From molecules to networks j byrne (elsevier, 2004)

Byrne_FM(i-xiv).qxd 9/5/03 12:47 PM Page xi Contributors Numbers in parentheses indicate the pages on which the authors’ contributions begin Douglas A Baxter (161, 391) Department of Neurobiology and Anatomy, The University of Texas-Houston, Medical School Houston, TX, USA Scott T Brady (31) Department of Anatomy and Cell Biology, University of Illinois at Chicago, Il, USA Peter J Brophy (31) Department of Preclinical Veterinary Sciences, University of Edinburgh, Edinburgh, Scotland, UK Thomas H Brown (499) Department of Psychology, Yale University, New Haven, CT, USA John H Byrne (161, 391, 459, 499) Department of Neurobiology and Anatomy, University of Texas Health Science Center, Houston, TX, USA Carmen C Canavier (161) Department of Psychology, University of New Orleans, New Orleans, LA, USA Luz Claudio (1) Department of Community and Preventive Medicine, Mt Sinai School of Medicine, New York, NY, USA David R Colman (1, 31) Montreal Neurological Institute, McGill University, Montreal, QC, CANADA Jean De Vellis (1) Department of Neurobiology, University of California Los Angeles, School of Medicine, Los Angeles, CA, USA Rolf Dermietzel (431) Institut für Anatomie, Ruhr Universität Bochum, Germany Ariel Y Deutch (245, 279) Department of Psychiatry and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA Patrick R Hof (1) Neurobiology of Aging Laboratories, Mt Sinai School of Medicine, New York, NY, YSA Yuh Nung Jan (141) Department of Physiology, University of California, San Francisco, CA USA Lily Yeh Jan (141) Department of Physiology, University of California, San Francisco, CA USA Dimitri M Kullmann (197) Institute of Neurology, University College London, London, UK Kevin S LaBar (499) Center for Cognitive Neuroscience, Duke University, Durham, NC, USA Joseph E LeDoux (499) Center for Neural Science, New York University, New York, NY, USA Derick H Lindquist (499) Department of Psychology, Yale University, New Haven, CT, USA James R Lundblad (371) Division of Molecular Medicine, Oregon Health Sciences University, Portland, OR, USA Pierre J Magistretti (67) Institute de Physiologie, Université of Lausanne, Lausanne, Switzerland David A McCormick (115) Section of Neurobiology, Yale University School of Medicine, New Haven, CT, USA James L Roberts (279, 371) Department of Pharmacology, University of Texas San Antonio, San Antonio, TX, USA Robert H Roth (245) Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA Renato Rozental (431) Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA Eliana Scemes (431) Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA Howard Schulman (335) View, CA, USA SurroMed, Inc., Mountain Byrne_FM(i-xiv).qxd xii 9/5/03 12:47 PM Page xii CONTRIBUTORS Thomas L Schwarz (197) Department of Neurology, Children’s Hospital, Boston, MA, USA Gordon M Shepherd (91, 479) Section of Neurobiology, Yale University School of Medicine, New Haven, CT, USA Paul D Smolen (391) Department of Neurobiology and Anatomy, University of Texas Health Science Center, Houston, TX, USA David C Spray (431) Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA Timothy J Teyler (499) Medical Education Program, University of Idaho, Moscow, ID, USA Richard F Thompson (499) Department of Psychology, The University of Southern California, Los Angeles, CA, USA Bruce D Trapp (1) Department of Neuroscience, Cleveland Clinic Foundation, Cleveland, OH, USA M Neal Waxham (299) Department of Neurobiology and Anatomy, University of Texas Health Science Center, Houston, TX, USA Robert S Zucker (197) Neurobiology Division, Molecular and Cell Biology Department, University of California, Berkeley, CA, USA Byrne_FM(i-xiv).qxd 9/5/03 12:47 PM Page xiii Preface The past twenty years have witnessed an exponential increase in the understanding of the nervous system at all levels of analyses Perhaps the most striking developments have been in the understanding of the cell and molecular biology of the neuron The field has moved from treating the neuron as a simple black box that added up impinging synaptic input to fire an action potential to one in which the function of nerve cells involves a host of biochemical and biophysical processes that act synergistically to process, transmit and store information In this book, we have attempted to provide a comprehensive summary of current knowledge of the morphological, biochemical, and biophysical properties of nerve cells The book is intended for graduate students, advanced undergraduate students, and professionals The chapters are highly referenced so that readers can pursue topics of interest in greater detail We have also included material on mathematical modeling approaches to analyze the complex synergistic processes underlying the operation and regulation of nerve cells These modeling approaches are becoming increasingly important to facilitate the understanding of membrane excitability, synaptic transmission, as well gene and protein networks The final chapter in the book illustrates the ways in which the great strides in understanding the biochemical and biophysical properties of nerve cells have led to fundamental insights into an important aspect of cognition, memory We are extremely grateful to the many authors who have contributed to the book, and the support and encouragement during the two past years of Jasna Markovac and Johannes Menzel of Academic Press We would also like to thank Evangelos Antzoulatos, Evyatar Av-Ron, Diasinou Fioravanti, Yoshihisa Kubota, Rong-Yu Liu, Fred Lorenzetii, Riccardo Mozzachiodi, Gregg Phares, Travis Rodkey, and Fredy Reyes for help with editing the chapters John H Byrne James L Roberts Byrne_cha01(1-30).qxd 8/29/03 11:24 AM Page C H A P T E R Cellular Components of Nervous Tissue Patrick R Hof, Bruce D Trapp, Jean de Vellis, Luz Claudio, and David R Colman contacts with other cells are made, displays a wide range of morphological specializations, depending on its target area in the central or peripheral nervous system Classically, two major morphological types of contacts, or synapses, may be recognized by electron microscopy: the asymmetric synapses, responsible for transmission of excitatory inputs, and the symmetric or inhibitory synapses The cell body and the dendrites are the two major domains of the cell that receive inputs, and the dendrites play a critically important role in providing a massive receptive area on the neuronal surface In addition, there is a characteristic shape for each dendritic arbor, which is used to classify neurons into morphological types Both the structure of the den- Several types of cellular elements are integrated to yield normally functioning brain tissue The neuron is the communicating cell, and a wide variety of neuronal subtypes are connected to one another via complex circuitries usually involving