Handbook of Basal Ganglia Structure and Function

Heinz Steiner, Kuei Y. Tseng

• Publisher: Academic Press
• Year: 2016
• eBook ISBN: 9780128025260
• Edition: 2
• Topic: Biological Sciences
• Subtopic: Neuroscience
• Index: Biological Sciences

Handbook of Basal Ganglia Structure and Function, Second Edition, offers an integrated overview of the structural and functional aspects of the basal ganglia, highlighting clinical relevance. The basal ganglia, a group of forebrain nuclei interconnected with the cerebral cortex, thalamus, and brainstem, are involved in numerous brain functions, such as motor control and learning, sensorimotor integration, reward, and cognition. These nuclei are essential for normal brain function and behavior, and their importance is further emphasized by the numerous and diverse disorders associated with basal ganglia dysfunction, including Parkinson's disease, Tourette's syndrome, Huntington's disease, obsessive-compulsive disorder, dystonia, and psychostimulant addiction. This updated edition has been thoroughly revised to provide the most up-to-date account of this critical brain structure. Edited and authored by internationally acclaimed basal ganglia researchers, the new edition contains ten entirely new chapters that offer expanded coverage of anatomy and physiology, detailed accounts of recent advances in cellular/molecular mechanisms and cellular/physiological mechanisms, and critical, deeper insights into the behavioral and clinical aspects of basal ganglia function and dysfunction. - Synthesizes widely dispersed information on the behavioral neurobiology of the basal ganglia, including advances in the understanding of anatomy, cellular/molecular and cellular/physiological mechanisms, and behavioral and clinical aspects of function and dysfunction - Written by international authors who are preeminent researchers in the field - Explores, in full, the clinically relevant impact of the basal ganglia on various psychiatric and neurological diseases

Chapter 1

The Neuroanatomical Organization of the Basal Ganglia

C.R. Gerfen¹ and J.P. Bolam², ¹Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, MD, United States, ²MRC Anatomical Neuropharmacology Unit, Oxford University, Oxford, United Kingdom

The basal ganglia comprise a subcortical brain system through which the cerebral cortex affects behavior. The principal input structure is the striatum, whose GABAergic medium spiny neurons (MSNs) are the target of excitatory cortical and thalamic inputs. The output of the basal ganglia are GABAergic neurons in the internal segment of the globus pallidus and substantia nigra pars reticulata, which provide inhibition to the thalamus and midbrain motor areas including the superior colliculus and pedunculopontine nucleus. Activity in these output pathways is regulated by opponent effects of the two main MSN subtypes, those expressing the D1 dopamine receptor, which project directly to the output nuclei, and those expressing the D2 dopamine receptor, which project indirectly through the external segment of the globus pallidus and subthalamic nucleus. In addition, the striatum is organized into patch and matrix compartments, which differentially regulate substantia nigra pars compacta dopamine neurons and GABAergic output pathways.

Keywords

Cortex; striatum; globus pallidus; substantia nigra; subthalamic nucleus; thalamus; dopamine; GABA; medium spiny neuron; cholinergic interneuron

