Axons and Brain Architecture

Kathleen Rockland

• Publisher: Academic Press
• Year: 2015
• Print ISBN: 9780128013939
• eBook ISBN: 9780128016824
• Topic: Biological Sciences
• Subtopic: Neuroscience
• Index: Biological Sciences

Several excellent monographs exist which deal with axons. These, however, focus either on the cellular and molecular biology of axons proper or on network organization of connections, the latter with only an incidental or abstract reference to axons per se. Still relatively neglected, however, is the middle ground of terminations and trajectories of single axons in the mammalian central nervous system. This middle level of connectivity, between networks on the one hand and local, in vitro investigations on the other, is to some extent represented by retrograde tracer studies and labeled neurons, but there have so far been many fewer of the complementary anterograde studies, with total visualization of the axonal arborization.The present volume brings together in one source an interrelated treatment of single axons from the perspective of microcircuitry and as substrates of larger scale organization (tractography). Especially for the former area - axons in microcircuitry - an abundance of published data exists, but these are typically in specialty journals that are not often accessed by the broader community. By highlighting and unifying the span from microcircuitry to tractography, the proposed volume serves as a convenient reference source and in addition inspires further interactions between what currently tend to be separate communities. The volume also redresses the imbalance between in vitro/local connectivity and long-distance connections.Focusing on mammalian systems, Part 1 of this book is devoted to anatomical investigations of connections at the single axon level, drawing on modern techniques and classical methods from the 1990s. A particular emphasis is on broad coverage of cortical and subcortical connections from different species, so that common patterns of divergence, convergence, and collateralization can be easily appreciated. Part 2 addresses mechanisms of axon guidance, as these seem particularly relevant to pathways and branching patterns. Part 3 covers axon dynamics and functional aspects; and Part 4 focuses on tractography, notably including comparisons between histological substrates and imaging.- A novel innovative reference on the axon as a connectional unit, encompassing microcircuitry, axon guidance, and function- Featuring chapters from leading researchers in the field- Full-colour text that includes both an overview of axon function and the multiple underlying molecular mechanisms- The only volume to bring together the configuration of individual axons at a circuit level and to relate the histological geometry of axons and axon bundles to in vivo tractography imaging studies

Section I

Microcircuitry

Outline

Section I. Microcircuitry

Chapter 1 Axonal Projection of Olfactory Bulb Tufted and Mitral Cells to Olfactory Cortex

Chapter 2 The Primate Basal Ganglia Connectome As Revealed By Single-Axon Tracing

Chapter 3 Comparative Analysis of the Axonal Collateralization Patterns of Basal Ganglia Output Nuclei in the Rat

Chapter 4 Anatomy and Development of Multispecific Thalamocortical Axons: Implications for Cortical Dynamics and Evolution

Chapter 5 Geometrical Structure of Single Axons of Visual Corticocortical Connections in the Mouse

Chapter 6 Interareal Connections of the Macaque Cortex: How Neocortex Talks to Itself

Chapter 7 Topography of Excitatory Cortico-cortical Connections in Three Main Tiers of the Visual Cortex: Functional Implications of the Patchy Horizontal Network

Chapter 8 Do Lateral Intrinsic and Callosal Axons Have Comparable Actions in Early Visual Areas?

Chapter 9 Neuronal Cell Types in the Neocortex

Chapter 10 Anterograde Viral Tracer Methods

Section I. Microcircuitry

Overview

Individual axons in their distal, terminal portions have been extensively investigated as presynaptic components of circuits within their various target structures. In their full entirety, including local collaterals and potentially multiple branches, they participate in broader networks; that is, the anatomical substrate of brain organization. Ideally, we want to visualize the totality of an axon (its parent neuron, arbors and terminations, and postsynaptic neurons) in space and time, to learn how the distributed information is used and coordinated in various behaviors. At the network level, however, relatively little information is available about the function and even the overall light microscopic configuration of axons in their entirety.