multiple synaptic connections Neuronal physiology is supported and maintained by the neuroglial cells, which have highly diverse and incompletely understood functions These include myelination, secretion of trophic factors, maintenance of the extracellular milieu, and scavenging of molecular and cellular debris from it Neuroglial cells also participate in the formation and maintenance of the blood–brain barrier, a multicomponent structure that is interposed between the circulatory system and the brain substance and that serves as the molecular gateway to the brain parenchyma THE NEURON Dendritic branches with spines Neurons are highly polarized cells, meaning that they develop, in the course of maturation, distinct subcellular domains that subserve different functions Morphologically, in a typical neuron, three major regions can be defined: (1) the cell body, or perikaryon, which contains the nucleus and the major cytoplasmic organelles; (2) a variable number of dendrites, which emanate from the perikaryon and ramify over a certain volume of gray matter and which differ in size and shape, depending on the neuronal type; and (3) a single axon, which extends in most cases much farther from the cell body than does the dendritic arbor (Fig 1.1) The dendrites may be spiny (as in pyramidal cells) or nonspiny (as in most interneurons), whereas the axon is generally smooth and emits a variable number of branches (collaterals) In vertebrates, many axons are surrounded by an insulating myelin sheath, which facilitates rapid impulse conduction The axon terminal region, where From Molecules to Networks Apical dendrite Axon Purkinje cell of cerebellar cortex Axon Pyramidal cell of cerebral cortex FIGURE 1.1 Typical morphology of projection neurons On the left is a Purkinje cell of the cerebellar cortex, and on the right, a pyramidal neuron of the neocortex These neurons are highly polarized Each has an extensively branched, spiny apical dendrite, shorter basal dendrites, and a single axon emerging from the basal pole of the cell Copyright 2004, Elsevier Science (USA) All rights reserved Byrne_cha01(1-30).qxd 8/29/03 11:24 AM Page 2 CELLULAR COMPONENTS OF NERVOUS TISSUE dritic arbor and the distribution of axonal terminal ramifications confer a high level of subcellular specificity in the localization of particular synaptic contacts on a given neuron The three-dimensional distribution of the dendritic arborization is also important with respect to the type of information transferred to the neuron A neuron with a dendritic tree restricted to a particular cortical layer may receive a very limited pool of afferents, whereas the widely expanded dendritic arborizations of a large pyramidal neuron will receive highly diversified inputs within the different cortical layers in which segments of the dendritic tree are present (Fig 1.2) (Mountcastle, 1978; Peters and Jones, 1984; Schmitt et al., 1981; Szentagothai and Arbib, 1974; Lund et al., 1995; Björklund et al., 1990) The structure of the dendritic tree is maintained by surface interactions between adhesion molecules and, intracellularly, by an array of cytoskeletal elements (microtubules, neurofilaments, and associated proteins), which also take part in the movement of organelles within the dendritic cytoplasm An important specialization of the dendritic arbor of certain neurons is the presence of large numbers of dendritic spines, which are membrane-limited organelles that project from the surface of the den- III Corticocortical afferents IV Axon Spiny stellate cell from layer IV Recurrent collateral from pyramidal cell in layer V Thalamocortical afferents FIGURE 1.2 Schematic representation of four major excitatory inputs to pyramidal neurons A pyramidal neuron in layer III is shown as an example Note the preferential distribution of synaptic contacts on spines Spines are labeled in red Arrow shows a contact directly on the dendritic shaft drites They are abundant in large pyramidal neurons and are much sparser on the dendrites of interneurons Spines are more numerous on the apical shafts of the pyramidal neurons than on the basal dendrites As many as 30,000 to 40,000 spines are present on the largest pyramidal neurons Spines constitute the region of the dendritic arborization that receives most of the excitatory input Each spine generally contains one asymmetric synapse; thus, the approximate density of excitatory input on a neuron can be inferred from an estimate of its number of spines The cytoplasm within the spines is characterized by the presence of polyribosomes and a variety of filaments, including actin and ␣- and ␤-tubulin, as well as a spine apparatus comprising cisternae, membrane vesicles, and stacks of dense lamellar material (see Box 1.1) (see (Berkley, 1896; Gray, 1959; Ramón y Cajal, 1955; Coss and Perkel, 1985; Scheibel and Scheibel, 1968; Steward and Falk, 1986; Zhang and Benson, 2000; Nimchinsky et al., 2002) The perikaryon contains the nucleus and a variety of cytoplasmic organelles Stacks of rough endoplasmic reticulum are conspicuous in large neurons and, when interposed with arrays of free polyribosomes, are referred to as Nissl substance Another feature of the perikaryal cytoplasm is the presence of a rich cytoskeleton composed primarily of neurofilaments and microtubules, discussed in detail in Chapter These cytoskeletal elements are dispersed in “bundles” that extend into the axon and dendrites (Peters and Jones, 1984) Whereas the dendrites and the cell body can be characterized as the domains of the neuron that receive afferents, the axon, at the other pole of the neuron, is responsible for transmitting neural information This information may be primary, in the case of a sensory receptor, or processed information that has already been modified through a series of integrative steps The morphology of the axon and its course through the nervous system are correlated with the type of information processed by the particular neuron and by its connectivity patterns with other neurons The axon leaves the cell body from a small swelling called the axon hillock This structure is particularly apparent in large pyramidal neurons; in other cell types, the axon sometimes emerges from one of the main dendrites At the axon hillock, microtubules are packed into bundles that enter the axon as parallel fascicles The axon hillock is the part of the neuron from which the action potential is generated The axon is generally unmyelinated in local-circuit neurons (such as inhibitory interneurons), but it is myelinated in neurons that furnish connections between different parts of the nervous system Axons usually have larger numbers Byrne_cha18(499-574).qxd 8/29/03 11:53 AM Page 569 SUMMARY Aizawa, and M Katsuki, Eds.), (pp 3–15 Japan Scientific Societies Press, Tokyo Kim, J J., Clark, R E., and Thompson, R F (1995) Hippocampectomy