Basic Neurochemistry. Molecular, Cellular and Medical Aspects

Basic NeuroChemistry: Molecular, Cellular and Medical Aspects 7th
......Page 1
Contents......Page 3
Section Editors......Page 7
Contributors......Page 8
Acknowledgments and History......Page 16
Preface to the Seventh Edition......Page 18
Pierre Morell, Ph.D. 1941–2003......Page 20
Cellular Neurochemistry and Neural Membranes......Page 22
UNDERSTANDING NEUROANATOMY IS NECESSARY TO STUDY NEUROCHEMISTRY......Page 23
CHARACTERISTICS OF THE NEURON......Page 24
CHARACTERISTICS OF NEUROGLIA......Page 31
REFERENCES......Page 38
PHOSPHOLIPID BILAYERS......Page 40
MEMBRANE PROTEINS......Page 43
BIOLOGICAL MEMBRANES......Page 44
REFERENCES......Page 50
PROPERTIES OF BRAIN LIPIDS......Page 52
COMPLEX LIPIDS......Page 53
ANALYSIS OF BRAIN LIPIDS......Page 57
BRAIN LIPID BIOSYNTHESIS......Page 58
GENES FOR LIPID-SYNTHESIZING ENZYMES......Page 63
LIPIDS IN THE CELLULAR MILIEU......Page 65
REFERENCES......Page 68
GENERAL REFERENCES......Page 67
THE MYELIN SHEATH......Page 69
CHARACTERISTIC COMPOSITION OF MYELIN......Page 74
DEVELOPMENTAL AND METABOLIC ASPECTS OF MYELIN......Page 85
REFERENCES......Page 88
INTRODUCTION......Page 90
PRIMARY ION TRANSPORTERS......Page 91
Ca2+ PUMPS......Page 96
ATP-BINDING CASSETTES......Page 99
SECONDARY ACTIVE TRANSPORT......Page 101
PHYSIOLOGICAL ASPECTS OF THE NEUROTRANSMITTER TRANSPORTERS......Page 103
CATION ANTIPORTERS......Page 104
FACILITATORS......Page 106
REFERENCES......Page 108
MEMBRANE POTENTIALS AND ELECTRICAL SIGNALS IN EXCITABLE CELLS......Page 112
ACTION POTENTIALS IN ELECTRICALLY EXCITABLE CELLS......Page 115
FUNCTIONAL PROPERTIES OF VOLTAGE- GATED ION CHANNELS......Page 116
THE VOLTAGE-GATED ION CHANNEL SUPERFAMILY......Page 118
THE MOLECULAR BASIS FOR ION CHANNEL FUNCTION......Page 120
ION CHANNEL DIVERSITY......Page 124
REFERENCES......Page 125
OVERVIEW......Page 127
THE IMMUNOGLOBULIN GENE SUPERFAMILY......Page 128
THE CADHERIN FAMILY......Page 130
CELL ADHESION MOLECULES AND AXONAL OUTGROWTH......Page 132
CELL ADHESION MOLECULES IN MYELINATION......Page 134
SUMMARY......Page 135
REFERENCES......Page 136
The Cytoskeleton of Neurons and Glia......Page 138
MOLECULAR COMPONENTS OF THE NEURONAL CYTOSKELETON......Page 139
ULTRASTRUCTURE AND MOLECULAR ORGANIZATION OF NEURONS AND GLIA......Page 146
CYTOSKELETAL STRUCTURES IN THE NEURON HAVE COMPLEMENTARY DISTRIBUTIONS AND FUNCTIONS......Page 147
REFERENCES......Page 150
GENERAL MECHANISMS OF INTRACELLULAR MEMBRANE TRAFFICKING IN MAMMALIAN CELLS INCLUDE BOTH UNIVERSAL AND HIGHLY SPECIALIZED PROCESSES......Page 153
FUNDAMENTALS OF MEMBRANE TRAFFICKING ARE BASED ON A SET OF COMMON PRINCIPLES......Page 155
