The Neurobiology of Brain and Behavioral Development

Robbin Gibb, Bryan Kolb, Robbin Gibb, Bryan Kolb

• Publisher: Academic Press
• Year: 2017
• ISBN:
  9780128040843
• Topic: Psicología
• Subtopic: Neuropsicología

The Neurobiology of Brain and Behavioral Development provides an overview of the process of brain development, including recent discoveries on how the brain develops. This book collates and integrates these findings, weaving the latest information with core information on the neurobiology of brain development. It focuses on cortical development, but also features discussions on how the other parts of the brain wire into the developing cerebral cortex. A systems approach is used to describe the anatomical underpinnings of behavioral development, connecting anatomical and molecular features of brain development with behavioral development.The disruptors of typical brain development are discussed in appropriate sections, as is the science of epigenetics that presents a novel and instructive approach on how experiences, both individual and intergenerational, can alter features of brain development. What distinguishes this book from others in the field is its focus on both molecular mechanisms and behavioral outcomes. This body of knowledge contributes to our understanding of the fundamentals of brain plasticity and metaplasticity, both of which are also showcased in this book.

• Provides an up-to-date overview of the process of brain development that is suitable for use as a university textbook at an early graduate or senior undergraduate level
• Breadth from molecular level (Chapters 5-7) to the behavioral/cognitive level (Chapters 8-12), beginning with Chapters 1-4 providing a historical context of the ideas
• Integrates the neurobiology of brain development and behavior, promoting the idea that animal models inform human development
• Presents an emphasis on the role of epigenetics and brain plasticity in brain development and behavior

Part I

General Perspectives in Brain Development

Outline

Chapter 1 Brain Development

Chapter 2 Perspectives on Behavioral Development

Chapter 3 Overview of Factors Influencing Brain Development

Chapter 4 The Role of Animal Models in Developmental Brain Research

Chapter 1

Brain Development

Robbin Gibb and Anna Kovalchuk, University of Lethbridge, Lethbridge, AB, Canada

Abstract

The human brain has been described as the most complicated biological object in existence. Yet the brain is the substrate for sophisticated human behavior, so perhaps it’s complexity is predictable. The development of the brain follows a genetic blueprint and this blueprint organizes basic structures and connections in the brain. But brain development is also sensitive to the environment. An individual’s experiences can dictate connections to be dismantled or retained in the wiring circuitry of the brain. Two main cell types, neurons and glia, comprise the brain and they appear in various forms at different phases of brain development. In maturity, the brain has approximately 86 billion neurons and about the same number of glial cells. The process of transforming the embryonic neural plate to the exquisitely complex and fully developed brain, is the topic of discussion in this chapter.

Keywords

Neurogenesis; synaptogenesis; cell migration; differentiation; myelination; epigenetic; synaptic pruning; apoptosis; neurotransmitters; neural plasticity