impairs the memory of recently, but not remotely, acquired trace eyeblink conditioned responses Behav 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288–290 Byrne_IDX(575-584).qxd 9/3/03 11:20 AM Page 575 Index A AADC, see L-Aromatic amino acid decarboxylase Acetylcholine (ACh) autoreceptor regulation of storage and release, 271, 273 biosynthesis, 271 history of study, 270–271 inactivation acetylcholinesterase, 273 reuptake with choline transporter, 274 nontransmitter roles, 275–276 receptors, see Muscarinic acetylcholine receptor; Nicotinic acetylcholine receptor vesicular cholinergic transporter, 271 Acetylcholinesterase (AChE) acetylcholine degradation, 273 inhibitor applications, 273 ACh, see Acetylcholine AChE, see Acetylcholinesterase Actin, see Microfilament Action potential activity patterns in central nervous system neurons, 129, 131 ATP consumption in propagation, 76 backpropagation, 156 bursts, 129, 135–136 conductance of sodium and potassium in generation, 121–125 coupling to synaptic vesicle fusion, 219 dendrite effects, see Dendrite initiation studies, 487–488 neuronal ionic current types and functions, 131–132 recording, 122–124, 129 refractory period prevention of reverberation, 125 voltage-clamp studies, 122–124 Action potential propagation ATP consumption, 76 dendrite backpropagation functions conditional axonal output, 489 dendrodendritic inhibition, 488 frequency response, 489 membrane potential resetting, 488 neurotransmitter release, 489 synaptic plasticity, 488–489 From Molecules to Networks synaptic response boosting, 488 overview, 156, 486, 488 myelination effects on speed, 125 Adenylyl cyclase G protein-coupled receptor signaling coincidence detection, 344–345 coupling to receptor, 344 inhibitory control, 344 isoforms and differential regulation, 343–344 Adrenergic receptors classification, 327 pharmacology, 327–328 Afterhyperpolarization, 115, 125 ␥-Aminobutyric acid (GABA) autoreceptor regulation of release, 267–268 biosynthesis, 265, 267 discovery, 265 inactivation enzymatic degradation, 268 reuptake, 268 inhibitory interneurons, 6, receptors, see GABAA; GABAB transporters, 267–268 Amino-3-hydroxy-5methylisoxazoleproprionic acid (AMPA) receptors assembly and subunit diversity, 313–314 long-term depression role, 524–525 long-term potentiation induction, 513–514 RNA splicing and editing of subunits, 314–315 structure, 315 AMPA receptors, see Amino-3-hydroxy-5methylisoxazoleproprionic acid receptors Amygdala, fear conditioning role, 554–556 Aplysia, 531 AP-1, gene expression regulation, 381–382 L-Aromatic amino acid decarboxylase (AADC) catecholamine biosynthesis, 255 serotonin biosynthesis, 262 Aspartate, excitatory neurotransmission, 268 Astrocyte astrocyte–neuron metabolic unit, 87 astrogliosis, 20 575 blood–brain barrier, 18, 27 calcium signaling, 288 calcium waves, 20 development, 18 energy consumption, 77, 79–80 function, 18–22 gap junctions calcium flux, 437, 439 connexin expression, 446 syncytium, 446–448 glutamate metabolism, 84–87 glutamate stimulation of glucose uptake, 80–83 glycogen metabolism, 83–84 hepatic encephalopathy role, 85 ion channels, 19 markers, 18–19 neuropathology brain lesion effects on intercellular coupling, 452 Charcot–Marie–Tooth disease, 450–451 connexin mutation in disease, 434 epilepsy, 448–449 glial tumors, 451–452 protozoan infection effects on intercellular coupling, 453 types, 17–18 ATP, neuron processes in consumption, 76 Augmentation calcium modulation, 236–237 definition, 235 features, 500 Axoaxonic cell, see Chandelier cell Axon basket cells, conduction, 35 definition, 33 dendrite interactions, see Dendrite diameters, 33, 35 differentiation, 33 electrotonic spread, see Cable theory electrotonus, history of study, 92 hillock, 2, 33 initial segment encoding of global neuron output, 484–486 fascicles, 33, 35 microtubules, 50 morphology, 36 Copyright 2004, Elsevier Science (USA) All rights reserved Byrne_IDX(575-584).qxd 9/3/03 11:20 AM 576 Page 576 INDEX Axon (continued) presynaptic terminals, 33 single-axon rule, 480 spiny stellate cells, Axonal transport ATP consumption, 76 fast, 59, 62 regulation, 62–63 slow, 59 B Basket cell axons, markers, BCM rule, see Bienstock–Cooper–Munro rule BDNF, see Brain-derived neurotrophic factor Bienstock–Cooper–Munro (BCM) rule, 526 Bipolar neuron cortical distribution, markers, 8–9 Bistability, 187–189, 402 Blood–brain barrier astrocytes, 27 basement membrane, 26–27 disruption and edema, 27 endothelial cell characteristics, 26 function, 25–26 glucose transporters, 26 pericytes, 27 zonula occludens, 26 Blood supply brain vasculature, 22, 24–25 imaging of blood flow in brain, 71–73 neuronal activity coupling with blood flow, 70–71 Boltzmann equation, 166 Brain-derived neurotrophic factor (BDNF) neurotransmitter functions, 293–294 storage and release, 292–293 synthesis, 291–292 C Cable theory assumptions, 93–96 dynamic changes in neuron electrotonic structure, 106–109 electrotonic length, 98 electrotonic spread dendrites boundary conditions of termination and branching effects, 103–104 synaptic potential modulation by electrotonic spread, 104–105 dependence on characteristic length, 94, 96 dependence on diameter, 96–97 impulse propagation in unmyelinated axons, 100–101 propagation comparison, 102 transient signal dependence on membrane capacitance, 98–100 history of study, 92 myelination effects on conduction speed, 101–102 Calcineurin regulation, 365 structure, 364–365 Calcium/calmodulin-dependent protein kinase II autophosphorylation, 258 cognitive kinase activity, 361–362 consensus target sequence, 357 gene expression regulation, 380 isoforms, 357–358 long-term depression role, 524 long-term potentiation induction, 513–514 modeling, 402, 404 subcellular targeting, 358 substrates, 357 Calcium channels distribution in neurons, 156 ion selectivity, 152–154 long-term potentiation induction by voltage-dependent channels, 515 synaptic vesicle exocytosis role, 206 Calcium currents high-threshold currents in neurons, 134–135 low-threshold currents in neurons, 135–136 signal transduction, 134 types and functions, 131, 134 Calcium flux fluorescent dyes for study, 348, 398 gap junction mediation, 437, 439 long-term depression role, 524 long-term potentiation induction, 510 modeling allosteric interactions and Hill functions, 400–401 buffering considerations, 396–398 discretization of cellular space, 395 electrodiffusion modeling, 396 Euler’s method, 394–395 experimental validation, 398 ordinary differential equations, 394 passive diffusion, 393 positive feedback, 394 symmetry reduction of dimension number, 395–396 signal transduction, 348 subdomains, 348 Calmodulin ion channel modulation, 148 N-methyl-D-aspartate receptor binding, 318 protein–protein interactions, 349 signal transduction, 348–349 Carbon monoxide (CO) mechanism of neuronal effects, 291 