THE BIOSYNTHETIC SECRETORY PATHWAY INCLUDES SYNTHETIC, PROCESSING, TARGETING AND SECRETORY STEPS......Page 158
THE ENDOCYTIC PATHWAY PLAYS MULTIPLE ROLES IN CELLS OF THE NERVOUS SYSTEM......Page 165
SYNAPTIC VESICLE TRAFFICKING IS A SPECIALIZED FORM OF REGULATED SECRETION AND RECYCLING OPTIMIZED FOR SPEED AND EFFICIENCY......Page 172
REFERENCES......Page 176
Intercellular Signaling......Page 178
SYNAPTIC TRANSMISSION......Page 180
CELLULAR SIGNALING MECHANISMS......Page 190
REFERENCES......Page 195
Acetylcholine......Page 197
ORGANIZATION OF THE CHOLINERGIC NERVOUS SYSTEM......Page 198
FUNCTIONAL ASPECTS OF CHOLINERGIC NEUROTRANSMISSION......Page 201
SYNTHESIS, STORAGE AND RELEASE OF ACETYLCHOLINE......Page 204
ACETYLCHOLINESTERASE AND THE TERMINATION OF ACETYLCHOLINE ACTION......Page 207
NICOTINIC RECEPTORS......Page 209
MUSCARINIC RECEPTORS......Page 215
REFERENCES......Page 220
BIOSYNTHESIS OF CATECHOLAMINES......Page 222
STORAGE AND RELEASE OF CATECHOLAMINES......Page 224
CATECHOLAMINE RECEPTORS......Page 228
DOPAMINE RECEPTORS......Page 229
ADRENERGIC RECEPTORS......Page 231
DYNAMICS OF CATECHOLAMINE RECEPTORS......Page 232
REFERENCES......Page 234
SEROTONIN, THE NEUROTRANSMITTER......Page 237
SEROTONIN RECEPTORS......Page 250
REFERENCES......Page 257
HISTAMINE: THE MESSENGER AND THE MOLECULE......Page 259
HISTAMINERGIC CELLS OF THE CENTRAL NERVOUS SYSTEM: ANATOMY AND MORPHOLOGY......Page 260
DYNAMICS OF HISTAMINE IN THE BRAIN......Page 263
MOLECULAR SITES OF HISTAMINE ACTION......Page 266
HISTAMINE ACTIONS ON THE NERVOUS SYSTEM......Page 271
SIGNIFICANCE OF BRAIN HISTAMINE FOR DRUG ACTION......Page 272
REFERENCES......Page 273
Glutamate......Page 276
THE AMINO ACID GLUTAMATE IS THE MAJOR EXCITATORY NEUROTRANSMITTER IN THE BRAIN......Page 277
GLUTAMINE IS AN IMPORTANT IMMEDIATE PRECURSOR FOR GLUTAMATE: THE GLUTAMINE CYCLE......Page 278
SYNAPTIC VESICLES ACCUMULATE TRANSMITTER GLUTAMATE BY VESICULAR GLUTAMATE TRANSPORTERS......Page 279
LONG-TERM POTENTIATION OR DEPRESSION OF GLUTAMATERGIC SYNAPSES MAY UNDERLIE LEARNING......Page 280
THE NEURONAL PATHWAYS OF THE HIPPOCAMPUS ARE ESSENTIAL STRUCTURES FOR MEMORY FORMATION......Page 281
THREE CLASSES OF IONOTROPIC GLUTAMATE RECEPTORS ARE IDENTIFIED......Page 282
GLUTAMATE PRODUCES EXCITATORY POSTSYNAPTIC POTENTIALS......Page 290
METABOTROPIC GLUTAMATE RECEPTORS MODULATE SYNAPTIC TRANSMISSION......Page 291
PROTEINS OF THE POSTSYNAPTIC DENSITY MEDIATE INTRACELLULAR EFFECTS OF GLUTAMATE RECEPTOR ACTIVATION......Page 293
SMALL GTP-BINDING PROTEINS ( GTPases) MEDIATE CHANGES IN GENE EXPRESSION UPON NMDA RECEPTOR ACTIVATION......Page 294
SODIUM-DEPENDENT SYMPORTERS IN THE PLASMA MEMBRANES CLEAR GLUTAMATE FROM THE EXTRACELLULAR SPACE......Page 295
