E-Book, Englisch, 334 Seiten
ISBN: 978-0-08-091989-8
Verlag: Elsevier Health Care - Major Reference Works
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)
The book starts by discussing the history of the young field of behavioral genetics, and it continues with a description of the fundamental functions and the organization of the nervous system. The book goes on to offer basic topics related to quantitative genetic principles, and it focuses on a wide range of commonly studied behaviors, including chemoreception, circadian activity and sleep, social behaviors, locomotion, learning and memory, and addiction. This book will be a valuable resource for future generations of scientists who focus on the field of behavioral genetics.
* Defines the emerging science of behavioral genetics
* Engagingly written by two leading experts in behavioral genetics
* Clear explanations of basic quantitative genetic, neurogenetic and genomic applications to the study of behavior
* Numerous examples ranging from model organisms to non-model systems and humans
* Concise overviews and summaries for each chapter
Autoren/Hrsg.
Weitere Infos & Material
1;Front Cover;1
2;Principles of Behavioral Genetics;4
3;Copyright Page;5
4;Contents;6
5;Preface;10
6;Chapter 1: Introduction and Historical Perspective;12
6.1;Overview;12
6.2;The Rise of the Modern Field of Behavioral Genetics;12
6.3;The Modern Evolutionary Synthesis;23
6.4;The Rise of Molecular Genetics;25
6.5;A Brief History of Neuroscience;27
6.6;The Emergence of Behavioral Genetics;29
6.7;Summary;31
6.8;Study Questions;31
6.9;Recommended Reading;32
7;Chapter 2: Mechanisms of Neural Communication;34
7.1;Overview;34
7.2;Transmission of Information in the Nervous System;34
7.3;The Resting Membrane Potential;35
7.4;The Mechanism of the Action Potential;36
7.5;Ion Channels, G-protein-coupled Receptors, and Signal Transduction;41
7.6;Summary;48
7.7;Study Questions;48
7.8;Recommended Reading;48
8;Chapter 3: Functional Organization of the Nervous System;50
8.1;Overview;50
8.2;The Organization of the Mammalian Nervous System;50
8.3;Communication between the Brain and the Periphery;52
8.4;Organization of the Nervous System in Insects;56
8.5;Neurotransmitters;58
8.6;Summary;65
8.7;Study Questions;65
8.8;Recommended Reading;66
9;Chapter 4: Measuring Behavior: Sources of Genetic and Environmental Variation;68
9.1;Overview;68
9.2;Behavioral Assays;68
9.3;Controlling Experimental Variation;72
9.4;Sources of Variation in Behavior;73
9.5;Effects of Mutations on Behavioral Phenotypes;75
9.6;Environmental Variation;77
9.7;Gene–Environment Correlation and Interaction;79
9.8;Summary;80
9.9;Study Questions;81
9.10;Recommended Reading;81
10;Chapter 5: Mapping Genotype to Phenotype in Populations;82
10.1;Overview;82
10.2;Genes in Populations: Random Mating;82
10.3;Genes in Populations: Inbreeding;83
10.4;Quantitative Genetic Model;85
10.5;Summary;93
10.6;Study Questions;93
10.7;Recommended Reading;93
11;Chapter 6: Partitioning Phenotypic Variance and Heritability;94
11.1;Overview;94
11.2;Components of Variance in Random Mating Populations;94
11.3;Genotype–Environment Correlation and Interaction;98
11.4;Partitioning Phenotypic Variance;99
11.5;Heritability: The Concept;100
11.6;Controlling and Estimating Environmental Components of Variation;102
11.7;Summary;104
11.8;Study Questions;104
11.9;Recommended Reading;105
12;Chapter 7: Estimating Heritability;106
12.1;Overview;106
12.2;Phenotypic Resemblance between Relatives;106
12.3;Genetic Causes of Covariance between Relatives;109
12.4;Environmental Causes of the Relationship between Relatives;110
12.5;Heritability Estimates in Humans;112
12.6;Heritability in Other Populations;115
12.7;Estimates of Heritability for Behavioral Traits;117