The first four chapters in this section review axon phenotypes in three different systems; namely, olfactory, basal ganglia, and thalamocortical (TC). In Chapter 1, Kensaku Mori discusses the strikingly different phenotypes of the two major olfactory projection neurons; namely, spatially focal projections of tufted cells and spatially dispersed projections of mitral cells. In this relatively well-studied system, the two phenotypes can be tightly and differentially associated with the inhalation–exhalation respiratory cycle, and are shown to have distinct but complementary spatiotemporal roles.

The next two chapters, by Martin and Andre Parent and by Elisa Mengual and colleagues, elaborate on axonal configurations within the several target structures of the basal ganglia. Notably, fine analysis shows morphological variability within each of the major outputs, in terms of whether neurons terminate in one area alone or branch to several. As remarked by both research groups, the diversity can be taken as a sign of exquisitely precise interactions in the context of complex spatiotemporal sequences across the interconnected network.

In Chapter 4, Francisco Clasca and colleagues present evidence for a substantial revision of the traditional distinction between topographically precise, area-specific TC axons versus divergent TC axons that had been thought to diffusely target the superficial layers of many areas. They demonstrate “multispecific” TC axons that branch in defined patterns to separate cortical areas. From this, a novel architecture emerges, with implications for the dynamics, plasticity, and evolution of TC-based networks.

The chapter by Denis Boire and colleagues focuses on corticocortical axons in the mouse. They demonstrate that projection foci, when dissected to the level of the contributing axons, are averages of highly diversified individual axons, presumably each with different integration properties. From this, the authors stress that a single cortical connection is not a single functional channel. Further implications for computational structure, connectional strengths (the distinction of “driving” vs. “modulatory”), and hierarchical organization are considered.

Issues of brain architecture continue as a theme in the chapter by John Anderson and Kevan Martin, where the authors review an extensive body of work on corticocortical axons and interrogate established ideas on cortical organization (Serial Processing and Lateral thinking). They consider what synaptic data can tell us about design principles of cortical connections and the interactions of local and long-distance connections. As in previous chapters, these authors also return to the issue of diversity: “What has been lost in these generalizations, however, is the variance [within] the projections…. This variance is instantly clear from the composite LM drawing shown in Fig. 2….”

The relation between single axons and populational patterns is further treated in Chapters 7 (Zoltan Kisvarday) and 8 (Kerstin Schmidt). Both authors focus on the still mysterious system of patchy intrinsic connections. This system corresponds to local, intraareal collaterals and terminations of pyramidal neurons. These local collaterals are a general cortical feature, except that the patchiness is not apparent in rodents. The patches are approximately the same size and spacing as functional domains in visual cortex; and both Kisvarday and Schmidt review the extensive work to spatially coregister anatomical patches with core visual features such as orientation selectivity. As they both point out, the relationship is biased but not absolute, raising questions as to the complexity of anatomical mechanisms underlying feature selectivity: there is evidence for both iso- and cross-orientation connectivity. Results are further discussed in relation to perceptual processes, physiological response properties in visual circuits, and several different functional models. Kerstin Schmidt also proposes a close functional and anatomical association of the lateral intrinsic system and callosal connections, and discusses the comparable actions on physiological responses.

Issues of functional organization are also developed in Chapter 9 by Oberlaender and colleagues working on mouse barrel cortex. This chapter is representative of hybrid experimental-statistical, probabilistic approaches (reverse engineering) to connectivity that aim toward incorporating quantitative data into a dense cortex model for predicting local and long-range synaptic inputs. Using an interactive software environment called NeuroNet, the authors group cortical neurons into 10 basic excitatory types that share common morphological and physiological properties; in particular, somadendritic morphology, TC innervation, ongoing/sensory-evoked spiking, and inter- and intralaminar intrinsic axonal projections.