neurotransmission, 291 synthesis, 291 Catecholamines autoreceptor regulation of synthesis and release, 257–258 biosynthesis L-aromatic amino acid decarboxylase, 255 dopamine ␤-hydroxylase, 255–256 overview, 250, 253 phenylethanolamine N-methyltransferase, 256 tyrosine hydroxylase, 253–255 functions, 250 inactivation, 258–259 neuronal transporters dopamine, 259, 261 norepinephrine, 259, 261 receptors, see Adrenergic receptors; Dopamine receptors release from vesicles, 257 storage in vesicles, 256 structure, 250 vesicular monoamine transporters, 256–257 Catechol-O-methyltransferase (COMT) catecholamine inactivation, 258–259 inhibitors in neuropsychiatric disorder management, 260 Cerebellum eyeblink conditioning role, 544, 547–553 long-term memory traces, 550–552 memory storage mechanisms, 552–553 Chandelier cell cortical distribution, 7, morphology, Charcot–Marie–Tooth disease (CMT) gap junctions in neuropathology, 450–451 peripheral myelin protein-22 mutations, 17 ChAT, see Choline acetyltransferase Chloride channels inhibitory receptor association, 311–312 structure, 143–144 Choline acetyltransferase (ChAT), acetylcholine synthesis, 271 Chromatin, modification in gene expression regulation, 375–376, 378 Classical conditioning eyeblink conditioning cerebellum role, 544, 547–553 hippocampus role, 544–547 stimuli, 544 fear conditioning amygdala role, 554–556 cellular mechanisms, 557 hippocampus role, 557–558 human fear conditioning and anxiety, 558–560 medial prefrontal cortex role, 557 molecular basis, 557–558 stimuli, 553 Clutch cell cortical distribution, function, CMT, see Charcot–Marie–Tooth disease CO, see Carbon monoxide Byrne_IDX(575-584).qxd 9/3/03 11:20 AM Page 577 577 INDEX Coat protein (COP), roles in protein transport, 40 CLSM, see Confocal laser scanning microscopy Cochlear hair cell, features, 10–11 Compartmental models history of study, 92 signal transduction modeling, 407–408 two-compartment model and signal spread, 99–100 COMT, see Catechol-O-methyltransferase Cone, features, 10–11 Confocal laser scanning microscopy (CLSM), combination with whole-cell recording, 506–508 Connexins, see Gap junction COP, see Coat protein CREB, see Cyclic AMP response elementbinding protein Cyclic AMP-dependent protein kinase, see Protein kinase A Cyclic AMP response element-binding protein (CREB) gene expression regulation, 380–381 long-term sensitization role in Aplysia, 535–536 modeling of gene network regulation, 416–418 Cytoskeleton axonal transport, 59 interaction of cytoskeletal systems, 54–55 intermediate filaments, 52–54 microfilaments, 50–52 microtubules, 48–50 motors, 49, 55–58 protein types, 47 D DAG, see Diacylglycerol DBH, see Dopamine ␤-hydroxylase Dendrite action potential backpropagation functions conditional axonal output, 489 dendrodendritic inhibition, 488 frequency response, 489 membrane potential resetting, 488 neurotransmitter release, 489 synaptic plasticity, 488–489 synaptic response boosting, 488 overview, 156, 486, 488 arborization, 1–2, 35 axonal output control by distal dendrite mechanisms membrane resistance, 483 overview, 482–484 potassium conductance, 483–484 synaptic conductance, 483 voltage-gated depolarizing conductances, 484 axon effects on processing, 480–481 axon initial segment encoding of global output, 484–486 complex computations of passive dendritic trees, 481–482 dendrodendritic interactions between axonal cells, 481 depolarizing and hyperpolarizing conductance interactions, 484 electrotonics, see also Cable theory active conductances and relation to cable properties, 109 compartmentalization of electrotonic and biochemical properties, 109–110 nonlinear interactions of synaptic conductances, 108–109 properties, 110 ion channel distribution, 157 morphology, 1–2, 5, 35–36, 479–480 Nissl substance, 35 plasticity, 35 spines microintegrative function, 494–495 plasticity, 526 structure, 2–3 subthreshold dendritic activity, 481 voltage-gated computations, 485 voltage-gated channels in dendritic integration medium spiny cells, 492 Purkinje cells, 490 pyramidal neurons, 490–492 multiple impulse initiation site dynamic control, 492–494 information processing overview, 479–480, 495–496 Depression, catecholamine-degrading enzyme inhibitors in treatment, 260 Diacylglycerol (DAG) signal transduction, 336, 345–346 sources, 345–346 DNase I, actin binding, 52 Dopamine, see Catecholamines Dopamine ␤-hydroxylase (DBH), catecholamine biosynthesis, 255–256 Dopamine receptors classification, 328 pharmacology, 328 Double bouquet cell classes, cortical distribution, Dynamin, synaptic vesicle recycling, 219 Dynein ATPase inhibitor sensitivity, 55 microtubule association, 57 Dystrophin, 51 E Electrotonic spead, see Cable theory Enteric plexus neurons, 11–12 neurotransmitters, 12 Ependymoglial cell, gap junctions, 446 Epilepsy, gap junctions in neuropathology, 448–449 Epinephrine, see Catecholamines Excitable membrane modeling, see Membrane excitability models Eyeblink conditioning, see Classical conditioning F Facilitation, see Synaptic facilitation Fear conditioning, see Classical conditioning FitzHugh–Nagumo model, 192 Fluorescence recovery after photobleaching (FRAP), 398 Flux control coefficient (FCC), 412–413 fMRI, see Functional magnetic resonance imaging Fos, gene expression regulation, 382 FRAP, see Fluorescence recovery after photobleaching Functional magnetic resonance imaging (fMRI), principles, 71, 73 G GABA, see ␥-Aminobutyric acid GABAA chloride channel, 311 glycine receptor homology, 312 pharmacology, 311–312, 469 structure, 310–311 GABAB pharmacology, 469 types and functions, 330 GAD, see Glutamic acid decarboxylase Gap junction astrocyte syncytium, 446–448 calcium flux mediation, 437, 439 chemical transmission comparison directionality, 435 plasticity, 437 speed, 435–436 synaptic inhibition, 436 connexins developmental regulation of expression, 444 gap junction composition effects on properties, 441–442 homology, 435 mutation in disease, 434 structure, 435 types, 434–435, 439 definition, 432–433 gating ligands, 441 voltage, 440–441 glial cell connectivity astrocytes, 445 ependymoglial cells, 446 leptomeningeal cells, 445 oligodendrocytes, 445 Schwann cells, 445 history of study, 431–432 neuronal connectivity, 442–444 permeability, 437 Byrne_IDX(575-584).qxd 9/3/03 11:20 AM 578 Gap junction (continued) phosphorylation, 441 selective affinity of connexons, 442 structure, 433–435 Gelsolin, 51–52 Gene expression regulation chromatin modification, 375–376, 378 cis versus trans-regulating factors, 371–372 co-activators, 375–376, 378 co-repressors, 375–376, 378 cytokines in regulation, 383 growth factors in regulation, 383 neuron-specific expression, 378 nuclear receptor mechanisms, 383–386 posttranscriptional regulation, 386, 388 promoters binding proteins, 372 structure, 372, 374 signal-regulated transcription AP-1, 381–382 calcium-calmodulin-dependent