Chapter 1
An Invitation to Neurobiology 1
NATURE AND NURTURE IN BRAIN
FUNCTION AND BEHAVIOR 1
1.1 Human twin studies c...
Chapter 3
Signaling across Synapses 69
HOW IS NEUROTRANSMITTER RELEASE
CONTROLLED AT THE PRESYNAPTIC
TERMINAL? 69
3.1 ...
4.15 Bipolar cells are either depolarized or
hyperpolarized by light based on the
glutamate receptors they express 137
...
6.2 Ca2+ coordinates olfactory recovery
and adaptation 210
6.3 Odorants are represented by
combinatorial activation o...
7.3 Cell fates are diversified by asymmetric
cell division and cell–cell interactions 281
7.4 Transcriptional regulat...
8.11 Population activity of motor cortical
neurons can be used to control neural
prosthetic devices 349
HOW DOES THE BR...
9.23 Parental behavior is activated by mating
and regulated by specific populations of
hypothalamic neurons 405
9.24 ...
11.6 Microglia dysfunction contributes to
late-onset Alzheimer’s disease 474
11.7 How can we treat Alzheimer’s disea...
12.14 Photoreceptor neurons evolved in two
parallel paths 535
12.15 Diversification of cell types is a crucial
step in ...
13.26 Synaptic connections can be mapped
by physiological and optogenetic
methods	601
BEHAVIORAL ANALYSES 602
13.27 Stu...
Special Features
Box 1–1 The debate between Ramón y Cajal and Golgi: why do scientists make mistakes? 9
Box 1–2 Commo...
of 11

Pon detailed table-of-contents

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Published on: Mar 4, 2016
Published in: Education      
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Transcripts - Pon detailed table-of-contents

  • 1. Chapter 1 An Invitation to Neurobiology 1 NATURE AND NURTURE IN BRAIN FUNCTION AND BEHAVIOR 1 1.1 Human twin studies can reveal the contributions of nature and nurture 1 1.2 Examples of nature: Animals exhibit instinctive behaviors 3 1.3 An example of nurture: Barn owls adjust their auditory map to match an altered visual map 4 HOW IS THE NERVOUS SYSTEM ORGANIZED? 6 1.4 The nervous system consists of neurons and glia 7 1.5 Individual neurons were first visualized by Golgi staining in the late nineteenth century 8 1.6 Twentieth-century technology confirmed the neuron doctrine 10 1.7 In vertebrate neurons, information generally flows from dendrites to cell bodies to axons 11 1.8 Neurons use membrane potential changes and neurotransmitter release to transmit information 13 1.9 Neurons function in the context of specific neural circuits 15 1.10 Specific brain regions perform specialized functions 18 1.11 The brain uses maps to organize information 19 1.12 The brain is a massively parallel computational device 21 GENERAL METHODOLOGY 23 1.13 Observations and measurements are the foundations for discovery 23 1.14 Perturbation experiments establish causes and mechanisms 24 SUMMARY 25 FURTHER READING 25 Chapter 2 Signaling within Neurons 27 CELL BIOLOGICAL AND ELECTRICAL PROPERTIES OF NEURONS 28 2.1 Neurons follow the central dogma of molecular biology and rules of intracellular vesicle trafficking 28 2.2 While some dendritic and axonal proteins are synthesized from mRNAs locally, most are actively transported from the soma 30 2.3 The cytoskeleton forms the basis of neuronal polarity and directs intracellular trafficking 32 2.4 Channels and transporters move solutes passively or actively across neuronal membranes 34 2.5 Neurons are electrically polarized at rest because of ion concentration differences across the plasma membrane and differential ion permeability 38 2.6 Neuronal plasma membrane can be described in terms of electrical circuits 40 2.7 Electrical circuit models can be used to analyze ion flows across glial and neuronal plasma membrane 43 2.8 Passive electrical properties of neurons: electrical signals evolve over time and decay across distance 44 2.9 Active electrical properties of neurons: depolarization above a threshold produces action potentials 47 HOW DO ELECTRICAL SIGNALS PROPAGATE FROM THE NEURONAL CELL BODY TO ITS AXON TERMINALS? 49 2.10 Action potentials are initiated by depolarization-induced inward flow of Na+ 49 2.11 Sequential, voltage-dependent changes in Na+ and K+ conductances account for action potentials 50 2.12 Action potentials are all-or-none, are regenerative, and propagate unidirectionally in the axon 52 2.13 Action potentials propagate more rapidly in axons with larger diameters and in myelinated axons 53 2.14 Patch clamp recording enables the study of current flow across individual ion channels 57 2.15 Cloning of genes that encode ion channels allows their structure–function relationship to be studied 59 2.16 Crystal structures reveal the atomic bases of ion channel properties 62 SUMMARY 65 FURTHER READING 66 Contents Copyright © 2016 Garland Science. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher.