EXCESSIVE GLUTAMATE RECEPTOR ACTIVATION MAY MEDIATE CERTAIN NEUROLOGICAL DISORDERS......Page 296
REFERENCES......Page 298
GABA SYNTHESIS, UPTAKE AND RELEASE......Page 300
STRUCTURE AND FUNCTION OF GABA RECEPTORS......Page 302
GLYCINE RECEPTOR PHYSIOLOGY AND PHARMACOLOGY......Page 307
GLYCINE RECEPTORS: STRUCTURE, PATHOLOGY AND LOCALIZATION......Page 308
REFERENCES......Page 309
PURINE RELEASE AND METABOLISM......Page 311
PURINERGIC RECEPTORS......Page 314
EFFECTS OF PURINES IN THE NERVOUS SYSTEM: ADENOSINE RECEPTORS......Page 320
EFFECTS OF PURINES IN THE NERVOUS SYSTEM: ATP RECEPTORS......Page 322
REFERENCES......Page 323
NEUROPEPTIDES......Page 325
NEUROPEPTIDE RECEPTORS......Page 334
NEUROPEPTIDE FUNCTIONS AND REGULATION......Page 336
PEPTIDERGIC SYSTEMS IN DISEASE......Page 338
REFERENCES......Page 339
Intracellular Signaling......Page 341
HETEROTRIMERIC G PROTEINS......Page 342
SMALL G PROTEINS......Page 349
OTHER FEATURES OF G PROTEINS......Page 350
REFERENCES......Page 351
THE INOSITOL LIPIDS......Page 353
THE INOSITOL PHOSPHATES......Page 360
DIACYLGLYCEROL......Page 362
PHOSPHOINOSITIDES AND CELL REGULATION......Page 364
ACKNOWLEDGMENTS......Page 365
REFERENCES......Page 366
INTRODUCTION: THE SECOND MESSENGER HYPOTHESIS......Page 367
ADENYLYL CYCLASES......Page 368
GUANYLYL CYCLASE......Page 374
PHOSPHODIESTERASES......Page 376
FUNCTIONAL ROLES FOR CYCLIC cAMP AND CYCLIC cGMP......Page 381
REFERENCES......Page 382
MEASUREMENT OF CELLULAR Ca2+ CONCENTRATIONS AND MOVEMENTS......Page 384
Ca2+ REGULATION AT THE PLASMA MEMBRANE......Page 385
Ca2+ STORES AND Ca2+ POOLS......Page 386
Ca2+ SIGNALING......Page 387
Ca2+-REGULATED PROCESSES......Page 393
REFERENCES......Page 394
PROTEIN PHOSPHORYLATION IS OF FUNDAMENTAL IMPORTANCE IN BIOLOGICAL REGULATION......Page 396
PROTEIN SERINE–THREONINE KINASES......Page 399
PROTEIN SERINE–THREONINE PHOSPHATASES......Page 404
NEURONAL PHOSPHOPROTEINS......Page 406
PROTEIN PHOSPHORYLATION MECHANISMS IN DISEASE......Page 415
REFERENCES......Page 416
TYROSINE PHOSPHORYLATION IN THE NERVOUS SYSTEM......Page 419
PROTEIN TYROSINE KINASES......Page 420
PROTEIN TYROSINE PHOSPHATASES......Page 427
ROLE OF TYROSINE PHOSPHORYLATION IN THE NERVOUS SYSTEM......Page 430
REFERENCES......Page 436
Growth, Development and Differentiation......Page 438
FUNDAMENTAL CONCEPTS UNIFYING DEVELOPMENTAL DIVERSITY......Page 439
GENERAL DEVELOPMENT OF THE NERVOUS SYSTEM......Page 440
DEVELOPMENTAL PROCESSES: ENVIRONMENTAL FORCES MOLDING GENETIC POTENTIAL......Page 442
MOLECULAR MECHANISMS OF DEVELOPMENT......Page 444
CELL LINEAGES OF THE NERVOUS SYSTEM......Page 451
REFERENCES......Page 459
THE TRANSCRIPTIONAL PROCESS......Page 461
