Chapters 6 and 7 describe the mechanisms underlying induction and expression of plasticity in the barrel cortex. In using the term plasticity, synaptic plasticity is meant implicitly, including not only the second-to-second changes that ensue during in vitro forms of plasticity such as LTP and long-term depression (LTD) but also the growth of pre- and postsynaptic elements of the synapse that occur over longer time scales. This chapter deals with the cellular evidence on the nature of synaptic plasticity mechanisms, while Chapter 7 deals with the systems level evidence for plasticity induced in the whole animal. The extent to which all plasticity mechanisms in the cortex are underpinned by synaptic plasticity is, of course, a subject of much debate and an issue we take up in the following pages.

Historically, synaptic plasticity has been studied extensively in hippocampus, visual cortex and barrel cortex. In some respects, plasticity studies in barrel cortex have caught up with those parallel investigations in the visual system and in some areas overtaken them. There are a number of reasons why this has happened, including the ease of manipulation of the peripheral receptors in the whisker system, the introduction of transgenics and knockouts in rodents and the invention of the thalamocortical slice preparation (Agmon and Connors, 1991). Although synaptic plasticity is not as well understood in the barrel cortex as in the hippocampus, even at this early stage it is clear that some differences exist between the two systems.

Since the 1970s, a detailed description of the anatomical pathways of the vibrissae system has evolved in the literature. The process has been facilitated by the ability to discern topographical arrangements at each stage of the somatosensory pathway by virtue of the barrel pattern itself and by the careful application of dye-tracing techniques by a number of laboratories. The connectivity of the barrel cortex still remains a challenge because of its intricate complexity, and it has only recently become ammenable to description as a result of dual intracellular recording and glutamate uncaging methodologies. In this chapter, we describe the pathways leading from the whisker follicles (Section 2.1) through the brainstem (Section 2.2) and thalamus (Section 2.3) to the barrel cortex (Section 2.4). Where appropriate, the physiology of subcortical pathways are discussed but a more detailed consideration of barrel cortex physiology is reserved for subsequent chapters. We begin here at the periphery by considering the anatomy of the vibrissa follicle.

Whisker follicle innervation

The follicle itself is composed of a series of concentrically arranged membranes. Closest to the vibrissa itself lies a thick basement membrane, often referred to as the glassy membrane, which ensheaths the vibrissa hair (Figure 2.1). Outside the glassy membrane is a mesenchymal sheath that forms the inner surface of the follicle sinus. Outside this lies the vascular sinus itself, which is bounded on the outside by another thick highly collagenous membrane that forms the outside of the follicle sinus.

Understanding the brain – its structure, connections, functions and the genetic bases of these properties – remains the central riddle in biology if not science. A number of different strategies to attack this issue have focused on many aspects of the nervous system and have, at an ever-increasing pace, begun to home in on the core questions. In neuroscience, the details of the underlying mechanisms have become tractable in the past decade and a half. But, similar to understanding the relationship of atomic interactions to the weather that they must cause, taking detailed neural mechanisms back to the level of the functioning nervous system has been arduous. Nevertheless, there is great promise that in the not too distant future the problem will be solved. Seemingly complicated behaviors and strategies could be explained entirely from understanding the components, their connectivity, their functions and their cohorts.

This quest could be made easier by focus on a part of the brain that is both easily accessible and straightforward to study and that provides a “standard” context to position data of different sorts from different studies by different laboratories. Further, it would offer greater promise if it could be manipulated genetically, developmentally and behaviorally and was reasonably similar to many other brain regions so as to permit ready translation to them. In this volume, Kevin Fox (whom I have had the good fortune to know since he worked in St. Louis in the late 1980s and early 1990s) has elegantly and concisely summarized the major findings on a region of cortex that we have both studied.