  • 2. Chapter 3 Signaling across Synapses 69 HOW IS NEUROTRANSMITTER RELEASE CONTROLLED AT THE PRESYNAPTIC TERMINAL? 69 3.1 Action potential arrival at the presynaptic terminal triggers neurotransmitter release 69 3.2 Neurotransmitters are released in discrete packets 70 3.3 Neurotransmitters are released when synaptic vesicles fuse with the presynaptic plasma membrane 72 3.4 Neurotransmitter release is controlled by Ca2+ entry into the presynaptic terminal 74 3.5 SNARE and SM proteins mediate synaptic vesicle fusion 75 3.6 Synaptotagmin serves as a Ca2+ sensor to trigger synaptic vesicle fusion 78 3.7 The presynaptic active zone is a highly organized structure 79 3.8 Neurotransmitters are efficiently cleared from the synaptic cleft by enzymatic cleavage or transport into presynaptic and glial cells 80 3.9 Synaptic vesicle recycling by endocytosis is essential for continual synaptic transmission 81 3.10 Synapses can be facilitating or depressing 83 3.11 The nervous system uses many neurotransmitters 85 HOW DO NEUROTRANSMITTERS ACT ON POSTSYNAPTIC NEURONS? 87 3.12 Acetylcholine opens a nonselective cation channel at the neuromuscular junction 88 3.13 The skeletal muscle acetylcholine receptor is a ligand-gated ion channel 90 3.14 Neurotransmitter receptors are ionotropic or metabotropic 91 3.15 AMPA and NMDA glutamate receptors are activated by glutamate under different conditions 93 3.16 The postsynaptic density is organized by scaffolding proteins 95 3.17 Ionotropic GABA and glycine receptors are Cl– channels that mediate inhibition 96 3.18 All metabotropic neurotransmitter receptors trigger G protein cascades 99 3.19 A GPCR signaling paradigm: β-adrenergic receptors activate cAMP as a second messenger 100 3.20 α and βγ G protein subunits trigger diverse signaling pathways that alter membrane conductance 102 3.21 Metabotropic receptors can act on the presynaptic terminal to modulate neurotransmitter release 104 3.22 GPCR signaling features multiple mechanisms of signal amplification and termination 106 3.23 Postsynaptic depolarization can induce new gene expression 106 3.24 Dendrites are sophisticated integrative devices 110 3.25 Synapses are strategically placed at specific locations in postsynaptic neurons 113 SUMMARY 116 FURTHER READING 118 Chapter 4 Vision 121 HOW DO RODS AND CONES DETECT LIGHT SIGNALS? 121 4.1 Psychophysical studies revealed that human rods can detect single photons 122 4.2 Electrophysiological studies identified the single-photon response of rods: light hyperpolarizes vertebrate photoreceptors 123 4.3 Light activates rhodopsin, a prototypical G-protein-coupled receptor 124 4.4 Photon-induced signals are greatly amplified by a transduction cascade 125 4.5 Light-triggered decline of cyclic-GMP level directly leads to the closure of cation channels 126 4.6 Recovery enables the visual system to respond to light continually 127 4.7 Adaptation enables the visual system to detect contrast over a wide range of light levels 129 4.8 Cones are concentrated in the fovea for high-acuity vision 130 4.9 Cones are less sensitive but faster than rods 131 4.10 Photoreceptors with different spectral sensitivities are needed to sense color 132 4.11 Humans have three types of cones 133 4.12 Cloning of the cone opsin genes revealed the molecular basis of color detection 134 4.13 Defects in cone opsin genes cause human color blindness 135 HOW ARE SIGNALS FROM RODS AND CONES ANALYZED IN THE RETINA? 135 4.14 Retinal ganglion cells use center–surround receptive fields to analyze contrast 136 CONTENTS Copyright © 2016 Garland Science. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher.