REGULATION OF TRANSCRIPTION BY TRANSCRIPTION FACTORS......Page 463
GLUCOCORTICOID AND MINERALOCORTICOID RECEPTORS AS TRANSCRIPTION FACTORS......Page 465
CYCLIC AMP REGULATION OF TRANSCRIPTION......Page 468
REFERENCES......Page 471
GROWTH FACTORS ARE ESSENTIAL FOR NERVOUS SYSTEM DEVELOPMENT AND FUNCTION......Page 473
CLASSES OF GROWTH FACTORS ACTING IN THE NERVOUS SYSTEM......Page 475
REFERENCES......Page 485
NEURONAL ORGANELLES IN MOTION......Page 487
DISCOVERY AND CONCEPTUAL DEVELOPMENT OF FAST AND SLOW AXONAL TRANSPORT......Page 488
FAST AXONAL TRANSPORT......Page 490
SLOW AXONAL TRANSPORT......Page 495
MOLECULAR MOTORS: KINESIN, DYNEIN AND MYOSIN......Page 497
REFERENCES......Page 501
STEM CELLS ARE MULTIPOTENT AND SELF- RENEWING......Page 504
STEM CELLS CONTRIBUTE TO THE DEVELOPING NERVOUS SYSTEM......Page 508
NEUROGENESIS OCCURS IN THE ADULT BRAIN......Page 510
STEM CELLS OFFER THE POTENTIAL FOR REPAIR IN THE ADULT NERVOUS SYSTEM......Page 511
STEM CELL TRANSPLANTS FOR NEURAL REPAIR......Page 513
EXPANDING ENDOGENOUS NEURAL STEM CELLS FOR REPAIR......Page 514
CONCLUSIONS......Page 515
REFERENCES......Page 516
Axonal Growth in the Adult Mammalian Nervous System: Regeneration and Compensatory Plasticity......Page 518
REGENERATION IN THE PERIPHERAL NERVOUS SYSTEM......Page 519
REGENERATION IN THE CENTRAL NERVOUS SYSTEM......Page 521
CENTRAL NERVOUS SYSTEM INJURY AND COMPENSATORY PLASTICITY......Page 525
REFERENCES......Page 527
Metabolism......Page 529
Energy Metabolism of the Brain......Page 530
INTRODUCTION......Page 531
SUBSTRATES FOR CEREBRAL ENERGY METABOLISM......Page 532
AGE AND DEVELOPMENT INFLUENCE CEREBRAL ENERGY METABOLISM......Page 534
REGULATION OF THE CEREBRAL METABOLIC RATE......Page 535
METABOLISM IN THE BRAIN IS HIGHLY COMPARTMENTALIZED......Page 536
GLYCOLYSIS: CONVERSION OF GLUCOSE TO PYRUVATE OR LACTATE......Page 537
THE PENTOSE PHOSPHATE SHUNT IS ACTIVE IN BRAIN......Page 539
THE MALATE–ASPARTATE SHUTTLE HAS A KEY ROLE IN BRAIN METABOLISM......Page 540
THERE IS DYNAMIC METABOLISM OF LACTATE IN BRAIN......Page 541
THE COMPLETE OXIDATION OF GLUCOSE REQUIRES TRICARBOXYLIC ACID CYCLE ACTIVITY......Page 542
ENERGY OUTPUT AND OXYGEN CONSUMPTION ARE ASSOCIATED WITH TCA CYCLE ACTIVITY......Page 543
MANY TCA CYCLE ENZYMES AND COMPONENTS OF OXIDATIVE PHOSPHORYLATION ARE DIFFERENTIALLY DISTRIBUTED IN NEURONAL AND GLIAL MITOCHONDRIA......Page 544
GLUTAMATE/GLUTAMINE METABOLISM IS LINKED TO ENERGY METABOLISM......Page 546
HOW COMPARTMENTALIZED BRAIN METABOLISM IS STUDIED......Page 548
REFERENCES......Page 551
HYPOXIA–ISCHEMIA AND BRAIN INFARCTION......Page 557
MICROVASCULAR INJURY IN HYPOXIA – ISCHEMIA......Page 560
EXCITOTOXIC INJURY IN HYPOXIA – ISCHEMIA......Page 561
ISCHEMIC APOPTOSIS......Page 563
