresponsive Rats;492
40.1;1 Introduction;493
40.2;2 Materials and Methods;494
40.2.1;2.1 Animals and Tissue Preparation;494
40.2.2;2.2 Unilateral Depletion of Dopamine and Exposure to Dopamine Agonists;495
40.2.3;2.3 Psychomotor Sensitization to Amphetamine or Morphine;495
40.2.4;2.4 Tyrosine Hydroxylase Immunostaining;496
40.2.5;2.5 In Situ Hybridization;496
40.2.6;2.6 Measurements and Quantifications;496
40.3;3 Results;497
40.3.1;3.1 Extent and Effect of the 6-OHDA Lesions;497
40.3.2;3.2 Changes in Levels of DCLK mRNA;497
40.3.3;3.3 Changes in Levels of CARP mRNA;499
40.4;4 Discussion;501
40.4.1;4.1 Apoptosis;502
40.4.2;4.2 Neuronal Morphology;503
40.4.3;4.3 Mechanisms;504
40.4.4;5 Conclusions;505
40.5;References;506
41;Paradox of the Basal Ganglia Model: The Antidyskinetic Effect of Surgical Lesions in Movement Disorders;511
41.1;1 Introduction;511
41.2;2 Pallidotomy in Parkinson’s Disease: Summary of Clinical Effects;512
41.3;3 Pallidotomy and Dyskinesias;513
41.4;4 The First Paradox of the Basal Ganglia Model: How Does Pallidotomy Eliminate Dyskinesias?;513
41.5;5 Conclusions;516
41.6;References;516
42;The Dynamic Relationship Between Voluntary and Involuntary Motor Behaviours in Patients with Basal Ganglia Disorders;519
42.1;1 Introduction;520
42.1.1;1.1 The Problem of Recording Whole-Body Involuntary Motor Behaviours;520
42.1.2;1.2 The Problem of Recording ‘Core’ Bradykinesia;521
42.1.3;1.3 The Dynamic Relationship Between Involuntary and Voluntary Motor Behaviours in Patients with PD Having LID and in Patien;522
42.2;2 Methods;523
42.2.1;2.1 Participants;523
42.2.2;2.2 Whole-Body Involuntary Movements Quantification;523
42.2.3;2.3 Bradykinesia Quantification Using a Rapid Alternating Movements Task;524
42.2.4;2.4 Statistics;524
42.3;3 Results;524
42.3.1;3.1 Whole-Body Involuntary Movements;524
42.3.2;3.2 Rapid Alternating Movement;526
42.4;4 Discussion;527
42.4.1;4.1 The Bradykinesia Issue in HD;527
42.4.2;4.2 Implications of the Present Results for Basal Ganglia Pathophysiology;527
42.4.3;4.3 Clinical Implications of the Present Results;529
42.5;5 Conclusions;530
42.6;References;530
43;Reduced and Modified Neuronal Activity in the Subthalamic Nucleus of Parkinson’s Disease Patients with Prior Pallidotomy;533
43.1;1 Introduction;533
43.2;2 Methods;535
43.2.1;2.1 Patients;535
43.2.2;2.2 Data Acquisition and Analysis;536
43.2.3;2.3 The Root Mean Square: An STN Raw Activity Measure;536
43.2.4;2.4 The Mean Successive Difference: A Measure of Irregularity;537
43.2.5;2.5 Statistical Analysis;538
43.2.6;2.6 Spectral Analysis;538
43.2.7;2.7 Software;538
43.3;3 Results;539
43.3.1;3.1 Average Normalized RMS;539
43.3.2;3.2 Variance of Normalized RMS;540
43.3.3;3.3 Irregularity (MSD) of Normalized RMS;540
43.3.4;3.4 Ipsilateral vs. Contralateral STN Activity in Cases with Unilateral Pallidotomy;540
43.3.5;3.5 Spectral Analysis;541
43.4;4 Discussion;541
43.5;5 Conclusions;544
43.6;References;545
44;Inhibition of Neuronal Firing in the Human Substantia Nigra Pars Reticulata in Response to High-Frequency Microstimulation Aid;548
44.1;1 Introduction;549
44.1.1;1.1 Parkinson’s Disease and the Basal Ganglia;549
44.1.2;1.2 Effects of High-Frequency Stimulation;549
44.2;2 Methods;550
44.2.1;2.1 Surgery and Recordings;550
44.2.2;2.2 Analysis;551
44.3;3 Results;552
44.4;4 Discussion;554
44.4.1;4.1 SNr Inhibition;554
44.4.2;4.2 STN Inhibition;555
44.4.3;4.3 Determining STN Borders;556
44.5;5 Conclusion;557
44.6;References;557
45;Activity of Thalamic Ventralis Oralis Neurons in Rigid-Type Parkinson’s Disease;559
45.1;1 Introduction;559
45.2;2 Subjects and Methods;560
45.3;3 Results;562
45.4;4 Discussion;563
45.5;References;566
46;Motor and Non-motor Effects of PPN-DBS in PD Patients: Insights from Intra-operative Electrophysiology;568
46.1;1 Introduction;569
46.2;2 Methods;570
46.2.1;2.1 Neurosurgery;570
46.2.2;2.2 Patient Evaluation;570
46.2.3;2.3 Peri-operative Recordings;572
46.3;3 Results;573
46.3.1;3.1 Acute and Long-Lasting Motor Effect;573
46.3.2;3.2 Cognitive Effects;574
46.3.3;3.3 Effects on Sleep;574
46.3.4;3.4 Effects of PPN-DBS on STN Neurons;575
46.4;4 Discussion;576
46.4.1;4.1 Motor Effects;576
46.4.2;4.2 Non-motor Effects;577
46.5;5 Conclusions;578
46.5.1;5.1 Is PPN-DBS (at 10–25 Hz in Our Protocol) Re-activating Impaired Pathways?;578
46.5.2;5.2 Is PPN-DBS Mostly Affecting Non-motor and Not Strictly Dopamine-Centred Functions?;579
46.6;References;580
47;Observation of Involuntary Movements Through Clinical Effects of Surgical Treatments;583
47.1;1 Introduction;583
47.2;2 Methods;584
47.2.1;2.1 Subjects;584
47.2.2;2.2 Surgery;584
47.2.3;2.3 Stereotactic Targets;584
47.2.4;2.4 EMG Analysis;584
47.3;3 Results;585
47.3.1;3.1 Tremor;585
47.3.1.1;3.1.1 Essential Tremor;585
47.3.1.2;3.1.2 Multiple Sclerosis;585
47.3.2;3.2 Dystonia;585
47.3.2.1;3.2.1 Generalized Dystonia;585
47.3.2.2;3.2.2 Focal Dystonia;586
47.3.3;3.3 Choreoballistic Involuntary Movements;586
47.4;4 Discussion;587
47.5;5 Conclusions;589
47.6;References;589