  • 3. 4.15 Bipolar cells are either depolarized or hyperpolarized by light based on the glutamate receptors they express 137 4.16 Lateral inhibition from horizontal cells constructs the center–surround receptive fields 138 4.17 Diverse retinal cell types and their precise connections enable parallel information processing 140 4.18 Direction-selectivity of RGCs arises from asymmetric inhibition by amacrine cells 142 4.19 Color is sensed by comparing signals from cones with different spectral sensitivities 143 4.20 The same retinal cells and circuits can be used for different purposes 145 HOW IS INFORMATION PROCESSED IN THE VISUAL CORTEX? 146 4.21 Retinal information is topographically represented in the lateral geniculate nucleus and visual cortex 146 4.22 Receptive fields of LGN neurons are similar to those of RGCs 148 4.23 Primary visual cortical neurons respond to lines and edges 149 4.24 How do visual cortical neurons acquire their receptive fields? 150 4.25 Cells with similar properties are vertically organized in the visual cortex 151 4.26 Information generally flows from layer 4 to layers 2/3 and then to layers 5/6 in the neocortex 154 4.27 Visual information is processed in parallel streams 157 4.28 Face recognition cells form a specialized network in the primate temporal cortex 159 4.29 Linking perception to decision and action: microstimulation of MT neurons biased motion choice 160 SUMMARY 163 FURTHER READING 164 Chapter 5 Wiring of the Visual System 167 HOW DO RETINAL GANGLION CELL AXONS FIND THEIR TARGETS? 167 5.1 Optic nerve regeneration experiments suggested that RGC axons are predetermined for wiring 168 5.2 Point-to-point connections between retina and tectum arise by chemoaffinity 169 5.3 The posterior tectum repels temporal retinal axons 171 5.4 Gradients of ephrins and Eph receptors instruct retinotectal mapping 172 5.5 A single gradient is insufficient to specify an axis 174 5.6 To cross, or not to cross: that is the question 178 HOW DO EXPERIENCE AND NEURONAL ACTIVITY CONTRIBUTE TO WIRING? 180 5.7 Monocular deprivation markedly impairs visual cortex development 180 5.8 Competing inputs are sufficient to produce spatial segregation at the target 182 5.9 Ocular dominance columns in V1 and eye-specific layers in LGN develop by gradual segregation of eye-specific inputs 183 5.10 Retinal neurons exhibit spontaneous waves of activity before the onset of vision 184 5.11 Retinal waves and correlated activity drive segregation of eye-specific inputs 185 5.12 Hebb’s rule: correlated activity strengthens synapses 187 5.13 A Hebbian molecule: the NMDA receptor acts as a coincidence detector 189 HOW DO MOLECULAR DETERMINANTS AND NEURONAL ACTIVITY WORK TOGETHER? 190 5.14 Ephrins and retinal waves act in parallel to establish the precise retinocollicular map 192 5.15 Ephrins and retinal waves also work together to establish the retinotopic map in the visual cortex 193 5.16 Different aspects of visual system wiring rely differentially on molecular cues and neuronal activity 195 VISUAL SYSTEM DEVELOPMENT IN DROSOPHILA: LINKING CELL FATE TO WIRING SPECIFICITY 197 5.17 Cell–cell interactions determine photoreceptor cell fates: R7 as an example 198 5.18 Multiple parallel pathways participate in layer-specific targeting of R8 and R7 axons 201 SUMMARY 203 FURTHER READING 204 Chapter 6 Olfaction, Taste, Audition, and Somatosensation 207 HOW DO WE SENSE ODORS? 207 6.1 Odorant binding leads to opening of a cyclic nucleotide-gated channel in olfactory receptor neurons 208 CONTENTS Copyright © 2016 Garland Science. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher.
  • 4. 6.2 Ca2+ coordinates olfactory recovery and adaptation 210 6.3 Odorants are represented by combinatorial activation of olfactory receptor neurons 210 6.4 Odorant receptors are encoded by many hundreds of genes in mammals 210 6.5 Polymorphisms in odorant receptor genes contribute to individual differences in odor perception 213 6.6 Each olfactory receptor neuron (ORN) expresses a single odorant receptor 214 6.7 ORNs expressing a given odorant receptor are broadly distributed in the nose 214 6.8 ORNs expressing the same odorant receptor project their axons to the same glomerulus 215 6.9 Olfactory bulb circuits transform odor representation through lateral  inhibition 217 6.10 Olfactory inputs are differentially organized in distinct cortical areas 218 HOW DO WORMS AND FLIES SENSE ODORS? 222 6.11 C. elegans encodes olfactory behavioral choices at the sensory neuron level 223 6.12 C. elegans sensory neurons are activated by odorant withdrawal and engage ON- and OFF-pathways 224 6.13 The olfactory systems in insects and mammals share many similarities 225 6.14 The antennal lobe transforms ORN input for more efficient representation by projection neurons 226 6.15 Odors with innate behavioral significance use dedicated olfactory processing channels 230 6.16 Odor representation in higher centers is stereotyped or stochastic depending on whether the center directs innate or learned behavior 231 TASTE: TO EAT, OR NOT TO EAT? 232 6.17 Mammals have five classic taste modalities: sweet, bitter, umami, salty, and sour 233 6.18 Sweet and umami are sensed by heterodimers of the T1R family of G-protein-coupled receptors 233 6.19 Bitter is sensed by a family of ~30 T2R G-protein-coupled receptors 234 6.20 Sour and salty tastes involve specific ion channels 236 6.21 Activation of specific taste receptor cells confers specific taste perceptions 236 AUDITION: HOW DO WE HEAR AND LOCALIZE SOUNDS? 