Abbreviations

bRGC basal radial glia cell

CR Cajal Retzius

CNS central nervous system

Cl⁻ chloride

E embryonic

GABA γ-aminobutyric acid

ICI inhibitory cortical interneuron

IPC intermediate precursor cell

Na⁺ sodium

NEC neuroepithelial cell

OPC oligodendrocyte progenitor cell

RGC radial glial cell

RMS rostral migratory stream

SNP short neural precursor

SVZ subventricular zone

VZ ventricular zone

1.1 Introduction

Human brain development is a protracted process that begins soon after conception and continues at least into the third decade of life. The brain is crafted by the lifelong interplay of generative (cell birth and synapse formation) and degenerative processes (cell death and synaptic pruning), which are modulated to varying degrees by an individual’s experiences. The process of brain development is programed by information encoded on DNA, a double-helical molecule that provides a genetic blueprint for construction. Genes, key units of inheritance, are said to be expressed—turned on or off, giving rise to gene products—proteins that influence the function of the brain and the cells that comprise it. Genes are expressed in an organized and intricately controlled manner, governing the proper and structured step-wise development and maturation of cells and brain areas. The control of gene expression is regulated through epigenetic (above-genetic) phenomena—methylation of DNA, modifications of histone proteins and chromatin remodeling, and noncoding RNA-mediated effects. (For a detailed discussion of epigenetics see Chapter 7: Epigenetics and Genetics of Brain Development.) Epigenetic changes are flexible and reversible, and are influenced by physical, chemical, biological and social environmental factors, and life experiences. Epigenetic changes are also heritable and therefore might carry an imprint of exposures and experiences of previous generations. Although the process of brain development is fundamentally the same for each individual, environmental exposures can alter the way in which the developmental program manifests. This environmental modulation of genetic expression is called epigenetic programing and its effects can be seen in the preconception period (e.g., Mychasiuk, Harker, Ilnytskyy, & Gibb, 2013), the prenatal period (e.g., Mychasiuk et al., 2012), and through the lifespan of the individual (e.g., Harker et al., 2015). Mounting evidence demonstrates that the experiences of our forbearers can and often do result in epigenetic changes in gene expression ultimately changing the expression of proteins. Because proteins are the building blocks of the brain, different proteins build different brains by modifying cell number, cell connectivity, brain size, and ultimately, behavior. Epigenetic programing thus provides an adaptive means for an organism to prepare its brain for the unique environmental challenges that it will face without changing its genetic blueprint. Our experiences and the experiences of our predecessors are able to turn certain genes “on” or “off” as per specific mechanisms of epigenetic regulation, thus regulating brain development and function (Fig. 1.1).

Figure 1.1 Epigenetic mechanisms. The blue circles represent methyl groups for the DNA methylation and histone modification figures. In the case of RNA modification, the blue circle represents a non-coding RNA bound to the mRNA (After Kolb & Whishaw, 2014).

1.2 Cells of the Brain

The brain is composed of two main classes of cells: neurons and glia. Neurons are electrically active cells that form connections with other neurons (synapses) and communicate in a systematic fashion to produce behavior. Neurons have a cell body, dendrites and an axon. The dendrites receive incoming information from other connected cells. The cell body is the control center of the cell and it integrates the information it receives. An electrochemical (neurotransmitter) response is then transmitted along the axon to cells connected further down the line. Neurons can be classified as one of two fundamental types: excitatory projection neurons and inhibitory interneurons. Excitatory cells typically bear dendritic spines, protrusions on the dendrite, which form at sites of synaptic contact. They can be of a pyramidal or stellate (star-shaped) form. Inhibitory interneurons do not have spines and usually appear in a stellate form Fig. 1.2.

Figure 1.2 Neural cell types.

Glial cells are cells that support neural function. They are smaller than neurons and lack both dendrites and axons. The name glia derives from the Greek word meaning glue. It was originally proposed that these cells were responsible for holding the brain together, yet no evidence exists for any glue-like or binding function. Despite our long-held view that glial cells are “helper cells” for neurons, current evidence points to a much larger role for these cells in modulation and maintenance of neural function. In addition, glia are involved in processes of reuptake of neurotransmitters, providing a structural scaffolding for neural migration, and supporting recovery after brain injury.

1.2.1 Neural cells

All cells in the mature brain arise from the precursor neuroepitheal cells that are expressed during development. Once in their end stage of development neural cells fall into one of two principal cell classes.

Excititory projection neurons are spiny and typically communicate with other cells by use of the neurotransmitter glutamate. Inhibitory interneurons are smooth and use γ-aminobutyric acid (GABA) as their neurotransmitter (Fig. 1.2).

1.2.2 Glial cells

Mature glial cells can be classified as either macroglia or microglia. This distinction of glial subtypes arises not only on the basis of their size but also by their site of origin. Macroglia are derived from the neuroectodermal layer of the embryo whereas microglia originate in the mesodermal layer.

1.2.2.1 Macroglia

There are three main types of macroglia: astrocytes, oligodendrocytes, and ependymal cells.