protein kinase, 380 CREB, 380–381 Fos, 382 Jun, 382–383 mitogen-activated protein kinase, 382–393 nuclear factor-␬B, 380 overview, 371–372, 378–380 transcription factors dimerization, 374–375 domains, 374–375 transcription overview, 372 Glial cells, see Neuroglia Glucose brain cell-specific uptake and metabolism, 79–80 brain utilization rate, 67–68 compartmentalization of uptake, 82–83 glutamate stimulation of uptake in astrocytes, 80–83 imaging of metabolism in brain, 71–73, 80 metabolism, 67–68, 73–75 Glucose transporters (GLUTs) blood–brain barrier, 26 types in brain, 78–79 Glutamate astrocyte metabolism, 84–87 biosynthesis, 2688–269 excitatory neurotransmission, 268 inactivation, 270 release regulation, 270 reuptake, 84 stimulation of glucose uptake in astrocytes, 80–83 vesicular transporter, 269–270 Glutamate receptors assembly and subunit diversity, 313–314, 317–318 classification, 312 evolutionary relationships, 312–313 history of study, 313 Page 578 INDEX ionotropic receptors, see Amino-3hydroxy-5-methylisoxazoleproprionic acid receptors; Kainate receptors; N-Methyl-D-aspartate receptors metabotropic receptors long-term potentiation induction, 515–516 overview, 329–330 RNA splicing and editing of subunits, 314–315, 317 structure, 315 Glutamic acid decarboxylase (GAD), ␥-aminobutyric acid biosynthesis, 267 GLUTs, see Glucose transporters Glycine receptor chloride channel, 312 GABAA homology, 312 Glycogen astrocyte stores, 83 metabolism coupling with neuronal activity, 83 neurotransmitter regulation of metabolism in astrocytes, 83–84 Glycolysis, 67–68, 73 Goldman–Hodgkin–Katz equation, 120 Golgi apparatus cis-Golgi network, 39 coat protein roles in protein transport, 40 endocytosis and membrane cycling, 41–42 trans-Golgi network, 39, 41–43 vesicle fusion, 40 GPCR, see G protein-coupled receptor G protein GTPase activity, 337–338, 343 ion channel modulation, 148–149 subunit functions in coupled receptor activation ␣-subunit, 338, 341 ␤␥-subunits, 341 G protein-coupled receptor (GPCR), see also specific receptors activation, 318–319, 321–322 desensitization downregulation, 325–326 overview, 323 phosphorylative modulation, 324–325 sequestration, 325–326 disulfide bonds, 326 G protein coupling activation transduction sites, 321–322 neurotransmitter affinity effects, 322–323 sites, 321 specificity and potency of activation, 323 glycosylation, 326 ionotropic receptor interactions, 326 metabotropic glutamate receptors, 329–330 neurotransmitter binding conformational change and G protein activation, 320–321 site localization, 320 oligomerization, 322 peptide receptors, 330–331 signal transduction adenylyl cyclase fine-tuning of cyclic AMP, 343–345 advantages in neurotransmission, 352–353 calcium, 348 complexity, 339–340 experimental manipulation, 341–342 G protein cycle, 337–338 guanylyl cyclases, 349–351 ion channel modulation, 351–352 overview, 335–337 phosphodiesterases, 351 phospholipids, 345–348 requirements, 335 response specificity, 342–343 structure, 319–320, 322, 326, 331 Guanylate synthase nitric oxide modulation, 289–290, 349–351 types, 351 H Hair cell, features, 10–11 Hebbian rule, long-term potentiation, 508–510, 521 Hepatic encephalopathy, metabolic features, 85 Hill function, allosteric interaction modeling, 400–401 Hindmarsh–Rose model, 193 Hippocampus brain slice studies in learning and memory advantages, 504–505 Schaeffer collateral/commissural synapses, 505 eyeblink conditioning role, 544–547 fear conditioning role, 557–558 Hodgkin–Huxley model action potential simulation, 391–392 complexity of equations, 179 components of membrane current, 162–165 computation of equation solutions, 174–175 equivalent electrical circuit, 161–162 instantaneous current–voltage relationship, 164–165 limitations, 177 parameter modification in equations, 172 patch-clamped membranes, 178 potassium conductance characterization, 172–173 simplification, 411 simulations, 173, 175–177 sodium conductance characterization, 169–172 Byrne_IDX(575-584).qxd 9/3/03 11:20 AM Page 579 INDEX time and voltage dependency of ion conductances, 165–169 total membrane current, 173 two-dimensional reduction, 180, 182 voltage-clamp studies, 122–124, 161, 179 Hyperpolarization definition, 115 dendrite depolarizing and hyperpolarizing conductance interactions, 484 ion flux, 118–119 ionic current activation in rhythmic activity, 137 membrane potential ion distribution, 118–119 Inositol trisphosphate (IP3) calcium mobilization, 347 signal transduction, 336, 345, 347 termination of signal, 347–348 J Jellyfish, ion channel studies, 135 Jun, gene expression regulation, 382–383 K Kainate receptors assembly and subunit diversity, 313–314 functions, 315–316 RNA splicing and editing of subunits, 314–315 structure, 315 Katz model, see Quantal analysis Ketone bodies, brain utilization for energy, 68–69 Kinesin discovery, 55 mechanism of action, 55–56 structure, 55 I L Intermediate filament glutamate region, 53–54 interaction of cytoskeletal systems, 54–55 neurofilament triplet proteins, 53–54 packing, 53 pathology, 54 structure, 52 types, 52–54 Interneuron, see Basket cell; Bipolar neuron; Chandelier cell; Clutch cell; Double bouquet cell; Spiny stellate cell Ion channels, see also specific channels calcium modulation, 147–148 classification, 141, 143–144 distribution in neurons, 154–157 functional overlap, 144 G protein modulation, 351–352 inactivation mechanisms, 126, 129 ion binding sites, 150–152 ion selectivity, 141, 149–154 membrane potential maintenance, 120–121 metabolic modulation, 149 multiple ions in a pore, 150–152 mutations in disease, 127–128 neurotransmitter modulation, 148–149 noise in quantal analysis, 226 second messenger integration of signaling, 149 voltage gating functions, 144 inactivation types C-type, 147 N-type, 146 P-type, 146–147 S4 segment as voltage sensor, 144–146 Ionotropic receptors, types, 299–300 IP3, see Inositol trisphosphate Learning and memory Aplysia studies activity-dependent neuromodulation, 537–538 advantages, 531 intermediate-term sensitization, 536–537 long-term sensitization, 535 operant conditioning of feeding behavior, 539–540 short-term sensitization, 533–535 siphon–gill withdrawal reflexes, 531–533 tail–siphon withdrawal reflexes, 532–533 arthropod species for study, 542 associative learning, 529 Caenorhabditis elegans studies, 543 classical conditioning studies, see Classical conditioning gastropod mollusk species for study, 541–542 leech studies, 542 mechanisms, see Long-term depression; Long-term potentiation nonassociative learning, 530 prospects for study, 562–563 synaptic strength change and complex memory storage, 560–562 Leptomeningeal cell, gap junctions, 445 Long-term depression (LTD) definition, 521 depotentiation, 524 functions long-term potentiation saturation problem at excitatory synapses, 521–523 synaptic encoding in inhibitory