238 6.22 Sounds are converted to electrical signals by mechanically gated ion channels in the stereocilia of hair cells 239 6.23 Sound frequencies are represented as a tonotopic map in the cochlea 240 6.24 Motor properties of outer hair cells amplify auditory signals and sharpen frequency tuning 243 6.25 Auditory signals are processed by multiple brainstem nuclei before reaching the cortex 245 6.26 In the owl, sound location is determined by comparing the timing and levels of sounds reaching two ears 246 6.27 Mechanisms of sound location in mammals differ from those in the owl 249 6.28 The auditory cortex analyzes complex and biologically important sounds 250 SOMATOSENSATION: HOW DO WE SENSE BODY MOVEMENT, TOUCH, TEMPERATURE, AND PAIN? 255 6.29 Many types of sensory neurons are used to encode diverse somatosensory stimuli 257 6.30 Merkel cells and some touch sensory neurons employ Piezo2 as a mechanotransduction channel 259 6.31 TRP channels are major contributors to temperature, chemical, and pain sensation 262 6.32 Sensation can be a product of central integration: the distinction of itch and pain as an example 264 6.33 Touch and pain signals are transmitted by parallel pathways to the brain 266 6.34 Pain is subjected to peripheral and central modulation 268 6.35 Linking neuronal activity with touch perception: from sensory fiber to cortex 269 SUMMARY 272 FURTHER READING 273 Chapter 7 Wiring of the Nervous System 277 HOW DOES WIRING SPECIFICITY ARISE IN THE DEVELOPING NERVOUS SYSTEM? 278 7.1 The nervous system is highly patterned as a consequence of early developmental events 278 7.2 Orderly neurogenesis and migration produce many neuronal types that occupy specific positions 280 CONTENTS Copyright © 2016 Garland Science. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher.
  • 5. 7.3 Cell fates are diversified by asymmetric cell division and cell–cell interactions 281 7.4 Transcriptional regulation of guidance molecules links cell fate to wiring decision 283 7.5 Crossing the midline: Combinatorial actions of guidance receptors specify axon trajectory choice 286 7.6 Crossing the midline: Axons switch responses to guidance cues at intermediate targets 288 7.7 The cell polarity pathway participates in determining whether a neuronal process becomes an axon or a dendrite 290 7.8 Local secretory machinery is essential for dendrite morphogenesis and microtubule organization 292 7.9 Homophilic repulsion enables self-avoidance of axonal and dendritic branches 293 7.10 Subcellular site selection of synaptogenesis uses both attractive and repulsive mechanisms 295 7.11 Bidirectional trans-synaptic communication directs the assembly of synapses 297 7.12 Astrocytes stimulate synapse formation and maturation 299 7.13 Activity and competition refine neuromuscular connectivity 300 7.14 Developmental axon pruning refines wiring specificity 301 7.15 Neurotrophins from target cells support the survival of sensory, motor, and sympathetic neurons 302 ASSEMBLY OF OLFACTORY CIRCUITS: HOW DO NEURAL MAPS FORM? 305 7.16 Neural maps can be continuous, discrete, or a combination of the two 305 7.17 In mice, odorant receptors instruct ORN axon targeting by regulating expression of guidance molecules 307 7.18 ORN axons sort themselves by repulsive interactions before reaching their target 309 7.19 Activity-dependent regulation of adhesion and repulsion refines glomerular targeting 310 7.20 Drosophila projection neurons’ lineage and birth order specify the glomeruli that their dendrites target 312 7.21 Graded determinants and discrete molecular labels control the targeting of projection neuron dendrites 313 7.22 Sequential interactions among ORN axons limit their target choice 314 7.23 Homophilic matching molecules instruct connection specificity between synaptic partners 315 HOW DO ~20,000 GENES SPECIFY 1014 CONNECTIONS? 316 7.24 Some genes can produce many protein variants 316 7.25 Protein gradients can specify different connections 318 7.26 The same molecules can serve multiple functions 318 7.27 The same molecules can be used at multiple times and places 318 7.28 Combinatorial use of wiring molecules can reduce the number of wiring molecules needed 319 7.29 Dividing wiring decisions into multiple steps can conserve molecules and increase fidelity 319 7.30 Many connections do not need to be specified at the level of individual synapses or neurons 320 7.31 Wiring can be instructed by neuronal activity and experience 320 SUMMARY 321 FURTHER READING 322 Chapter 8 Motor and Regulatory Systems 325 HOW IS MOVEMENT CONTROLLED? 326 8.1 Muscle contraction is mediated by sliding of actin and myosin filaments and is regulated by intracellular Ca2+ 326 8.2 Motor units within a motor pool are recruited sequentially from small to large 329 8.3 Motor neurons receive diverse and complex input 330 8.4 Central pattern generators coordinate rhythmic contraction of muscles during locomotion 332 8.5 Intrinsic properties of neurons and their connection patterns produce rhythmic output in a model central pattern generator 334 8.6 The spinal cord uses multiple central pattern generators to control locomotion 336 8.7 The brainstem contains specific motor control nuclei 338 8.8 The cerebellum is required for fine control of movement 340 8.9 The basal ganglia participate in initiation and selection of motor programs 343 8.10 Voluntary movement is controlled by the population activity of motor cortical neurons in a dynamical system 346 CONTENTS Copyright © 2016 Garland Science. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher.