Outline

I. Introduction 3

II. Overview of Basal Ganglia Organization 5

III. The Corticostriatal System 6

A. Subtypes of Corticostriatal Neurons 7

B. Organization Patterns of Corticostriatal Afferents 8

IV. Striatum 9

A. Medium Spiny Projection Neurons 9

B. Synaptic Inputs to Medium Spiny Neurons 9

C. Striatal Interneurons 12

V. Output Systems of the Striatum 13

A. The Direct and Indirect Pathways 13

B. Other Nuclei of the Indirect Pathway 16

C. Dual Projections Within Basal Ganglia Circuits 18

VI. Basal Ganglia Output Nuclei: GPi and Substantia Nigra 19

A. Cell Types 20

B. Inputs 20

C. Outputs 20

VII. The Nigrostriatal Dopamine System 21

A. Dorsal Tier Versus Ventral Tier Dopamine Neurons 21

B. Inputs to Dopamine Neurons 23

VIII. Striatal Patch–Matrix Compartments 23

A. Cortical Inputs 23

B. Thalamic Inputs 24

C. Striatal Outputs 24

D. General Patch–Matrix Organization 26

IX. Summary 26

References 27

I Introduction

The basal ganglia connect the cerebral cortex with neuronal systems that transform activity in the cortex into directed behavior. Functions attributed to the basal ganglia include motor learning, habit formation, and the selection of actions based on desirable outcomes (Cisek and Kalaska, 2010; Graybiel et al., 1994; Hikosaka et al., 2000; Mink, 1996; Redgrave et al., 1999; Wichmann and DeLong, 2003; Yin and Knowlton, 2006). Most cortical areas provide inputs to the basal ganglia, which in turn provide outputs to brain systems that are involved in the generation of behavior. Among the behavior effector systems targeted are thalamic nuclei that project to those frontal cortical areas involved in the planning and execution of movement; midbrain regions including the superior colliculus, which contributes to the generation of eye movements; the pedunculopontine nucleus, which is involved in orienting movements; and hypothalamic systems associated with autonomic functions.

Two points concerning the function of the basal ganglia are emphasized. First, while the basal ganglia connect the cerebral cortex with a wide range of behavior effector systems, the basal ganglia operate in parallel with other output systems of the cerebral cortex. These other corticofugal systems may have a more primary role in the actual generation of behavior. For example, the frontal cortical areas involved in the planning and execution of movement behavior provide direct output, via direct corticospinal projections, that is responsible for the generation of movement. Thus, it remains unclear whether the basal ganglia should be thought of as playing a direct or modulatory role in specifying behavior. Second, while the basal ganglia are connected with a wide range of behavior effector systems, not all regions of the basal ganglia are connected with all of the output systems. In other words, there is a conservation of regional functional organization of the cerebral cortex in the connections of the basal ganglia. In considering the neuroanatomical organization of the basal ganglia, there are differing views. On the one hand, the basal ganglia have been proposed to provide for interactions between disparate functional circuits, for example, between the so-called limbic and nonlimbic functions. Another view holds that there are parallel functional circuits, in which distinct functions are for the most part maintained, or segregated, one from the other. This review is biased toward the view that there is maintenance of functional parallel circuits in the organization of the basal ganglia, with considerable interactions between adjacent circuits (see also chapter: Integrative Networks Across Basal Ganglia Circuits).

Most details of the neuroanatomical and neurophysiological organization of basal ganglia circuits have first been established in rodents and confirmed in primates. Accordingly, the present review is mainly based on studies in rodents (as are the schemes used to illustrate the organizational principles). Several of the following chapters provide detailed information on the functional organization of the primate basal ganglia. What are the most significant differences in the organization between rodents and other mammals, notably primates? The most obvious differences between rodents and primates are those involving the gross anatomy of the nuclei of the basal ganglia. There are two major examples. The first is the striatum, which in the primate is subdivided into caudate nucleus and putamen by the internal capsule that provides a structural separation between these two nuclei. This structural separation does provide a gross separation of functional regions in the striatum in that the caudate nucleus is mainly the target of prefrontal cortical inputs, whereas the putamen is the target of motor and somatosensory inputs. As the cortical input to the striatum is in a large part responsible for its function, the caudate nucleus and putamen in the primate are to a major extent functionally distinct. However, the internal capsule does not provide a precise divider of functional zones and there is some overlap of inputs from prefrontal cortex to the putamen. In the rodent, which lacks such a distinct structural separation, there are nonetheless regional differences in the striatum that are comparable to those of the caudate and putamen, again determined by the regional distribution of inputs from different cortical areas.

The second major gross anatomical difference between rats and primates involves the globus pallidus (GP) (see chapter: Organization of the Globus Pallidus). In primates, the internal segment of the globus pallidus (GPi) is situated immediately adjacent to the external segment (GPe), whereas in rodents, the homologous nucleus is separated from the GPe and is embedded in the fiber tract of the internal capsule. In rodents, this nucleus has historically been termed the entopeduncular nucleus, which reflects its location. However, as this nucleus is functionally comparable to the GPi in primates, this nomenclature, GPi, is adopted for the present volume. Both nuclei represent, along with the substantia nigra pars reticulata (SNr) (see chapter: The Substantia Nigra Pars Reticulata), which is nearly identical in both rodents and primates, the output structures of the basal ganglia.