This chapter describes how the barrel cortex processes sensory information from a systems viewpoint. Several questions are addressed, such as how information is coded, what processing a cortical column performs and how active touch might work. While considerable progress has been made in recent years in tackling these questions, it is not yet possible to answer them fully. Here we approach sensory processing from the viewpoint that it is possible to shed light on several classic questions in the general field of sensory physiology by studying the barrel system.

One of the classic questions in sensory physiology concerns how information is coded and whether information travels in specialized channels that form labeled lines of information. The issue is particularly pertinent in the barrel system where the very purpose of the anatomical pattern of the whiskers and barrels seems to indicate an affirmative answer. However, while labeled-line processing is a good first-order approximation for the barrel system (Section 5.1), many studies in recent years show how barrel cortex integrates information from different whiskers. The tension between these two ideas has driven many studies in this field and they are treated from two complementary but inverse viewpoints in Section 5.2, which deals with cortical domains driven by single whiskers, and Section 5.3, which deals with receptive fields.

Section 5.4 on dynamic sensory processing looks at the question of how active touch can be understood and the degree to which studies on passive touch (treated in earlier sections of the chapter) can inform this understanding.

The cerebral cortex is well known for its complexity. At least 20 different cortical cell types can be classified with ease, and by many accounts this would represent a conservative estimate. Recent studies have used gene expression to identify cell types within the cortex and revealed a high degree of cell diversity (Sugino et al., 2006). It is not the purpose of this chapter to describe every nuance of cell type exhaustively, and indeed there are many excellent accounts elsewhere (Peters and Jones, 1984; Markram et al., 2004; Sugino et al., 2006). Instead, a brief summary of the salient features is given in the following sections as a prelude to describing their synaptic properties and some of the general features of cortical circuitry to emerge from studies in recent years. Neurons in the cortex are almost entirely glutamatergic and thus excitatory, or GABAergic and thus inhibitory (Section 3.3). The following two sections look at the excitatory and inhibitory cell types.

Excitatory cells

There are three main types of excitatory cell in the cortex: the spiny stellate, the star pyramid and the pyramidal cell. The star pyramid is intermediate in form between the stellate and pyramidal cell. The main features of the three cell types are described below, beginning with the spiny stellate and star pyramidal cells and ending with the diversity of pyramidal cell types in individual cortical layers.

Spiny stellate cells

Spiny stellate cells are characterized by, and indeed named after, their star-shaped dendritic pattern.

This chapter describes the formation of the barrel cortex from the birth of the cells through to maturation of synaptic circuits. Special consideration is given to formation of the distinctive somatotopic pattern in the barrel field that has captured the imagination of so many scientists over the years. Pattern formation is, of course, a field within developmental science in its own right, of which formation of the somatotopic pattern in the barrel field is an interesting example. Somatotopic pattern formation per se is, therefore, treated in a section on its own. Barrel formation, however, does not raise the same issues and could just as easily be concerned with the formation of a single barrel as with a pattern of barrels. For these reasons, pattern formation and barrel formation are treated in separate sections. Of course the cellular aggregates composing the barrels themselves also make a pattern (Chapter 1), but as we shall see the pattern is present in the thalamocortical afferents before they reach layer IV where the barrels form, and in some circumstances the pattern itself can form in the thalamocortical afferents without the barrels forming. Therefore, the sections on pattern formation concentrate on the origin of the pattern itself, including the role of the peripheral innervation (Section 4.2), while the sections on barrel formation concentrate on the behavior of the cellular aggregates that compose the walls of the barrels (Section 4.3).

This chapter differs from those preceding it in that it does not treat a single theme but several. Rather than concentrate on one particular field of barrel cortex research, this chapter explores research in several new and emerging fields. Each field is characterized by a strong continuing development of methodology. In each case, barrel cortex is either the central focus of the research or is particularly well suited to help to further research in an allied field. The area of cortical blood flow and stroke research is a good example of the latter category. Many of the common cortical strokes that lead to paralysis are caused by occlusions that involve or affect the middle cerebral artery, which supplies the somatosensory cortex in general and the barrel cortex in rats and mice. Stroke research is in many ways ideally suited to study in barrel cortex because the cortical tissue affected by the stroke can be readily defined from the barrel field histology and the clinically relevant artery can be occluded to observe its effect on barrel cortex blood flow, angiogenesis, cell death and recovery of function.