neurons, 523 mechanisms 579 amino-3-hydroxy-5-methylisoxazoleproprionic acid receptor, 524–525 calcium flux, 524 cerebellar cortex, 525 N-methyl-D-aspartate receptor, 524–525 telecephalon, 524–525 overview, 499–500 Long-term potentiation (LTP) associativity, 501–503 Bienstock–Cooper–Munro rule, 526 brain slice studies confocal laser scanning microscopy with whole-cell recording, 506–508 hippocampus advantages, 504–505 Schaeffer collateral/commissural synapses, 505 mossy fibers in CA3, 505 novel preparations, 506 optical studies, 506 origins, 503–504 brain-derived neurotrophic factor role, 294 cooperativity, 501 definition, 235 expression postsynaptic changes glutamate receptor responses, 519–520 unsilencing of synapses, 519–520 presynaptic changes electron microscopy studies, 519 neurotransmitter release, 516–518 pharmacological analysis, 518–519 Hebbian mechanism of synaptic plasticity, 508–510 history of study, 499–500, 503–504 induction mechanisms calcium, 510 glutamate receptors, 510 metabotropic glutamate receptors, 515–516 N-methyl-D-aspartate receptor induction and modeling, 510–514 N-methyl-D-aspartate receptorindependent induction, 514–515 voltage-dependent calcium channels, 515 maintenance, gene expression and protein synthesis, 520–521 neuropharmacological linkages with information storage, 527 persistence, 500–501 rapid induction, 500–501 synapse specificity, 503 transgenic mouse studies, 527–528 LTD, see Long-term depression LTP, see Long-term potentiation Lysosome functions, 43 hereditary diseases, 43 protein trafficking, 43–44 Byrne_IDX(575-584).qxd 9/3/03 11:20 AM 580 Page 580 INDEX M mAChR, Muscarinic acetylcholine receptor Mannose, brain utilization for energy, 69 MAO, see Monoamine oxidase MAPK, see Mitogen-activated protein kinase MCA, see Metabolic control analysis Medium-sized spiny cell morphology, voltage-gated channels in dendritic integration, 492 Membrane excitability models, see also Hodgkin–Huxley model FitzHugh–Nagumo model, 192 geometric analysis action potential trajectory in the phase plane, 182, 185–187 advantages, 179–180 bifurcation, 187–188 bistability, 187–189 bursting activity, dynamical underpinnings, 189–191, 193–194 nonlinear dynamical systems, fixed points and bifurcations, 183–185 two-dimensional reduction of Hodgkin–Huxley model, 180, 182 Hindmarsh–Rose model, 193 Morris–Lecar model, 192–193 Membrane potential ion distribution concentrations and equilibrium potentials in neuron systems, 117 differential distribution, 116 hyperpolarization versus depolarization, 118–119 ion pump maintenance, 120–121 passive distribution, 116–118 Nernst equation, 118 resting membrane potential Goldman–Hodgkin–Katz equation, 120 ion contributions, 119 neuron type specificity, 120 Memory, see Learning and memory MET, see Morpho-electrtonic transform Metabolic control analysis (MCA), 412–413, 426 N-Methyl-D-aspartate (NMDA) receptors assembly and subunit diversity, 317–318 calmodulin binding, 318 gating, 316 long-term depression role, 524–525 long-term potentiation induction induction and modeling, 510–514 pharmacology, 316 RNA splicing of subunits, 317 structure, 315 subunit homology with other glutamate receptors, 316 Michaelis–Menten equation, 399, 411 Microfilament actin genes, 50–51 capping proteins, 51 functions, 50 interacting proteins, 51–52 interaction of cytoskeletal systems, 54–55 structure, 47 Microglia development, 21 immune response mediation, 21 morphology, 21 reactive microglia, 21–22 Microtubule associated proteins, 49–50, 57 axons, 50 dynamics, 50 functions, 48 interaction of cytoskeletal systems, 54–55 motor proteins, 49, 55–58 structure, 47–48 tubulin modifications, 48 Mitochondria, protein targeting, 44–45 Mitogen-activated protein kinase (MAPK) gene expression regulation, 382–393 modeling of cascade, 404–405, 414 Monoamine oxidase (MAO) catecholamine inactivation, 258–259 inhibitors in neuropsychiatric disorder management, 260 Monod–Wyman–Changeaux allosteric theory, 400 Morpho-electrotonic transform (MET), 106 also Morris–Lecar model, 192–193 Muscarinic acetylcholine receptor (mACHR) functions, 326–327 types, 327 Myelin sheath action potential propagation speed effects, 125 composition, 15 internodes, 14 myelination program in development, 13 nerve conduction facilitation, 13, 101–102 P0 function, 15–16 peripheral myelin protein-22 mutations in Charcot–Marie–Tooth disease, 17 Myosin ATPase inhibitor sensitivity, 55 structure myosin I, 58 myosin II, 57–58 types, 57–58 N nAChR, see Nicotinic acetylcholine receptor Nernst equation, 118 Nerve growth factor (NGF) neurotransmitter functions, 293–294 storage and release, 292–293 synthesis, 292 Neuroglia, see also Astrocyte; Microglia; Myelin sheath; Oligodendrocyte; Schwann cell cytoskeleton, see Cytoskeleton definition, 13 energy consumption, 77 gap junctions astrocytes, 445 ependymoglial cells, 446 leptomeningeal cells, 445 oligodendrocytes, 445 Schwann cells, 445 tumors, 451–452 myelin synthesis, 13–19 Neuromuscular junction active zone, 218 end plates, 198 neurotransmitter release, 199–200 quantal analysis, see Quantal analysis Neuron astrocyte–neuron metabolic unit, 87 cytoskeleton, see Cytoskeleton functions, 91 information processing theory, 91–92 interneurons, see Interneuron modeling, see also Cable theory; Compartmental models relating passive and active potentials, 111 Web site resources, 93 morphology, 1–2 protein synthesis, see Protein synthesis pyramidal cell, see Pyramidal neuron spiny stellate cell, see Spiny stellate cell subcortical neurons medium-sized spiny cells, Purkinje cells, 10 spinal motor neurons, 10 substabtia nigra dopaminergic neurons, Neuropeptides coexistence with classic neurotransmitters, 286–287 gene, 285 inactivation, 286 receptor, 286 storage and release, 286 synthesis, 285–286 Neurotransmitter, see also specific transmitters classic neurotransmitters, 250 definitive criteria, 246, 248, 295 history of study, 245–246 nontransmitter roles, 275–276 peptide transmitters, see also Neuropeptides experimental approaches for study, 283, 285 inactivation, 283–284 precursor processing, 282 synthesis and storage, 281, 283 rationale for multiple transmitters afferent convergence on a common neuron, 274, 279–280 colocalization of neurotransmitters, 274–275, 280 fast versus slow responses of target neurons, 275, 281 release from different neuron processes, 275, 280 Byrne_IDX(575-584).qxd 9/3/03 11:20 AM Page 581 INDEX synaptic specializations versus nonjunctional appositions between neurons, 275, 280–281 receptors, see specific receptors steps in neurotransmission biosynthesis, 248 inactivation and termination of action, 249 peptides versus classic neurotransmitters, 281, 283 receptor binding, 248–249 release, 248 storage, 248 Neurotransmitter release, see also Quantal analysis; Synaptic vesicle calcium in synapse exocytosis binding features high-affinity