Despite the gross anatomical differences noted, the major connectional organization of the basal ganglia in rodents and primates is remarkably similar. Three of the major features of basal ganglia organization that will be dealt with in some depth in this review, the organization of direct and indirect output pathways of the striatum, the patch–matrix compartmental organization of the striatum, and the dual projections of individual striatal neurons have been demonstrated in both rodents and primates, and appear, in the main, nearly identical in organization.

Differences in the organization of the basal ganglia between rodents and primates may for the most part be attributed to the expanded cortex in primates. In primates, cortical fields are considerably elaborated and more precisely defined in terms of functional segregation of different cortical areas. While the organization of corticostriatal patterns appears to follow the same general principles in rodents and primates, the elaboration of more detailed precise mapping patterns predominate in the primate. Thus, in summary, the major organizational principles of the basal ganglia appear for the most part nearly identical in rodents and primates.

II Overview of Basal Ganglia Organization

The organization of the basal ganglia is intimately linked to that of the cerebral cortex, with distinct differences between those regions of the basal ganglia that receive inputs from neocortical, six-layered cortex, compared with those receiving inputs from allocortical areas. This review focuses primarily on the neocortical part of the basal ganglia. A general canonical organizational plan of the neocortical-related basal ganglia is described in Fig. 1.1. The components of this canonical basal ganglia system include the neocortex, the striatum, which includes the caudate–putamen and the core of the nucleus accumbens, the GPe, the subthalamic nucleus (STN), the GPi, the SNr, and the substantia nigra pars compacta (SNc).

Figure 1.1 Diagram of basal ganglia circuits. (A) The striatum receives excitatory corticostriatal and thalamic inputs. Outputs of the basal ganglia arise from the GPi and the SNr, which are directed to the thalamus, superior colliculus, and pedunculopontine nucleus (PPN). The striatum has two output pathways. The direct pathway is formed by D1 dopamine receptor (Drd1a)-expressing medium spiny neurons (D1-MSNs) that project to the GPi and SNr output nuclei. The indirect pathway originates from D2 receptor (Drd2)-expressing MSNs (D2-MSNs) that project only to the GPe, which together with the STN connects to the basal output nuclei. The direct and indirect pathways provide opponent regulation of the basal ganglia output interface. (B) Fluorescent image of a sagittal brain section from a mouse expressing eGFP under the control of the Drd1a promoter shows D1-MSNs in the striatum that project axons through the GPe, which terminate in the GPi/SNr and to some degree in the GPe. (C) Fluorescent image of a sagittal section from a Drd2-eGFP mouse shows that labeled MSNs (D2-MSNs) provide axonal projections that terminate in the GPe, but do not extend to the GPi or SNr. Source: From Gerfen, C.R., Surmeier, D.J., 2011. Modulation of striatal projection systems by dopamine. Annu. Rev. Neurosci. 34, 441–466 (Gerfen and Surmeier, 2011).