  • 6. 8.11 Population activity of motor cortical neurons can be used to control neural prosthetic devices 349 HOW DOES THE BRAIN REGULATE THE FUNCTIONS OF INTERNAL ORGANS? 351 8.12 The sympathetic and parasympathetic systems play complementary roles in regulating body physiology 351 8.13 The autonomic nervous system is a multilayered regulatory system 353 8.14 The hypothalamus regulates diverse basic body functions via homeostasis and hormone secretion 354 HOW IS EATING REGULATED? 356 8.15 Hypothalamic lesion and parabiosis experiments suggested that eating is inhibited by a negative feedback signal from the body 356 8.16 Studies of mouse mutants led to the discovery of the leptin feedback signal from adipose tissues 357 8.17 POMC and AgRP neurons in the arcuate nucleus are central regulators of eating 358 8.18 Multiple feedback signals and neural pathways act in concert to regulate eating 360 HOW ARE CIRCADIAN RHYTHMS AND SLEEP REGULATED? 362 8.19 Circadian rhythms are driven by an auto- inhibitory transcriptional feedback loop that is conserved from flies to mammals 362 8.20 Entrainment in flies is accomplished by light-induced degradation of circadian rhythm regulators 365 8.21 Pacemaker neurons in the mammalian suprachiasmatic nucleus integrate input and coordinate output 366 8.22 Sleep is widespread in the animal kingdom and exhibits characteristic electroencephalogram patterns in mammals 367 8.23 The mammalian sleep–wake cycle is regulated by multiple neurotransmitter and neuropeptide systems 369 8.24 Why do we sleep? 372 SUMMARY 374 FURTHER READING 375 Chapter 9 Sexual Behavior 377 HOW DO GENES SPECIFY SEXUAL BEHAVIOR IN THE FLY? 378 9.1 Drosophila courtship follows a stereotyped ritual that is instinctive 378 9.2 Fruitless (Fru) is essential for many aspects of sexual behavior 379 9.3 A sex-determination hierarchy specifies sex-specific splicing of Fru that produces male-specific FruM 379 9.4 Expression of FruM in females is sufficient to produce most aspects of male courtship behavior 380 9.5 Activity of FruM neurons promotes male courtship behavior 381 9.6 FruM sensory neurons process mating-related sensory cues 382 9.7 FruM central neurons integrate sensory information and coordinate the behavioral sequence 384 9.8 FruM neurons in the ventral nerve cord regulate mating-related behavioral output 385 9.9 FruM-equivalent neurons in females promote female receptivity to courtship 386 9.10 FruM and Doublesex (Dsx) regulate sexually dimorphic programmed cell death 386 9.11 Dsx and FruM control sexually dimorphic neuronal wiring 389 9.12 Even innate behavior can be modified by experience 390 HOW ARE MAMMALIAN SEXUAL BEHAVIORS REGULATED? 390 9.13 The Sry gene on the Y chromosome determines male differentiation via testosterone production 393 9.14 Testosterone and estradiol are the major sex hormones 393 9.15 Early exposure to testosterone causes females to exhibit male-typical sexual behavior 395 9.16 Testosterone exerts its organizational effect mainly through the estrogen receptors in rodents 396 9.17 Dialogues between the brain and gonads initiate sexual maturation at puberty and maintain sexual activity in adults 396 9.18 Sex hormones specify sexually dimorphic neuronal numbers by regulating programmed cell death 398 9.19 Sex hormones also regulate sexually dimorphic neuronal connections 399 9.20 Sexually dimorphic nuclei define neural pathways from olfactory systems to the hypothalamus 400 9.21 Whereas the main olfactory system is essential for mating, the accessory olfactory system discriminates sex partners in mice 401 9.22 The same neuronal population can control multiple behaviors in females and males 402 CONTENTS Copyright © 2016 Garland Science. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher.
