Principles of Neurobiology

Liqun Luo

• Publisher: Garland Science
• Year: 2020
• ISBN:
  9781000096866
• Topic: Biological Sciences
• Subtopic: Neuroscience
• Edition: 2

Principles of Neurobiology, Second Edition presents the major concepts of neuroscience with an emphasis on how we know what we know. The text is organized around a series of key experiments to illustrate how scientific progress is made and helps upper-level undergraduate and graduate students discover the relevant primary literature. Written by a single author in a clear and consistent writing style, each topic builds in complexity from electrophysiology to molecular genetics to systems level in a highly integrative approach. Students can fully engage with the content via thematically linked chapters and will be able to read the book in its entirety in a semester-long course. Principles of Neurobiology is accompanied by a rich package of online student and instructor resources including animations, figures in PowerPoint, and a Question Bank for adopting instructors.

CHAPTER 1
An Invitation to Neurobiology

The brain is a world consisting of a number of unexplored continents and great stretches of unknown territory.

Santiago Ramón y Cajal

How does the nervous system control behavior? How do we sense the environment? How does the brain create a representation of the world out of the sensations? How much of our brain function and behavior is shaped by our genes, and how much reflects the environment in which we grew up? How is the brain wired up during development? What changes occur in the brain when we learn something new? How have nervous systems evolved? What goes wrong in brain disorders?

We are about to embark on a journey to explore these questions, which have fascinated humanity for thousands of years. Our ability to address these questions experimentally has greatly expanded in recent years. What we currently know about the answers to these questions comes mostly from findings made in the past 50 years; in the next 50 years, we will likely learn more about the brain and its control of behavior than in all of prior human history. We are at an exciting time as students of neurobiology, and it is my hope that many readers of this book will be at the forefront of groundbreaking discoveries.

PRELUDE: NATURE AND NURTURE IN BRAIN FUNCTION AND BEHAVIOR

As we begin this journey, let’s discuss one of the questions we raised regarding the contributions of genes and environment to our brain function and behavior. We know from experience that both genetic inheritance (nature) and environmental factors (nurture) make important contributions, but how much does each contribute? How do we begin to tackle such a complex question? In scientific research, asking the right questions is often a critical step toward obtaining the right answers. As evolutionary geneticist Theodosius Dobzhansky put it, “The question about the roles of the genotype and the environment in human development must be posed thus: To what extent are the differences observed among people conditioned by the differences of their genotypes and by the differences between the environments in which people were born, grew and were brought up?”

1.1 Human twin studies can reveal the contributions of nature and nurture

Francis Galton first coined the phrase nature versus nurture in the nineteenth century. He also introduced a powerful method for studying this conundrum: statistical analysis of human twins. Identical twins (Figure 1-1), or monozygotic twins, share 100% of their genes in almost all cells, as they are products of the same fertilized egg, or zygote. One can compare specific traits among thousands of pairs of identical twins to see how correlated they are within each pair. For example, if we compare the intelligence quotients (IQs)—an estimate of general intelligence—of any two random people in the population, the correlation is 0. (Correlation is a statistic of resemblance that ranges from 0, indicating no resemblance, to 1, indicating perfect resemblance.) This correlation is 0.86 for identical twins (Figure 1-2), a striking similarity. However, identical twins also usually grow up in the same environment, so this correlation alone does not help us distinguish between the contributions of genes and the environment.

Figure 1-1 Identical (monozygotic) twins. Identical twins develop from a single fertilized egg and therefore share 100% of their genes in almost all cells (some lymphocytes are an exception due to stochasticity in DNA recombination). Most identical twins also share similar childhood environments. (Courtesy of Christopher J. Potter.)

Figure 1-2 Twin studies for determining genetic and environmental contributions to intelligence quotient (IQ). (A) Correlation, or R value, of IQ scores for 4672 pairs of monozygotic twins and 5546 pairs of dizygotic twins. The correlation between the IQ scores of randomly selected pairs of individuals is zero. The difference in correlation between monozygotic and dizygotic twins can be used to calculate the heritability of traits. The large sample size makes these estimates highly accurate. (B) Simulation of IQ score correlation plots for 5000 pairs of unrelated individuals (R = 0), 5000 pairs of dizygotic twins (R = 0.60), and 5000 pairs of monozygotic twins (R = 0.86). The x and y axes of a given dot represent the IQ scores of one pair. The simulations assume a normal distribution of IQ scores (mean = 100, standard deviation = 15). (A, based on Bouchard TJ & McGue M [1981] Science 212:1055–1059.)

