The Cerebral Cortex in Neurodegenerative and Neuropsychiatric Disorders

Experimental Approaches to Clinical Issues

David F. Cechetto, Nina Weishaupt

• Publisher: Academic Press
• Year: 2016
• Print ISBN: 9780128019429
• eBook ISBN: 9780128019566
• Topic: Medicine
• Subtopic: Neurology

The Cerebral Cortex in Neurodegenerative and Neuropsychiatric Disorders: Experimental Approaches to Clinical Issues focuses on how pre-clinical investigations are addressing the clinical issues surrounding the involvement of the cerebral cortex in selected conditions of the nervous system, including Alzheimer's Disease, Parkinson's, addiction, and cardiovascular dysregulation. Each chapter is written by an expert in his/her field who provides a comprehensive review of the clinical manifestations of cortical involvement and experimental techniques currently available to tackle cortical issues in disease. Thus, this present title provides a link between cortical clinical problems and investigational approaches to help foster future research with high translational value. - Offers a comprehensive overview on the best available in vivo and in vitro models to study cortical involvement - Presents models and specific techniques that help to guide investigators in their choices on how to address research questions experimentally - Provides expert commentary and a perspective on future trends at the end of each chapter - Addresses translational advances and promising therapeutic options - Includes references to key articles for additional detailed study

Part I

Introductory Chapters

Outline

Chapter 1. Anatomy of the Cerebral Cortex

Chapter 2. Cortical Plasticity in Response to Injury and Disease

Chapter 3. Imaging Approaches to Cerebral Cortex Pathology

Chapter 1

Anatomy of the Cerebral Cortex

K.S. Rockland Boston University School of Medicine, Boston, MA, United States

Abstract

The neocortex in rodents and primates exhibits several common properties; namely, areas, layers, columns, cell types, and connections. These properties are briefly reviewed here, with the goal of providing orientation and general background for the following chapters on experimental approaches to neurodegenerative and neuropsychiatric disorders. Special attention is given to primate and rodent homologies but also to species specializations. Because cortical anatomy, despite over 100 years of research, remains poorly understood, this chapter also aims to convey some appreciation of open questions and controversies.

Keywords

Areas; Columns; Connections; Homologies; Interneurons; Layers; Minicolumns; Neurochemistry; Pyramidal neurons

Introduction

The distinctive core features of neocortical anatomy were already recognized by the early architectonic investigators; namely, layers, verticality, and regional differences in cellular and myelin distribution, defined as discrete areas. In the 100 years or so since the first maps of the Vogts and Brodmann, cortical research has forged ahead, especially in terms of cell types, intraareal and interareal connectivity, and, most recently, gene expression. Needless to say, given the complexity of brain structure and function, the overall cortical organization is at best only partially understood, and almost every feature (layers, cell types, verticality or “columns,” and areas) remains under active investigation and debate. As just one example, a popular proposal of cortical uniformity (Rockel, Hiorns, & Powell, 1980) has been replaced, after the introduction of different counting techniques, by new data more supportive of systematic, cross-cortex and cross-species variation (Charvet, Cahalane, & Finlay, 2015; DeFelipe, Alonso-Nanclares, & Arellano, 2002).

The present chapter, while keeping in mind the open questions on cortical anatomy, aims to provide general orientation and background. Given the prominence of animal models in experimental approaches to disease, special attention is given to differences between human and rodent cortical anatomy. Finer species specializations are not considered, although these are increasingly attracting attention (in rodents, eg, Beaudin, Singh, Agster, & Burwell, 2013; Krubitzer, Campi, & Cooke, 2011). Some of the obvious specializations are briefly discussed in this introductory section, followed by more extensive discussion of areas, layers, verticality, cell types, and connections. A substantial body of longer reviews and chapters is available for further detail (eg, Douglas, Markram, & Martin, 2004; Kirkcaldie, 2012; Zilles, 2004, Chapter 27; Zilles & Wree, 1995).

An obvious distinction of the cerebral cortex in humans is the expansion, considered as a hallmark of human evolution. The human cortex is thicker, has more cells than the smaller brains of rats and mice, and has more areas. It has more white matter, in contrast with rodents, where connections often travel through the deeper cortical layers and not through the relatively shallow white matter. The human brain is gyrencephalic (ie, highly folded), albeit not uniquely so, because this property is shared with other species such as cats, dogs, nonhuman primates, and the large-brained elephant and cetaceans.