Astrocytes are the most plentiful form of macroglia. Their roles include regulation of neuron production, maintainence of neural networks, and modulation of neural activity and communication (Jernigan & Stiles, 2017). Oligodendrocytes are cells that produce myelin in the central nervous system (CNS). Myelin is a fatty substance that insulates axonal fibers, thereby enhancing the speed of neural transmission.

Ependymal cells are found in the ventricular walls of the brain and in conjunction with local capillary beds comprise the choroid plexus. The choroid plexus produces the cerebrospinal fluid that fills the ventricular system providing a cushion that serves to protect the brain.

1.2.2.2 Microglia

Microglia have been traditionally considered the sole provider of immune support to an immunodeficient Brain. They are known to monitor for signs of infection, clear debris, and support the inflammation and Repair response to brain injury and disease. New research has expanded the role of microglia to include cell proliferation, synaptic pruning, and sex-specific changes in brain development (Shafer & Stevens, 2015: see Chapter 14: Hormones and Development for a more detailed discussion).

1.3 Phases of Brain Development

Genetically preset, the process of brain construction occurs in seven well-defined phases that extend over a prolonged period of brain development (Kolb & Whishaw, 2014). Some phases are more or less confined to restricted periods whereas others are in play for extended periods of time (Table 1.1).

Table 1.1

Seven phases of brain development

Developmental phase	Process
1. Cell birth	Genesis of neurons and glia
2. Cell migration	Movement of cells to their functional position
3. Cell differentiation	Precursors cells transform to specified cell type
4. Cell maturation	Growth of dendrites and axons
5. Synaptogenesis	Formation of cell to cell communication sites – synapses
6. Cell death and synaptic pruning	Programed cell death and dismantling of unused circuitry
7. Myelination	Formation of myelin sheath to enhance speed of neurotransmission

Each phase will be considered in depth in the developmental period(s) during which it predominately occurs and unless otherwise specified should be considered typical of human development.

1.4 Constructing the Human Brain

1.4.1 Construction of the brain: embryonic development (conception to week 8)

By embryonic day 13 (E17), the process of replacing the single layer blastula with a trilayer structure known as the gastrula begins. By the end of gastrulation (E20) the endodermal, mesodermal, and ectodermal layers of the trilamina have formed. The ectodermal layer gives rise to both the skin and the CNS. Importantly, the neuroepithelial cells (NECs), which eventually produce cells that make the neurons and glia are found within this layer. The neural plate forms on E21 and by E22 the neural groove becomes apparent. The neural groove fuses starting on E23 to form the neural tube (neurulation) with the central section closing first. The rostral portion of the neural tube is inhabited by the earliest migrating cells and becomes the brain while the caudal portion receives later migrating cells and forms the spinal cord (Stiles & Jernigan, 2010). The rostral and caudal regions of the neural tube are the last to close.

Neural tube defects are birth defects that affect the brain or spinal cord. Failure of the rostral section of the neural tube to close on E23–E26 results in a condition known as anencephaly where the brain and skull fail to fully develop. Infants born with anencephaly usually lack sensory processing abilities and are unable to feel pain. They generally die soon after birth. Spina bifida is the result of incomplete closure of a portion of the caudal end of the neural tube on about E28. The symptoms of spina bifida range in severity but it is most commonly characterized by paralysis of the legs. Both anencephaly and spina bifida often result from a lack of the B vitamin, folate, in the diet.

The cylindrical cavity in the neural tube eventually becomes the ventricular system and the NECs inhabit this region, also known as the ventricular zone (VZ) (Phase 1—cell birth). The NECs are aligned in the VZ in an apico-basilar fashion. At the ventricular (apical) surface the NECs are bound together by both tight and adherens junctions which provide important adhesive contact between neighboring cells. Adherins junctions mediate the maturation and maintenance of the contact while tight junctions regulate the transport of ions and other molecules between the cells (Hartsock & Nelson, 2008). At the p...