Finally, in Chapter 10, Kevin Beier presents a summary of tracing techniques, with a particular emphasis on the newer virus-based methods. Low-titre Sindbis virus, for example, is fast becoming an alternative to juxtacellular labeling, at least in rodents.¹ Special mention is also given to the emerging transsynaptic methods, which offer great promise for mapping out interconnected sets of neurons. Beyond their use in tracing experiments, viral vectors enable activity-related manipulations (i.e., optogenetics); and as fluorescent tags, they enable whole-brain axon tracing, a promising alternative to traditional, stacked reconstructions from two-dimensional histology slices.

In summary, this Section presents several examples of whole axon configurations. Main points are that (i) these differ significantly and to some extent are “fingerprint” recognizable for specific projections; (ii) within a single projection, there are typically a range of different axon morphologies; (iii) the relation to functional architectures (such as orientation selectivity) is not straightforward and may recruit multiple mechanisms. Single axon analysis, as the reader will appreciate, superbly reveals divergence within a target and across targets. In some cases, as for the olfactory projections, axonal configurations can be associated with a relatively detailed functional role. In many others, while some design principles can be inferred, the detailed functional circuitry requires further investigation.

---

¹The development of Sindbis virus as a tracer has been used to advantage in several publications by Takeshi Kaneko and collaborators. Unfortunately, owing to illness, Prof. Kaneko could not contribute a chapter to this volume.

Chapter 1

Axonal Projection of Olfactory Bulb Tufted and Mitral Cells to Olfactory Cortex

Kensaku Mori^1,2, ¹Department of Physiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, ²Japan Science and Technology Agency, CREST, Tokyo, Japan

Abstract

Projection neurons in the sensory afferent pathways are structurally and functionally differentiated into distinct types, each type giving rise to specific sensory processing streams. In the olfactory afferent pathways, tufted cells and mitral cells in the olfactory bulb are two major types of projection neurons receiving synaptic inputs from nasal olfactory sensory neurons and projecting axons to the olfactory cortex. Tufted cells and mitral cells form distinct local neuronal circuits within the olfactory bulb and convey their signals to the olfactory cortex at different time windows during the inhalation–exhalation sniff cycle. Furthermore, tufted cells and mitral cells show strikingly different branching pattern of axons; the former projecting selectively to focal targets and the latter dispersedly in the olfactory cortex. We propose a hypothesis that tufted cells and mitral cells function complementarily both in time and space and play distinct functional roles in “bindings” at neuronal circuits in the olfactory cortex.

Keywords

Olfaction; tufted cell; mitral cell; axonal projection; respiration

1.1 Tufted Cells and Mitral Cells are Projection Neurons in the Olfactory Bulb, Conveying Odor Information to the Olfactory Cortex

Olfactory perception depends critically on respiration cycles. The central olfactory system in the brain receives odor information of the external world during the inhalation phase (on-line phase) of the respiration cycle, whereas it is isolated from the external world during the exhalation phase (off-line phase) (Kepecs et al., 2006; Mainland and Sobel, 2006; Mori and Manabe, 2014; Mori et al., 2013). Therefore, a major question in the exploration of the olfactory system in the mammalian brain is how and in which timing during a single inhalation–exhalation cycle the central olfactory system transforms external odor information into emotional responses and motivated behavior outputs.

Figure 1.1 illustrates the characteristic structural organization of the afferent pathways of the olfactory system. During the inhalation phase, odor molecules (odorants) are inhaled into the nasal cavity and detected by odorant receptors expressed on the cilial surface membrane of olfactory sensory neurons in the nasal epithelium (Buck and Axel, 1991). Mouse olfactory epithelium demonstrates approximately 1000 different odorant receptor species, and each olfactory sensory neuron ...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Preface
• Foreword
• Acknowledgments
• Introduction
• Section I: Microcircuitry
• Section II: Axon Dynamics
• Section III: Axon Guidance
• Section IV: Tractography
• Conclusion
• Index