Gyrencephaly, whether in human or other large brains, has important consequences for differential architectonics and connectivity (Mota & Herculano-Houzel, 2012; Sun & Hevner, 2014). The laminar thickness and spatial arrangement are altered at the gyral crown, sulcal walls, and sulcal depths. The sulcal depths are preferentially associated with the short-distance U-fiber connections. Several causal mechanisms have been proposed for cortical folding (Zilles, Palomero-Gallagher, & Amunts, 2013), including an important role for the proliferative cycle in early development. Current ideas raise the possibility that gyrencephaly should be accepted as the ancestral mammalian trait (Lewitus, Kelava, Kalinka, Tomancak, & Huttner, 2014).

Hemispheric laterality, both functional and anatomical, is a pronounced feature of the human neocortex, although laterality effects have been reported in other species; for example, in aquatic mammals, unihemispheric sleep and hemispheric independence of eye movements (Mortensen et al., 2014). Hippocampal asymmetry in a long-term memory task has been reported in mice (Shipton et al., 2014).

With few exceptions, the same neuron types are found in primates and rodents, although there are differences in degree of dendritic branching and density of dendritic spines (Ballesteros-Yanez, Benavides-Piccione, Elston, Yuste, & DeFelipe, 2006; Benavides-Piccione, Ballesteros-Yanez, DeFelipe, & Yuste, 2002; Elston, Benavides-Piccione, Elston, Manger, & DeFelipe, 2011). Area distribution is variable, especially of interneurons (DeFelipe, Gonzalez-Albo, Del Rio, & Elston, 1999, DeFelipe, Ballesteros-Yanez, Inda, & Munoz (2006); Roux & Buzsaki, 2015). Narrow spindle cells (ie, Von Economo cells) are not found in rodents but do occur in other species besides humans (Butti, Santos, Uppal, & Hof, 2013; Evrard, Forro, & Logothetis, 2012; Seeley et al., 2012). Similarly, giant cells in the motor or visual cortex do not occur in rodents but do occur in other species besides humans. Astrocytes are disproportionately larger in humans than in mice, and their processes are more complex (Oberheim, Wang, Goldman, & Nedergaard, 2006).

An important difference between primates and rodents relates to the thalamus and, by extension, to the organization of thalamocortical connections. With the exception of the visual thalamus, there are significantly fewer inhibitory neurons in the rodent thalamus (Jones, 2010), and the reticular nucleus of the thalamus, composed of inhibitory neurons, is enlarged. The extent and density of axons immunoreactive (denoted by the suffix-ir) for the dopamine transporter (DAT) is remarkably greater in the macaque dorsal thalamus (and, by extension, presumably in humans), with the mediodorsal association nucleus and the ventral motor nuclei having the densest immunolabeling (Fig. 1.1). Ultrastructural analysis of the macaque mediodorsal nucleus reveals that thalamic interneurons (which are absent in the rodent) are a main postsynaptic target of DAT-ir axons (Garcia-Cabezas, Martinez-Sanchez, Sanchez-Gonzalez, Garzon, & Cavada, 2009).

Figure 1.1 Distribution of dopamine transporter immunoreceptive (DAT-ir) axons (red) in parasagittal sections of the rat (A–D) and macaque monkey thalamus (E, F). Note differential distribution and greater density in the macaque thalamus. Reproduced with permission from Oxford University Press, Garcia-Cabezas et al., (2009). Dopamine innervation in the thalamus: monkey vs rat. Cerebral cortex 19 (2), 424–434.

Almost as notable as species differences are the many conserved features of cortical organization between primates and rodents. The primary cortical areas are recognizable across species, as are the basic cortical layers and cell types, and the main neurochemical transmitter and neuromodulatory systems. Despite the previously mentioned differences in thalamic organization, both primates and rodents have a conspicuous parallel system of driving corticothalamic projections from layer 5 and modulatory corticothalamic projections from layer 6 (Rouiller & Welker, 2000).

Cortical Areas

In the general mammalian plan, the cerebral cortex is parcellated into discrete motor, primary sensory, and association areas (Zilles, 2004, Chapter 27). The number of cortical areas, exclusive of the primary sensory and motor areas, is species-dependent. Individual areas are specified by the interplay o...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Foreword
• Introduction
• Part I. Introductory Chapters
• Part II. The Cerebral Cortex in Neurodegenerative Disorders
• Part III. The Cerebral Cortex in Neuropsychiatric Disorders
• List of Acronyms and Abbreviations
• Index