12.8;Summary;117
12.9;Study Questions;119
12.10;Recommended Reading;119
13;Chapter 8: Quantitative Trait Locus Mapping;120
13.1;Overview;120
13.2;Linkage Mapping;121
13.3;Interval Mapping;123
13.4;Statistical Analysis;123
13.5;Association Mapping;126
13.6;Quantitative Trait Locus End Game;132
13.7;Summary;135
13.8;Study Questions;136
13.9;Recommended Reading;136
14;Chapter 9: Mutagenesis and Transgenesis;138
14.1;Overview;138
14.2;The Occurrence or Induction of Mutations;138
14.3;Homologous Recombination;142
14.4;Transposon-mediated Mutagenesis;146
14.5;The GAL4-UAS Binary Expression System in Drosophila;152
14.6;RNA Interference;154
14.7;Summary;155
14.8;Study Questions;156
14.9;Recommended Reading;156
15;Chapter 10: Genomics Approaches in Behavioral Genetics;158
15.1;Overview;158
15.2;Detecting Large-scale Gene Expression;158
15.3;Parallel Sequencing and Transcriptional Analysis;163
15.4;Plasticity of Transcriptional Profiles;164
15.5;Analysis of Whole-genome Expression Microarray;165
15.6;Defining Statistical Significance Threshold;166
15.7;Identifying Genetic Networks;169
15.8;Summary;172
15.9;Study Questions;175
15.10;Recommended Reading;175
16;Chapter 11: Neurogenetics of Activity and Sleep;176
16.1;Overview;176
16.2;Locomotion;176
16.3;Genetics of Human Locomotion Disorders;179
16.4;Circadian Rhythms;182
16.5;Sleep;184
16.6;Summary;192
16.7;Study Questions;193
16.8;Recommended Reading;193
17;Chapter 12: Genetics of Social Interactions;196
17.1;Overview;196
17.2;Social Environment and the Genes–Brain–Behavior Paradigm;196
17.3;Social Cooperation and Fitness;197
17.4;Courtship and Mate Selection;197
17.5;Affiliative Behavior;204
17.6;Aggression and the Establishment of Social Hierarchies;207
17.7;Division of Labor: The Genetics of Social Structure;212
17.8;Aggregation Behavior;214
17.9;Summary;216
17.10;Study Questions;216
17.11;Recommended Reading;217
18;Chapter 13: Genetics of Olfaction and Taste;218
18.1;Overview;218
18.2;The Study of Olfaction;218
18.3;The Discovery of Odorant Receptors;218
18.4;Transgenic Approaches to Determine Odorant Receptor Response Profiles;223
18.5;Transgenic Approaches to Map Projection Patterns of Olfactory Sensory Neurons;226
18.6;The Use of Transgenic Reporter Genes to Visualize Odor Coding;227
18.7;Taste and Gustatory Receptors;235
18.8;Summary;240
18.9;Study Questions;240
18.10;Recommended Reading;241
19;Chapter 14: Learning and Memory;242
19.1;Overview;242
19.2;Forming Memories;242
19.3;Memory Formation: Cellular Mechanisms;244
19.4;Harnessing the Power of Genetics: Learning in Drosophila;247
19.5;Identifying Genetic Networks for Learning and Memory;250
19.6;Learning Disabilities;254
19.7;Neurodegeneration and Memory Impairment: Alzheimer's Disease;257
19.8;Summary;260
19.9;Study Questions;262
19.10;Recommended Reading;262
20;Chapter 15: Genetics of Addiction;264
20.1;Overview;264
20.2;Hallmarks of Addiction;264
20.3;Alcoholism;266
20.4;Linkage and Association Studies;268
20.5;Alcohol Sensitivity in Model Organisms;269
20.6;Alcohol-related Phenotypes in Rodent Models;272
20.7;Smoking;274
20.8;Drug Addiction;277
20.9;Summary;281
20.10;Study Questions;282
20.11;Recommended Reading;282
21;Chapter 16: Evolution of Behavior;284
21.1;Overview;284
21.2;Population Genetics and Evolution;284
21.3;Models of Evolution;287
21.4;Selection Models;288
21.5;Assessing Deviations from Neutrality;290
21.6;Behavior as a Vehicle for Evolution;291
21.7;Insect–Host Plant Interactions: An Example of Evolutionary Adaptation;292
21.8;Co-evolution of Sexual Communication Systems;295
21.9;The Evolutionary Genetics of Burrowing and Nest Building;299
21.10;The Astounding Diversity of Cichlids and Sticklebacks;300
21.11;Understanding the Evolution of Behavior: How Much Do We Really Know?;304