Arguably some of the topics treated in this section warrant chapters of their own or could add considerably to the previous chapters in this book. The reason they have been grouped together in one chapter stems from two main factors.

The field of barrel cortex research has grown rapidly over the past few years. Today, studies are directed not only at understanding the barrel cortex itself but also at understanding issues in related fields using the barrel cortex as a model system. In the three years it has taken to write this book, over 300 papers have been published on barrel cortex. While this rising tide of information has made writing a challenge, the fundamental studies of the preceding 34 years have provided a solid foundation and context in which to place the new work. Fortunately for me, the story has been enhanced by research in recent years and not entirely rewritten by it.

One of the reasons for writing this book has been the realization that barrel cortex research has matured to a point where a survey and a summary has become possible. The field has been characterized by classic studies that illuminate this and other areas of neuroscience and by a constant innovation in techniques and ideas. In fact, the barrel cortex has served as a test-bed system for several new methodologies, partly because of its unique and instantly identifiable form, and partly because the species that have barrels, the rodents, are the most commonly used laboratory mammal. The classic studies on the basic anatomy and physiology of this cortical area have certainly facilitated subsequent studies on barrel cortex. Two fundamental innovations have driven the field further.

Introduction

The barrel cortex is a remarkable structure. Its form has captured the imagination of researchers for decades and its versatility has ensured that it finds a place in each new wave of neuroscience research. Since its discovery by Woolsey and Van der Loos in the early 1970s, researchers have used barrel cortex to study some of the most pressing questions in neuroscience. How does the cortex develop? How does active touch work? What makes neurons plastic? In each case, the value of the barrel cortex has been to help neuroscientists to relate structure with function through its unique and easily defined form.

In order to understand how these questions are being addressed currently, it is useful to understand some of the basic structural and functional features of the barrel cortex. The first three chapters of this book address some of the fundamental anatomy and physiology of the barrel cortex. For the expert in the field, most of what is written in these chapters will probably be quite familiar but will hopefully still serve as a useful reference to the original studies. While most of the original anatomical studies span the 1970s and 1980s, new neuroanatomical findings are still being described into the current century. Curiously, a review of this anatomical literature has not previously been written. For those less familiar with barrel cortex, the anatomical pathways linking the periphery to barrel cortex are described in Chapter 2 along with the intracortical connections, the study of which, at the time of writing, is still an active area of research.

Plasticity is an important topic in neuroscience, both from a philosophical and a practical viewpoint. Plasticity is involved in development, learning and memory and in shaping the nervous system's response to injury and disease. With regard to development, some topics have been covered in Chapter 4, but here we concentrate in more detail on the mechanisms of plasticity rather than their developmental sequence and consequences for development. On the question of learning and memory, in Section 7.2 we look at the extent to which synaptic plasticity mechanisms are activated by changes in sensory experience. This issue relates in a general way to the means by which experience creates memories. Sensory experience can induce lasting memories and memory is thought to depend on synaptic plasticity. Therefore, understanding how sensory experience induces synaptic plasticity is germane to understanding learning and memory. In both cases, experience changes synaptic function. On the question of the nervous system's response to injury, we treat this topic separately from the general treatment of experience-dependent plasticity because even though it may involve components of the latter it certainly involves other factors too (Section 7.5). In many ways, this may be the more urgent category of plasticity to tackle because a full understanding of injury-induced plasticity may lead to therapies for the consequences of damage to peripheral or central structures.

The early studies on somatosensory cortical plasticity were concerned with the cortical response to peripheral injury.