binding for slow transmitter secretion, 207–208 low-affinity binding for triggering, 206–207 microdomains in release, 204, 206 mobilization of vesicles to docking sites, 207 slow and fast transmitter corelease from same neuron terminal, 208 triggering, 203–204 catecholamines, 257–258 long-term potentiation expression, 516–518 quantal release, 197–199 rapidity, 209 synaptic membrane proteins in fusion docking and priming of vesicles, 217–218 genetic screening, 212, 214 identification from purified vesicles, 211–212 NSF, 217 Rab3, 217 SNAP-25, 214, 216–217 SNARE complex, 214–217 synapsin, 218 synaptobrevin, 214–215, 217 synaptotagmin, 219 syntaxin, 214 topology, 209–210 types and functions, 211 Neurotrophins neurotransmitter functions, 293–294 storage and release, 292–293 synthesis, 292 types, 291 NF-␬B, see Nuclear factor-kB NGF, see Nerve growth factor Nicotinic acetylcholine receptor (nAChR) assembly, 307 desensitization history of study, 300–301 phosphorylation, 307–308 structure acetylcholine binding sites, 305 architecture, 301 conformational change on opening, 305–306 ion selectivity and current flow relationships, 303 ionotropic receptor homology, 309–310 membrane-spanning segments, 301 neuromuscular junction versus Torpedo receptors, 306 neuronal subunit types and diversity, 309–310 Xenopus oocyte expression studies, 308 Nissl substance, 31–32, 35 Nitric oxide (NO) guanylate synthase modulation, 289–290, 349–35 mechanism of neuronal effects, 289–290 modeling of synthesis, 413 neuronal activity coupling with blood flow, 70–71 neurotransmission, 287, 289 regulation of levels, 289 stability and inactivation, 289 synthesis, 289, 350 NMDA receptors, see N-Methyl-D-aspartate receptors NO, see Nitric oxide Norepinephrine, see Catecholamines NSF, 40, 217 Nuclear factor-␬B (NF-␬B), gene expression regulation, 380 O Oligodendrocyte gap junctions, 445 myelin synthesis, 13–14 P P0, function, 15–16 Parkinson’s disease (PD), catecholaminedegrading enzyme inhibitors in treatment, 260 Patch-clamp, 178, 461–462 PD, see Parkinson’s disease PDEs, see Phosphodiesterases Pentose phosphate pathway, 74–75 Perikaryon cytoskeleton, Nissl substance, 31–32 nuclei, 31 translational cytoplasm, 31 Peripheral myelin protein-22 (PMP22), mutations in Charcot–Marie–Tooth disease, 17 Peroxisome, protein targeting, 45–46 PFK, see Phosphofructokinase Phenylethanolamine N-methyltransferase (PNMT), catecholamine biosynthesis, 256 Phenylketonuria (PKU), features, 252–253 Phosphodiesterases (PDEs) cyclic GMP phosphodiesterase, 351 functions, 343 Phosphofructokinase (PFK), modeling, 404 581 Phosphoinositols, signal transduction, 347 Phospholipase C (PLC), G protein coupling, 345–346 Phospholipase D (PLD), signal transduction, 345–346 PKA, see Protein kinase A PKC, see Protein kinase C PKU, see Phenylketonuria PLC, see Phospholipase C PLD, see Phospholipase D PMP22, see Peripheral myelin protein-22 PNMT, see Phenylethanolamine N-methyltransferase POMC, see Proopiomelanocortin Positron emission tomography (PET), principles, 71–72, 82 Postsynaptic potentials (PSPs) classification, 459 excitatory versus inhibitory postsynaptic potentials, 197 integration recruitment, 475 spatial summation, 476 temporal summation, 475–476 ionotropic postsynaptic potentials dual-component potentials, 470–471 gating and kinetic analysis, 462–465 inhibitory postsynaptic potentials, 469–469 nonlinear current–voltage relationships, 467–468 null potential and slope of current–voltage relationships, 465–466 patch-clamp studies, 461–462 stretch reflex, 459–460 summation of single-channel currents, 466–467 metabotropic postsynaptic potentials, 472–473 Posttetanic potentiation (PTP) definition, 235 features, 500 Potassium channels ATP-sensitive channels, 149 calcium activation, 148 distribution in neurons, 154, 156 inwardly rectifying, 143 two-pore channels, 143 voltage gating, S4 segment as voltage sensor, 145–146 Potassium conductance, dendrites, 483–484 Potassium currents Hodgkin–Huxley model, 172–173 types and functions, 131–132 voltage sensitivity and kinetics, 132–134 PP-1, see Protein phosphatase-1 Promoter binding proteins, 372 structure, 372, 374 Proopiomelanocortin (POMC), processing, 282 Protein kinase A (PKA) cognitive kinase activity, 360–361 Byrne_IDX(575-584).qxd 9/3/03 11:20 AM 582 Protein kinase A (PKA) (continued) consensus target sequence, 356–357 history of study, 355 regulation, 355–356 signal transduction, 336, 368 spatial localization in regulation, 359–360 structure, 355–357 types, 357 Protein kinase C (PKC) activation, 359 cognitive kinase activity, 362 isoforms, 358–359 signal transduction, 358, 368 spatial localization in regulation, 359–360 translocation, 359 Protein kinases, see also specific kinases catalytic reaction, 353 cognitive kinases, 360–362 criteria for study, 367–368 functional overview, 353–355 long-term depression role, 524–525 long-term potentiation induction, 513–514 regulation, 354 signal transduction network integration, 365, 367 spatial localization in regulation, 359–360 structural homology, 355–356 substrate specificity, 354 tyrosine kinases in cell growth and differentiation, 362–363 Protein phosphatase-1 (PP-1) regulation, 364 structure, 364 Protein phosphatases, see also specific phosphatases criteria for study, 367–368 functional overview, 353–355 regulation, 354 signal transduction network integration, 365, 367 spatial localization in regulation, 359–360 substrate specificity, 354 types, 354, 363–364 Protein synthesis cotranslational modifications, 39 cytoplasmic protein compartmentalization, 46–47 Golgi transport cis-Golgi network, 39 coat protein roles in protein transport, 40 endocytosis and membrane cycling, 41–42 trans-Golgi network, 39, 41–43 vesicle fusion, 40 integral membrane proteins, 37–38 peripheral membrane protein synthesis and targeting, 37 rough endoplasmic reticulum, 37–39, 47 secretory protein pathway, 37–38 signal sequences, 38–39 transcriptional regulation, see Gene expression regulation Page 582 INDEX Pseudounipolar sensory neuron, dorsal root ganglia, 35, 36 PSP, see Postsynaptic potentials PTP, see Posttetanic potentiation Purinergic receptors, types and functions, 312, 328–329 Purkinje cell morphology, 10 voltage-gated channels in dendritic integration, 490 Pyramidal neuron excitatory inputs, excitatory outputs, morphology, 3–5 neocortical layer features, 4–5 voltage-gated channels in dendritic integration, 490–492 Q Quantal analysis binomial models, 223, 229–230 central nervous system synapses versus neuromuscular junction nonuniform release probabilities, 227 one-quantum release, 226 receptor sampling of different quantal contents, 227 spontaneous miniature postsynaptic signals, 227–229 coefficient of variation, 232–233 long-term potentiation expression, 516–518 Poisson model, 223, 229 quantal parameter estimation from evoked and spontaneous