The major input to this system comes from layer 5 glutamatergic neurons from nearly all areas of the neocortex. The output of this system is provided by the GABAergic projection neurons in the GPi and the SNr. These outputs target thalamic nuclei that project to frontal cortical areas involved in the planning and execution of movement behavior; the intralaminar thalamic nuclei, which provide inputs to the neocortex and the striatum; the intermediate layers of the superior colliculus, which are involved in the generation of eye and head movements; and the pedunculopontine nucleus, which is involved in orienting movements of the body. In between the cortical inputs and the GABAergic output systems are the neuroanatomical circuits that comprise the prototypical bas...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• List of Contributors
• Preface
• Acknowledgments
• List of Abbreviations
• Part A. The Basal Ganglia System and Its Evolution
• Chapter 1. The Neuroanatomical Organization of the Basal Ganglia
• Chapter 2. The History of the Basal Ganglia: The Nuclei
• Chapter 3. The History of the Basal Ganglia: Cells and Circuits
• Chapter 4. The Conservative Evolution of the Vertebrate Basal Ganglia
• Chapter 5. Cell Types in the Different Nuclei of the Basal Ganglia
• Part B. Anatomy and Physiology of the Striatum
• Chapter 6. The Striatal Skeleton: Medium Spiny Projection Neurons and Their Lateral Connections
• Chapter 7. The Cholinergic Interneuron of the Striatum
• Chapter 8. GABAergic Interneurons of the Striatum
• Chapter 9. Dopaminergic Modulation of Glutamatergic Signaling in Striatal Spiny Projection Neurons
• Chapter 10. Endocannabinoid Signaling in the Striatum
• Chapter 11. Nitric Oxide Signaling in the Striatum
• Chapter 12. Role of Adenosine in the Basal Ganglia
• Part C. Anatomy and Physiology of Globus Pallidus, Subthalamic Nucleus, and Substantia Nigra
• Chapter 13. Organization of the Globus Pallidus
• Chapter 14. The Subthalamic Nucleus
• Chapter 15. The Substantia Nigra Pars Reticulata
• Chapter 16. Subtypes of Midbrain Dopamine Neurons
• Chapter 17. Neurophysiology of Substantia Nigra Dopamine Neurons: Modulation by GABA and Glutamate
• Chapter 18. Plasticity in Dopamine Neurons
• Chapter 19. Regulation of Extracellular Dopamine: Release and Uptake
• Part D. Network Integration
• Chapter 20. Organization of Corticostriatal Projection Neuron Types
• Chapter 21. Organization of Prefrontal-Striatal Connections
• Chapter 22. Gating of Cortical Input Through the Striatum
• Chapter 23. Regulation of Corticostriatal Synaptic Plasticity in Physiological and Pathological Conditions
• Chapter 24. The Thalamostriatal Systems in Normal and Disease States
• Chapter 25. The Tail of the Ventral Tegmental Area/Rostromedial Tegmental Nucleus: A Modulator of Midbrain Dopamine Systems
• Chapter 26. The Rostromedial Tegmental Nucleus: Connections With the Basal Ganglia
• Chapter 27. Integrative Networks Across Basal Ganglia Circuits
• Part E. Molecular Signaling in the Basal Ganglia
• Chapter 28. Receptors and Second Messengers in the Basal Ganglia
• Chapter 29. Regulation of Striatal Signaling by Protein Phosphatases
• Chapter 30. Neurotransmitter Regulation of Striatal Gene Expression
• Chapter 31. Psychostimulant-Induced Gene Regulation in Striatal Circuits
• Chapter 32. Epigenetics in Neuropathologies of the Basal Ganglia
• Part F. Basal Ganglia Function and Dysfunction
• Chapter 33. Investigating Basal Ganglia Function With Cell-Type-Specific Manipulations
• Chapter 34. Phasic Dopamine Signaling in Action Selection and Reinforcement Learning
• Chapter 35. Memory Systems of the Basal Ganglia
• Chapter 36. Abnormal Activities in Cortico-Basal Ganglia Circuits in Movement Disorders
• Chapter 37. Morphological Plasticity in the Striatum Associated With Dopamine Dysfunction
• Chapter 38. Neuroinflammation in Movement Disorders
• Chapter 39. Disease-Associated Changes in the Striosome and Matrix Compartments of the Dorsal Striatum
• Chapter 40. Etiology and Progression of Parkinson's Disease: Cross-Talk Between Environmental Factors and Genetic Vulnerability
• Chapter 41. Determinants of Selective Vulnerability of Dopamine Neurons in Parkinson's Disease
• Chapter 42. Parkinson's Disease: Genetics
• Chapter 43. Molecular Mechanisms of L-DOPA-Induced Dyskinesia
• Chapter 44. Cell Therapy in Parkinson's Disease: Understanding the Challenge
• Chapter 45. Cellular and Molecular Mechanisms of Neuronal Dysfunction in Huntington's Disease
• Chapter 46. Alterations of Synaptic Function in Huntington's Disease
• Chapter 47. Pathophysiology of Dystonia
• Chapter 48. Tourette Syndrome and Tic Disorders
• Chapter 49. Deep-Brain Stimulation for Neurologic and Neuropsychiatric Disorders
• Index