FREE RADICALS IN HYPOXIA– ISCHEMIA......Page 564
REFERENCES......Page 569
Eicosanoids, Docosanoids, Platelet- Activating Factor and Infl ammation......Page 572
STORAGE OF LIPID MESSENGERS IN NEURAL MEMBRANE PHOSPHOLIPIDS......Page 573
PHOSPHOLIPASE A2......Page 574
PLATELET-ACTIVATING FACTOR......Page 576
CYCLOOXYGENASES......Page 578
LIPID SIGNALING PATHWAYS AND NEUROINFLAMMATION......Page 581
DOCOSAHEXAENOIC ACID......Page 583
THE FUTURE OF LIPID SIGNALING IN THE NERVOUS SYSTEM......Page 584
REFERENCES......Page 585
Metabolic Encephalopathies......Page 590
METABOLIC ENCEPHALOPATHY DUE TO LACK OF ENERGY SUBSTRATE......Page 589
HYPONATREMIC ENCEPHALOPATHY......Page 591
METABOLIC ENCEPHALOPATHY DUE TO PERIPHERAL ORGAN FAILURE......Page 592
THIAMINE DEFICIENCY (WERNICKE’S) ENCEPHALOPATHY......Page 595
REFERENCES......Page 598
DISTINGUISHING FEATURES OF APOPTOSIS AND NECROSIS......Page 599
APOPTOSIS......Page 600
NECROSIS......Page 609
TARGETING APOPTOSIS AND NECROSIS IN NEUROLOGICAL DISORDERS......Page 610
REFERENCES......Page 611
Inherited and Neurodegenerative Diseases......Page 612
Peripheral Neuropathy......Page 613
FEATURES OF PERIPHERAL NERVES THAT INFLUENCE THEIR VULNERABILITY TO DISEASE AND CAPACITY FOR REGENERATION......Page 614
PATHOGENESIS OF NEUROPATHIES......Page 615
REFERENCES......Page 620
EPILEPSY IS A COMMON NEUROLOGICAL DISORDER......Page 623
MECHANISMS OF ANTISEIZURE DRUGS......Page 628
GENETICS OF EPILEPSY......Page 629
REFERENCES......Page 632
GENERAL CLASSIFICATION......Page 633
ACQUIRED ALLERGIC AND/OR INFECTIOUS DISEASES OF MYELIN......Page 634
GENETICALLY DETERMINED DISORDERS OF MYELIN......Page 641
TOXIC AND NUTRITIONAL DISORDERS OF MYELIN DISORDERS PRIMARILY AFFECTING NEURONS WITH SECONDARY INVOLVEMENT OF MYELIN......Page 643
REPAIR IN DEMYELINATING DISEASES......Page 644
REFERENCES......Page 645
GENETIC ASPECTS OF COMMON NEURODEGENERATIVE DISEASES......Page 647
ALZHEIMER’S DISEASE......Page 649
PARKINSON’S DISEASE......Page 651
FRONTOTEMPORAL DEMENTIA......Page 653
NEURODEGENERATIVE TRIPLET REPEAT DISORDERS......Page 655
CREUTZFELDT–JAKOB DISEASE AND OTHER PRION DISEASES......Page 656
REFERENCES......Page 657
Disorders of Amino Acid Metabolism......Page 661
INTRODUCTION......Page 662
DISORDERS OF BRANCHED-CHAIN AMINO ACIDS: MAPLE SYRUP URINE DISEASE......Page 665
DISORDERS OF PHENYLALANINE METABOLISM: PHENYLKETONURIA......Page 666
DISORDERS OF GLYCINE METABOLISM: NONKETOTIC HYPERGLYCINEMIA......Page 667
DISORDERS OF SULFUR AMINO ACID METABOLISM: HOMOCYSTINURIA......Page 668
THE UREA CYCLE DEFECTS......Page 672
ACID METABOLISM......Page 675
REFERENCES......Page 676
LYSOSOMAL DISEASES......Page 678
PEROXISOMAL DISORDERS......Page 682