signals confidence intervals, 232 model discrimination, 230 noise deconvolution, 230 overview, 227–228 spontaneous miniature postsynaptic signals, 228–229 Q, 229 quantal parameter estimation from experimental manipulation of release probability, 233–235 rationale, 221 standard Katz model limiting considerations ion channel noise, 226 postsynaptic summation and signal distortion, 226 quantal uniformity, 224–226 rapid and synchronous transmitter release, 226 stationarity, 226 uniform and independent release probabilities, 226 overview, 221–222 quantal parameters n, 223–224, 227 p, 224, 227 Q, 222, 227, 229 R Rab Rab3, 217 SNARE regulation, 40 Retina, photoreceptors, 10–11 RNA polymerase II, 372 Rod, features, 10–11 S Saltatory conduction, 14, 125 Schizophrenia, catecholamine-degrading enzyme inhibitors in treatment, 260 Schwann cell gap junctions, 445 myelin synthesis, 15 Serotonin autoreceptor regulation of synthesis and release, 264 biosynthesis alternative tryptophan metabolic pathways, 262, 264 L-aromatic amino acid decarboxylase, 262 overview, 262 tryptophan hydroxylase, 262 cell distribution, 261 discovery, 261 inactivation enzymatic degradation, 265 reuptake, 264–265 receptors classification, 329 5-HT3 structure, 310 release from vesicles, 264 short-term sensitization role in Aplysia, 533, 537 storage in vesicles, 264 vesicular monoamine transporters, 264 shiverer mouse, 16–17 Signal transduction G protein-coupled receptors requirements, 335 adenylyl cyclase fine-tuning of cyclic AMP, 343–345 advantages in neurotransmission, 352–353 calcium, 348 complexity, 339–340 experimental manipulation, 341–342 G protein cycle, 337–338 guanylyl cyclases, 349–351 ion channel modulation, 351–352 overview, 335–337 phosphodiesterases, 351 phospholipids, 345–348 response specificity, 342–343 gene expression regulation AP-1, 381–382 calcium-calmodulin-dependent protein kinase, 380 CREB, 380–381 Fos, 382 Byrne_IDX(575-584).qxd 9/3/03 11:20 AM Page 583 583 INDEX Jun, 382–383 mitogen-activated protein kinase, 382–393 nuclear factor-␬B, 380 overview, 371–372, 378–380 modeling allosteric interactions and Hill functions, 400–401 bifurcation analysis, 402, 409 bistability, 402 cross-talk between pathways, 405–408 enzymatic reactions, 399–400 feedback interactions, 392, 400–401, 403–404 gene network modeling continuous method, 419–421 feedback loops, 421–425 logical-network method, 418–419 overview, 416–418 stochastic fluctuations, 425) intracellular transport of signaling molecules active transport considerations, 399 buffering considerations, 396–398 discretization of cellular space, 395 electrodiffusion modeling, 396 Euler’s method, 394–395 experimental validation, 398 ordinary differential equations, 394 passive diffusion, 393 positive feedback, 394 symmetry reduction of dimension number, 395–396 key control parameters, 410 levels of detail, 392 linear versus nonlinear systems, 391 metabolic control analysis, 412–413, 426 multienzyme complexes, 413–414 persistent oscillations in pathways, 401–402 quantitative versus qualitative models, 392, 409–410 random variability and stochastic fluctuations, 414–416, 425 sensitivity of model behavior to parameter changes, 409 separation of fast and slow processes, 411 ultrasensitivity, 404–405 SNAP, 40–41 SNAP-25, 214, 216–217, 220 SNARE complex, 40–41, 214–217, 220 Sodium channels ion selectivity, 152–154 structure, 126 toxins in electrophysiology studies, 126 voltage gating, S4 segment as voltage sensor, 144–145 Sodium currents Hodgkin–Huxley model, 169–172 transient versus persistent, 132 types and functions, 131 Sodium/potassium-ATPase activation and glucose utilization, 82 astrocytes, 81 Spectrin, 51 Spinal motor neuron pathology, 10 types, 10 Spiny stellate cell axons, cortical distribution, 5–6 dendrites, functions, 12–13 Steroid hormones neurosteroid metabolites, 294–295 neurotransmission, 295 synthesis in brain, 294–295 Substantia nigra, dopaminergic neurons, Synapse asymmetric versus symmetric, chemical synapse organization, 197 discovery, 245 fusion, see Neurotransmitter release plasticity experience effects, 526–527 Hebbian mechanism, 508–510 hormonal modification, 526–527 learning and memory, 525–527 metaplasticity, 526–527 short-term synaptic plasticity, 235–238 Synapsin, synaptic vesicle targeting, 63, 218 Synaptic depression definition, 235 mechanisms, 235–236 Synaptic facilitation calcium modulation, 236–237 definition, 235 features, 500 Synaptic potential generation and ion channel distribution, 157 integration, see Postsynaptic potentials Synaptic vesicle, see also Neurotransmitter release action potential coupling to fusion, 219 calcium in exocytosis binding features high-affinity binding for slow transmitter secretion, 207–208 low-affinity binding for triggering, 206–207 microdomains in release, 204, 206 mobilization of vesicles to docking sites, 207 slow and fast transmitter corelease from same neuron terminal, 208 membrane proteins in fusion docking and priming of vesicles, 217–218 genetic screening, 212, 214 identification from purified vesicles, 211–212 NSF, 217 Rab3, 217 SNAP-25, 214, 216–217 SNARE complex, 214–217 synapsin, 218 synaptobrevin, 214–215, 217 synaptotagmin, 219 syntaxin, 214 topology, 209–210 types and functions, 211 neurotransmitter packaging, 219–220 quantal analysis, see Quantal analysis quantal release of neurotransmitters, 197–199 recycling endocytosis, 220 histological tracers in study, 203 steps, 201–203 trafficking cycle, 208–209 transmitter cycle, 200, 202 vesicle membrane cycle, 200 Synaptobrevin, 214–215, 217, 220 Synaptotagmin, 219 Syntaxin, 214 T TCA cycle, see Tricarboxylic acid cycle TH, see Tyrosine hydroxylase Transcription, see Gene expression regulation Tricarboxylic acid (TCA) cycle, 67–68, 73–74 Tryptophan hydroxylase, serotonin biosynthesis, 262 Tubulin, see Microtubule Tyrosine hydroxylase (TH), catecholamine biosynthesis, 253–255 V VAChT, see Vesicular cholinergic transporter Vesicular cholinergic transporter (VAChT), 271 Vesicular monoamine transporters (VMATs), 256–257, 264 VMATs, see Vesicular monoamine transporters Voltage-clamp, see also Hodgkin–Huxley model action potential studies, 122–124 principles, 122 W Wernicke–Korsakoff syndrome, features, 76 Z Zonula occludens, 26 ... laminar distribution project to different regions of the brain Adapted with permission, from Jones (1984) The excitatory inputs to pyramidal neurons can be divided into intrinsic afferents, such... recurrent projections function to set up local excitatory patterns and coordinate multineuronal assemblies into an excitatory output Spiny Stellate Cells Are Excitatory Interneurons The other major excitatory... terminal region, where From Molecules to Networks Apical dendrite Axon Purkinje cell of cerebellar cortex Axon Pyramidal cell of cerebral cortex FIGURE 1.1 Typical morphology of projection neurons On