  • 7. 9.23 Parental behavior is activated by mating and regulated by specific populations of hypothalamic neurons 405 9.24 Two neuropeptides, oxytocin and vasopressin, regulate pair bonding and parental behavior 407 SUMMARY 410 FURTHER READING 412 Chapter 10 Memory, Learning, and Synaptic Plasticity 415 PRELUDE: WHAT IS MEMORY, AND HOW IS IT ACQUIRED BY LEARNING? 415 10.1 Memory can be explicit or implicit, short-term, or long-term: Insights from amnesic patients 415 10.2 Hypothesis I: Memory is stored as strengths of synaptic connections in neural circuits 417 10.3 Hypothesis II: Learning modifies the strengths of synaptic connections 420 HOW IS SYNAPTIC PLASTICITY ACHIEVED? 420 10.4 Long-term potentiation (LTP) of synaptic efficacy can be induced by high-frequency stimulation 421 10.5 LTP at the hippocampal CA3 → CA1 synapse exhibits input specificity, cooperativity, and associativity 421 10.6 The NMDA receptor is a coincidence detector for LTP induction 423 10.7 Recruitment of AMPA receptors to the postsynaptic surface is the predominant mechanism of LTP expression 423 10.8 CaMKII auto-phosphorylation creates a molecular memory that links LTP induction and expression 425 10.9 Long-term depression weakens synaptic efficacy 426 10.10 Spike-timing-dependent plasticity can adjust synaptic efficacy bidirectionally 428 10.11 Dendritic integration in the postsynaptic neuron also contributes to synaptic plasticity 428 10.12 Postsynaptic cells can produce retrograde messengers to regulate neurotransmitter release by their presynaptic partners 429 10.13 Long-lasting changes of connection strengths involve formation of new synapses 431 WHAT IS THE RELATIONSHIP BETWEEN LEARNING AND SYNAPTIC PLASTICITY? 434 10.14 Animals exhibit many forms of learning 434 10.15 Habituation and sensitization in Aplysia are mediated by changes of synaptic strength 437 10.16 Both short-term and long-term memory in Aplysia engage cAMP signaling 439 10.17 Olfactory conditioning in Drosophila requires cAMP signaling 441 10.18 Drosophila mushroom body neurons are the site of CS–US convergence for olfactory conditioning 442 10.19 In rodents, spatial learning and memory depend on the hippocampus 446 10.20 Many manipulations that alter hippocampal LTP also alter spatial memory 447 10.21 From correlation to causation: the synaptic weight matrix hypothesis revisited 449 WHERE DOES LEARNING OCCUR, AND WHERE IS MEMORY STORED IN THE BRAIN? 451 10.22 The neocortex contributes to long-term storage of explicit memory 451 10.23 The amygdala plays a central role in fear conditioning 454 10.24 Dopamine plays a key role in reward- based learning 456 10.25 Early experience can leave behind long-lasting memory traces to facilitate adult learning 459 SUMMARY 463 FURTHER READING 464 Chapter 11 Brain Disorders 467 ALZHEIMER’S DISEASE AND OTHER NEURODEGENERATIVE DISEASES 467 11.1 Alzheimer’s disease is defined by brain deposition of numerous amyloid plaques and neurofibrillary tangles 468 11.2 Amyloid plaques mainly consist of aggregates of proteolytic fragments of the amyloid precursor protein (APP) 469 11.3 Mutations in human APP and γ-secretase cause early-onset familial Alzheimer’s disease 470 11.4 Animal models offer crucial tools to investigate pathogenic mechanisms 472 11.5 An apolipoprotein E (ApoE) variant is a major risk factor for Alzheimer’s disease 473 CONTENTS Copyright © 2016 Garland Science. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher.