PATHOGENESIS OF LYSOSOMAL AND PEROXISOMAL DISORDERS......Page 685
REFERENCES......Page 686
Diseases of Carbohydrate, Fatty Acid and Mitochondrial Metabolism......Page 688
DISEASES OF CARBOHYDRATE AND FATTY ACID METABOLISM IN MUSCLE......Page 689
DISEASES OF CARBOHYDRATE AND FATTY ACID METABOLISM IN BRAIN......Page 696
DISEASES OF MITOCHONDRIAL METABOLISM......Page 699
REFERENCES......Page 704
ORGANIZATION OF THE NEUROMUSCULAR JUNCTION......Page 706
EXCITATION AND CONTRACTION OF THE MUSCLE FIBER......Page 709
GENETIC DISORDERS OF THE NEUROMUSCULAR JUNCTION......Page 712
HEREDITARY DISEASES OF MUSCLE MEMBRANES......Page 713
IMMUNE DISEASES OF MUSCLE EXCITABILITY......Page 716
TOXINS AND METABOLITES THAT ALTER MUSCULAR EXCITATION......Page 718
REFERENCES......Page 722
AMYOTROPHIC LATERAL SCLEROSIS IS THE MOST COMMON ADULT ONSET MOTOR NEURON DISEASE......Page 724
NON-TRANSGENIC, INDUCED MODELS OF MOTOR NEURON DISEASE......Page 727
SELECTED GENETIC MODELS OF RELEVANCE TO AMYOTROPHIC LATERAL SCLEROSIS......Page 728
REFERENCES......Page 732
Neurodegenerative Synucleinopathies and Tauopathies......Page 737
THE SYNUCLEIN FAMILY......Page 738
PARKINSON’S DISEASE AND OTHER LEWY BODY DISEASES......Page 739
MULTIPLE SYSTEM ATROPHY......Page 741
SYNUCLEINOPATHIES......Page 742
TAU ISOFORMS AND THEIR INTERACTIONS WITH MICROTUBULES......Page 743
TAU AND ALZHEIMER’S DISEASE......Page 744
SPORADIC TAUOPATHIES......Page 745
MUTATIONS CAUSING TAUOPATHY— THE FTDP- 17 SYNDROMES......Page 746
SYNTHETIC TAU FILAMENTS......Page 747
ANIMAL MODELS OF HUMAN TAUOPATHIES......Page 748
TAUOPATHIES — OUTLOOK......Page 749
REFERENCES......Page 750
ANATOMY AND PHYSIOLOGY OF THE BASAL GANGLIA......Page 752
DISORDERS THAT INVOLVE BASAL GANGLIA DYSFUNCTION......Page 757
REFERENCES......Page 768
ALZHEIMER’S DISEASE IS THE MOST PREVALENT NEURODEGENERATIVE DISORDER......Page 771
REFERENCES......Page 777
INTRODUCTION......Page 781
ANIMAL PRION DISEASES......Page 782
HUMAN PRION DISEASES......Page 783
PRION DISEASE PATHOLOGY AND PATHOGENESIS......Page 784
THE PROTEIN-ONLY HYPOTHESIS OF PRION PROPAGATION......Page 785
CHARACTERIZATION OF PrPC......Page 786
CHARACTERIZATION OF PrPSC......Page 787
THE MOLECULAR BASIS OF PRION STRAIN DIVERSITY......Page 789
PRION TRANSMISSION BARRIERS......Page 790
CELL DEATH IN PRION DISEASE......Page 791
REFERENCES......Page 792
Sensory Transduction......Page 794
PHYSIOLOGICAL BACKGROUND......Page 795
PHOTORECEPTOR MEMBRANES AND VISUAL PIGMENTS......Page 797
PHOTOTRANSDUCTION......Page 800
COLOR BLINDNESS RETINITIS PIGMENTOSA......Page 802
REFERENCES......Page 803
OLFACTION......Page 805
TASTE......Page 813
REFERENCES......Page 817
GENERAL FEATURES OF MECHANORECEPTORS......Page 820