21.12;Summary;307
21.13;Study Questions;308
21.14;Recommended Reading;308
22;Glossary;310
22.1;A;310
22.2;B;312
22.3;C;313
22.4;D;315
22.5;E;316
22.6;F;317
22.7;G;318
22.8;H;319
22.9;I;320
22.10;J;321
22.11;K;321
22.12;L;321
22.13;M;322
22.14;N;323
22.15;O;324
22.16;P;325
22.17;Q;328
22.18;R;328
22.19;S;329
22.20;T;331
22.21;U;332
22.22;V;332
22.23;W;333
22.24;Z;333
23;Index;334
23.1;A;334
23.2;B;335
23.3;C;335
23.4;D;336
23.5;E;337
23.6;F;337
23.7;G;337
23.8;H;338
23.9;I;339
23.10;J;339
23.11;K;339
23.12;L;339
23.13;M;340
23.14;N;340
23.15;O;341
23.16;P;341
23.17;Q;342
23.18;R;342
23.19;S;343
23.20;T;344
23.21;U;344
23.22;V;344
23.23;W;345
23.24;Z;345
Chapter 2 Mechanisms of Neural Communication
Overview Behaviors are manifestations of the nervous system’s functions, and represent the expression of the integrated activity of neural networks in response to the animal’s perception of its external and internal environments. Although this book focuses on genetic mechanisms that predispose and enable the nervous system to manifest distinct behaviors, some knowledge of the functional organization of the nervous system is indispensable for a full appreciation of the fundamental mechanisms that direct these behaviors. In this chapter we will describe how electrical signals are elicited and propagated by neurons, and how such signals are transmitted and integrated at synapses in the nervous system. Transmission of Information in the Nervous System
The nervous system coordinates an animal’s physiology and behavior. Neurons consist of a cell body (also known as a soma or perikaryon), which contains the nucleus, mitochondria, endoplasmic reticulum, and Golgi apparatus; organelles that house the machinery for gene transcription, protein synthesis, and intermediary metabolism. Processes that emanate from the cell body are the single axon, which conducts signals away from the cell body, called efferent signals, and dendrites, which conduct signals toward the cell body, called afferent signals. The axons can extend over short or long distances, e.g. the sciatic nerve arises from the sacral region of the spinal cord to innervate the lower limbs down to the toes. Glia are supporting cells that are closely associated with neurons. Information in the nervous system is transmitted by a combination of chemical and electrical signals. How are electrical currents generated in a biological system? Electrical currents arise from movements of small numbers of ions across and along cell membranes. Since ions are charged atoms, the movement of ions will carry a current. The distribution of ions across the membrane of any cell is asymmetric, and establishes the electric field potential that drives an ion current through a conducting medium. The extracellular concentration of sodium ions (Na+) is maintained at about 145 mM, whereas its intracellular concentration is about 12 mM. Conversely, the extracellular concentration of potassium ions (K+) is only about 5 mM, whereas its intracellular concentration is about 150 mM. Most cell membranes are virtually impermeable to ions, allowing ions to leak only slowly between the cellular and extracellular fluids. This reciprocal asymmetry of Na+ and K+ concentrations is established and maintained by the ATP-dependent Na+/K+ pump (Figure 2.1). The leaking current would ultimately lead to the collapse of the Na+ and K+ gradients were it not for the Na+/K+-ATPase. This pump is electrogenic, in that it transports three sodium ions out of the cell in exchange for the entry of only two potassium ions. Inhibition of the Na+/K+-ATPase experimentally by the cardiac glycoside inhibitor ouabain causes the ion gradients to collapse, and prevents neuronal function.
Figure 2.1 The function of the Na+/K+ pump. The Na+/K+-ATPase is a tetrameric enzyme that consists of two a subunits that perform the transport of ions and two glycosylated ß subunits. Transport of three intracellular Na+ ions out of the cell, and simultaneous transport of two K+ ions into the cell, is accompanied by hydrolysis of ATP. During this process the enzyme becomes transiently phosphorylated, and the energy released by its dephosphorylation drives the exchange of monovalent ions. Electrogenic activity of the pump contributes to building up a net negative charge within the cell compared to the outside. The Resting Membrane Potential
When a cell is penetrated by an electrode containing a highly-conductive salt solution and connected to a voltage meter, a voltage, or difference in electrical potential, is measured across the membrane. This voltage is known as the membrane potential. It results primarily from the differential permeability properties of the cell membrane, but also to a small extent from the electrogenic activity of the Na+/K+ pump, and the presence of nondiffusible negatively-charged molecules inside the cell, such as nucleic acids, proteins, and negatively-charged metabolites. Thus, each cell behaves like a tiny battery: the cell’s inside is negative with regard to the outside (Figure 2.2). Let us first focus on the movement of potassium across the cell membrane. The cell membrane of neurons and glia is about twenty times more permeable to potassium than to sodium, due to the smaller hydration shell of the potassium ion, and there is thirty times less K+ outside the cell than inside. Thus, a diffusion force exists for potassium to leak out of the cell. At the same time, the charge distribution across the membrane exerts an electrochemical force that counteracts the outward diffusion of the positively-charged potassium ions. When the electrical potential exactly balances the concentration gradient driving the potassium leak, there will be no net movement of potassium, and equilibrium is established (Figure 2.3, opposite). (Note that this does not mean that there is no movement at all, but simply that the influx of potassium would equal its efflux.) Note that, at equilibrium, the membrane potential would be negative inside, not zero. Zero would be the value of the membrane potential if the ion gradients collapsed, as would be the case if the Na+/K+ pump were rendered inactive.
Figure 2.2 Diffusion forces (black arrows) and electrochemical forces (gray arrows) that act on the distribution of positively-charged ions across the cell membrane. Both the action of the Na+/K+ pump and the permeability barrier of the lipid bilayer of the membrane allow the resulting charge separation to be maintained.
Figure 2.3 Measuring current under voltage clamp in an axon. Panels A–D show current recordings following 15 mV voltage steps from -60 mV to +60 mV. Downward deflections indicate net inward currents, and upward deflections indicate net outward currents. Note that voltage steps under controlled conditions show a rapid net inward current, followed by a net outward current. In the presence of the sodium channel blocker tetrodotoxin (TTX; panel B), the inward current is abolished, whereas the net outward current still occurs. The potassium channel blocker TEA (panel D) leaves the inward current intact, but abolishes the net outward current. (Adapted from B. Hille (1984). Ionic channels of excitable membranes, Sinauer Associates, Inc., Sunderland, MA.) The equilibrium potential is defined as the theoretical voltage that would be produced across the cell membrane to counteract the tendency for ions to diffuse across it. For a single ion, e.g. K+, the equilibrium potential can be calculated using the Nernst equation, which in a simplified form is shown as: X=61/z log ([X]o[X]i) in which z is the valence of permeable ion X, and subscripts o and i refer to the concentrations of X outside and inside a cell at 37°C. Since the intracellular and extracellular concentrations of potassium are known, we can calculate that the membrane potential at equilibrium would be about -90 mV, if potassium were the only ion able to move across the membrane (the minus sign indicates that the inside of the cell would be negative with respect to the outside). This is called the equilibrium potential for potassium, abbreviated to EK. Similarly, if sodium were the only ion to diffuse across the cell membrane, it would generate an equilibrium potential for sodium, i.e. ENa, of about +60 mV under physiological conditions. The Nernst equation is important, in that it allows calculation of the membrane potential expected for diffusion of a single ion when the concentrations on both sides of the membrane are known. Since potassium is not the only ion to which the cell membrane is permeable, the empirically measured membrane potential is weighted among the equilibrium potentials of all ions that can move across the membrane. This is known as the resting membrane potential. In mammalian neurons and glial cells it is approximately -70 mV. This value is closer to EK than to ENa, because the membrane is more permeant to potassium than to sodium. Note that only a very small fraction of the cellular sodium needs to move to establish a relatively large difference in electrical potential. The resting membrane potential can be estimated using the Goldman-Hodgkin-Katz equation, which is an extension of the Nernst equation to include all permeable monovalent ions: =RT/zFln ?? (PNa[Na]o+PK[K]o+PCl[Cl]iPNa[Na]i+PK[K]i+PCl[Cl]o) where E is the membrane potential at equilibrium, R is the gas constant (8.314 V C K-1 mol-1 in electrical units), T the temperature in °K, z is the valence of the permeantion, F is Faraday’s constant (9.648 × 104 C mol-1), and P is the permeability of the membrane to the ion indicated in the subscript. If the membrane permeability were to be changed by opening...