  • 8. 11.6 Microglia dysfunction contributes to late-onset Alzheimer’s disease 474 11.7 How can we treat Alzheimer’s disease? 475 11.8 Prion diseases are caused by propagation of protein-induced protein conformational change 477 11.9 Aggregation of misfolded proteins is associated with many neurodegenerative diseases 479 11.10 Parkinson’s disease results from death of substantia nigra dopamine neurons 480 11.11 α-Synuclein aggregation and spread are prominent features of Parkinson’s pathology 480 11.12 Mitochondrial dysfunction is central to the pathogenesis of Parkinson’s disease 482 11.13 Treating Parkinson’s disease: l-dopa, deep brain stimulation, and cell- replacement therapy 483 11.14 The various neurodegenerative diseases have common themes and exhibit unique properties 487 PSYCHIATRIC DISORDERS 487 11.15 Schizophrenia can be partially alleviated by drugs that interfere with dopamine function 488 11.16 Mood disorders have been treated by manipulating monoamine neurotransmitter metabolism 490 11.17 Modulating GABAergic inhibition can alleviate symptoms of anxiety disorders 491 11.18 Addictive drugs hijack the brain’s reward system by enhancing the action of VTA dopamine neurons 493 11.19 Human genetic studies suggest that many genes contribute to psychiatric disorders 495 NEURODEVELOPMENTAL DISORDERS 498 11.20 Intellectual disabilities and autism spectrum disorders are caused by mutations in many genes 499 11.21 Rett syndrome is caused by defects in MeCP2, a regulator of global gene expression 500 11.22 MeCP2 acts predominantly in post-mitotic neurons to regulate their maturation and function 502 11.23 Restoring MeCP2 expression in adulthood reverses symptoms in a mouse model of Rett syndrome 503 11.24 Fragile-X syndrome is caused by loss of an RNA-binding protein that regulates translation 504 11.25 Reducing mGluR signaling ameliorates fragile-X symptoms in animal models 505 11.26 Synaptic dysfunction is a common cellular mechanism that underlies neurodevelopmental and psychiatric disorders 506 11.27 Studies of brain disorders and basic neurobiology research advance each other 507 SUMMARY 510 FURTHER READING 511 Chapter 12 Evolution of the Nervous System 513 GENERAL CONCEPTS AND APPROACHES IN EVOLUTIONARY ANALYSIS 514 12.1 Phylogenetic trees relate all living organisms in a historical context 515 12.2 Cladistic analysis distinguishes processes of evolutionary change 517 12.3 Gene duplication, diversification, loss, and shuffling provide rich substrates for natural selection 519 12.4 Altering patterns of gene expression is an important mechanism for evolutionary change 520 12.5 Natural selection can act on multiple levels in the developing and adult nervous systems to enhance fitness 521 EVOLUTION OF NEURONAL COMMUNICATION 522 12.6 Ion channels appeared sequentially to mediate electrical signaling 523 12.7 Myelination evolved independently in vertebrates and large invertebrates 524 12.8 Synapses likely originated from cell junctions in early metazoans 525 12.9 Neurotransmitter release mechanisms were co-opted from the secretory process 526 EVOLUTION OF SENSORY SYSTEMS 527 12.10 G-protein-coupled receptors (GPCRs) are ancient chemosensory receptors in eukaryotes 530 12.11 Chemosensory receptors in animals are predominantly GPCRs 532 12.12 Two distinct families of ligand-gated ion channels cooperate to sense odors in insects 532 12.13 Retinal- and opsin-based light-sensing apparatus evolved independently at least twice 534 CONTENTS Copyright © 2016 Garland Science. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher.
  • 9. 12.14 Photoreceptor neurons evolved in two parallel paths 535 12.15 Diversification of cell types is a crucial step in the evolution of the retinal circuit 538 12.16 Trichromatic color vision in primates originated from variations and duplications of a cone opsin gene 540 12.17 Introducing an extra cone opsin in dichromatic animals enables superior spectral discrimination 542 EVOLUTION OF NERVOUS SYSTEM STRUCTURE AND DEVELOPMENT 543 12.18 All bilaterians share a common body plan specified by conserved developmental regulators 544 12.19 Eye development is controlled by evolutionarily conserved transcription factors 546 12.20 The mammalian neocortex underwent rapid expansion recently 547 12.21 The size of the neocortex can be altered by modifying the mechanisms of neurogenesis 548 12.22 Cortical area specialization can be shaped by input patterns 550 SUMMARY 553 FURTHER READING 555 Chapter 13 Ways of Exploring 557 ANIMAL MODELS IN NEUROBIOLOGY RESEARCH 557 13.1 Some invertebrates provide large, identifiable neurons for electrophysiological investigations 557 13.2 Drosophila and C. elegans allow sophisticated genetic manipulations 558 13.3 Diverse vertebrate animals offer technical ease or special faculties 559 13.4 Mice, rats, and nonhuman primates are important models for mammalian neurobiology research 560 13.5 Human studies are facilitated by a long history of medicine and experimental psychology and by the recent genomic revolution 560 GENETIC AND MOLECULAR TECHNIQUES 561 13.6 Forward genetic screens use random mutagenesis to identify genes that control complex biological processes 562 13.7 Reverse genetics disrupts pre-designated genes to assess their functions 563 13.8 RNA interference (RNAi)-mediated knockdown can also be used to assess gene function 567 13.9 Genetic mosaic analysis can pinpoint which cell is critical for mediating gene action 568 13.10 Transgene expression can be controlled in both space and time in transgenic animals 569 13.11 Transgene expression can also be achieved by viral transduction and other transient methods 571 13.12 Accessing specific neuronal types facilitates functional circuit dissection 572 13.13 Gene expression patterns can be determined by multiple powerful techniques 572 13.14 Genome sequencing reveals connections across species and identifies genetic variations that contribute to diseases 574 ANATOMICAL TECHNIQUES 575 13.15 Histological analyses reveal the gross organization of the nervous system 575 13.16 Visualizing individual neurons opens new vistas in understanding the nervous system 578 13.17 Fine structure studies can identify key facets of molecular organization within neurons 579 13.18 Mapping neuronal projections allows the tracking of information flow across different brain regions 582 13.19 Mapping synaptic connections reveals neural circuitry 584 RECORDING AND MANIPULATING NEURONAL ACTIVITY 586 13.20 Extracellular recordings can detect the firing of individual neurons 587 13.21 Intracellular and whole-cell patch recordings can measure synaptic input in addition to firing patterns 589 13.22 Optical imaging can measure the activity of many neurons simultaneously 591 13.23 Neuronal inactivation can be used to reveal which neurons are essential for circuit function and behavior 596 13.24 Neuronal activation can establish sufficiency of neuronal activity in circuit function and behavior 598 13.25 Optogenetics allows control of the activity of genetically targeted neurons with millisecond precision 599 CONTENTS Copyright © 2016 Garland Science. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher.