MODEL SYSTEMS......Page 821
HAIR CELLS......Page 822
DEAFNESS......Page 826
REFERENCES......Page 827
Neural Processing and Behavior......Page 828
INTRODUCTION......Page 829
BEHAVIORAL CONTROL OF HORMONAL SECRETION......Page 830
CLASSIFICATION OF HORMONAL EFFECTS......Page 832
BIOCHEMISTRY OF STEROID AND THYROID HORMONE ACTIONS......Page 833
INTRACELLULAR STEROID RECEPTORS: PROPERTIES AND TOPOGRAPHY......Page 837
MEMBRANE STEROID RECEPTORS AND SIGNALING PATHWAYS......Page 838
BIOCHEMISTRY OF THYROID HORMONE ACTIONS ON BRAIN......Page 839
DIVERSITY OF STEROID-HORMONE ACTIONS ON THE BRAIN......Page 840
REFERENCES......Page 843
BRIEF HISTORY OF MEMORY RESEARCH IN HUMANS......Page 845
MOLECULAR MECHANISMS OF LEARNING......Page 847
MOLECULAR MECHANISMS OF MEMORY CONSOLIDATION AND STORAGE......Page 853
FUTURE DIRECTIONS AND CHALLENGES......Page 858
REFERENCES......Page 859
CLINICAL ASPECTS OF SCHIZOPHRENIA......Page 861
BRAIN IMAGING......Page 864
CELLULAR AND MOLECULAR STUDIES......Page 866
REFERENCES......Page 870
Neurobiology of Severe Mood and Anxiety Disorders......Page 872
MOOD DISORDERS......Page 873
NEUROTRANSMITTER AND NEUROPEPTIDE SYSTEMS ARE IMPLICATED IN THE PATHOPHYSIOLOGY OF BIPOLAR AND MAJOR DEPRESSIVE DISORDERS......Page 874
NEUROANATOMICAL AND NEUROPATHOLOGICAL CORRELATES OF MOOD DISORDERS......Page 879
INTRACELLULAR SIGNALING PATHWAYS INTEGRATE ENVIRONMENTAL AND GENETIC CUES INVOLVED IN MOOD......Page 880
ANXIETY DISORDERS......Page 884
INTRACELLULAR TARGETS FOR ANXIETY DISORDERS......Page 889
REFERENCES......Page 890
GENERAL PRINCIPLES......Page 895
NEURONAL CIRCUITRY OF ADDICTION......Page 896
OPIATES......Page 898
PSYCHOMOTOR STIMULANTS......Page 900
CANNABINOIDS (MARIJUANA)......Page 903
NICOTINE......Page 905
ETHANOL, SEDATIVES AND ANXIOLYTICS......Page 906
ADDICTION AND NEURONAL PLASTICITY SHARE COMMON CELLULAR MECHANISMS......Page 907
ACKNOWLEDGMENTS......Page 908
REFERENCES......Page 909
INTRODUCTION: THE PAIN PATHWAY......Page 911
PRIMARY SENSORY NEURONS......Page 912
DORSAL HORN......Page 914
THE BRAIN......Page 915
CLINICAL PAIN......Page 916
INFLAMMATORY PAIN......Page 917
NEUROPATHIC PAIN......Page 919
REFERENCES......Page 921
Neuroimaging......Page 922
MAGNETIC RESONANCE IMAGING ( MRI)......Page 923
MAGNETIC RESONANCE SPECTROSCOPY ( MRS)......Page 925
POSITRON EMISSION TOMOGRAPHY ( PET) AND SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY ( SPECT)......Page 927
APPLICATIONS OF PET AND SPECT FOR BRAIN FUNCTION......Page 928
CNS DRUG DESIGN AND PRECLINICAL/ CLINICAL DRUG DEVELOPMENT......Page 931
CLINICAL APPLICATIONS OF PET AND SPECT......Page 932
APPENDIX......Page 933
REFERENCES......Page 940
Glossary......Page 945
Index......Page 951