Fortunately, human populations provide a second group that allows researchers to tease apart the influence of genetic and environmental factors. Nonidentical (fraternal) twins occur more often than identical twins in most human populations. These are called dizygotic twins because they originate from two independent eggs fertilized by two independent sperm. As full siblings, dizygotic twins are 50% identical in their genes according to Mendel’s laws of inheritance. However, like monozygotic twins, dizygotic twins usually share very similar prenatal and postnatal environments. Thus, the differences between traits exhibited by monozygotic and dizygotic twins should result from the differences in 50% of their genes. In our example, the correlation of IQ scores between dizygotic twins is 0.60 (Figure 1-2).

Behavioral geneticists use the term heritability to describe the contribution of genetic differences to trait differences. Heritability is defined as the difference between the correlations of monozygotic and dizygotic twins multiplied by 2 (because the genetic difference is 50% between monozygotic and dizygotic twins). Thus, the heritability of IQ is (0.86 − 0.60) × 2 = 0.52. Roughly speaking, then, genetic differences account for about half of the variation in IQ scores within human populations. Traditionally, the non-nature component has been presumed to come from environmental factors. However, “environmental factors” as calculated in twin studies include all factors not inherited from the parents’ DNA. These include the postnatal environment, which is what we typically think of as nurture, but also prenatal environment, stochasticity in developmental processes, somatic mutations (alterations in DNA sequences in somatic cells after fertilization), and gene expression changes due to epigenetic modifications. Epigenetic modifications refer to changes made to DNA and chromatin that do not modify DNA sequences but can alter gene expression—these include DNA methylation and various modifications of histones, the protein component of chromatin. As we will learn later, all of these factors contribute to nervous system development, function, and behavior.

Twin studies have been used to estimate the heritability of many human traits, ranging from height (~90%) to the chance of developing schizophrenia (60–80%). An important caveat regarding these estimates is that most human traits result from complex interactions between genes and the environment, and heritability itself can change with the environment. Still, twin studies offer valuable insights into the relative contributions of genes and nongenetic factors to many aspects of brain function and dysfunction in a given environment. The completion of the Human Genome Project and the development of tools permitting detailed examination of the genome sequence data, combined with a long history of medical and psychological studies of human subjects, have made our own species the subject of a growing body of neurobiological research (Section 14.5). However, mechanistic understanding of how genes and the environment influence brain development, function, and behavior requires experimental manipulations that often can be carried out only in animal models. The use of vertebrate and invertebrate model species (Sections 14.1–14.4) has yielded much of what we have learned about the brain and behavior. Many principles of neurobiology revealed by experiments on specific model species have turned out to operate in a wide variety of organisms, including humans.

1.2 Examples of nature: animals exhibit instinctive behaviors

Animals exhibit remarkable instinctive behaviors that help them find food, avoid danger, seek mates, and nurture their progeny. For example, a baby penguin, directed by its food-seeking instinct, bumps its beak against its parent’s beak to remind its parent to feed it; in response, the parent instinctively releases the food it has foraged from the sea to feed its baby (Figure 1-3).

Figure 1-3 Penguin feeding. The instinctive behaviors of an adult penguin and its offspring photographed in Antarctica, 2009. Top, the young penguin asks for food by bumping its beak against its parent’s beak. Bottom, the parent releases the food into the young penguin’s mouth. (Courtesy of Lubert Stryer.)

Instinctive behaviors can be elicited by very specific sensory stimuli. For instance, experimenters have tested the responses of young chicks to an object resembling a bird in flight, with wings placed close to either end of the head–tail axis. When moved in one direction, the object looks like a short-necked, long-tailed hawk; when moved in the other direction, the object looks like a long-necked, short-tailed goose. Seeing the object overhead, a young chick produces different responses depending on the direction in which the object moves, running away when the object resembles a hawk but making no effort to escape when t...