  • 10. 13.26 Synaptic connections can be mapped by physiological and optogenetic methods 601 BEHAVIORAL ANALYSES 602 13.27 Studying animal behavior in natural environments can reveal behavioral repertoires and their adaptive value 603 13.28 Studying behaviors in highly controlled conditions facilitates investigation of their neural basis 604 13.29 Behavioral assays can be used to evaluate the functions of genes and neurons and to model human brain disorders 606 SUMMARY AND PERSPECTIVES 608 FURTHER READING 610 GLOSSARY 612 INDEX CONTENTS Copyright © 2016 Garland Science. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher.
  • 11. Special Features Box 1–1 The debate between Ramón y Cajal and Golgi: why do scientists make mistakes? 9 Box 1–2 Commonly used neural circuit motifs 17 Box 2–1 How were kinesins discovered? 35 Box 2–2 A deeper look at R-C circuits 42 Box 2–3 Axon–glia interactions in health and disease 55 Box 2–4 Diverse ion channels for diverse functions 63 Box 3–1 Binomial distribution, Poisson distribution, and calculating neurotransmitter release probability 72 Box 3–2 From toxins to medicines 77 Box 3–3 G proteins are molecular switches 101 Box 3–4 Signal transduction and receptor tyrosine kinase signaling 107 Box 3–5 Electrical synapses 115 Box 4–1 Vision research uses diverse animal models 124 Box 4–2 Intrinsically photosensitive retinal ganglion cells have multiple functions 147 Box 4–3 Cracking neocortical microcircuits 155 Box 5–1 Molecular biology of axon guidance 174 Box 5–2 Cell biology and signaling at the growth cone 179 Box 5–3 Activity-dependent wiring of the rodent whisker-barrel system depends on the NMDA receptor 190 Box 6–1 The mammalian accessory olfactory system is specialized for detecting pheromones and predator cues 221 Box 6–2 The vestibular system senses movement and orientation of the head 253 Box 6–3 Mechanotransduction channels in worms and flies 260 Box 8–1 Neuromodulatory systems 370 Box 9–1 Bird song: nature, nurture, and sexual dimorphism 391 Box 9–2 Courtship in unisexual lizards 403 Box 9–3 An ancestral function of oxytocin/vasopressin-like neuropeptide in sexual behavior 409 Box 10–1 Synaptic tagging: maintaining input specificity in light of new gene expression 432 Box 10–2 Place cells, grid cells, and representations of space 444 Box 10–3 How to find an engram 450 Box 10–4 Microcircuits of the central amygdala 456 Box 10–5 Memory can be formed by the activation of random populations of cortical neurons 459 Box 11–1 Rational drug development to treat brain disorders 476 Box 11–2 Producing neurons from embryonic stem cells, induced pluripotent cells, and fibroblasts 485 Box 11–3 How to collect and interpret human genetics data for brain disorders 497 Box 11–4 Epilepsy is a disorder of neuronal network excitability 508 Box 12–1 When did the nervous system first emerge? 517 Box 12–2 Chemotaxis: from bacteria to animals 528 Box 12–3 Darwin and the evolution of the eye 537 Box 12–4 Transcription factor FoxP2 and the evolution of language 552 Box 13–1 Genome engineering by the CRISPR–Cas9 system 565 Box 13–2 Patch clamp recordings can serve many purposes 590 Box 13–3 From in vitro preparations to awake, behaving animals: a comparison of recording methods 594 Copyright © 2016 Garland Science. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher.