Advances in Behavioral Biology – serie

The neuronal cytoskeleton is a complex structure responsive to both intrinsic and extrinsic factors. Defined populations of neurons in the brains of patients with Alzheimer and several other neurodegenerative diseases contain abnormal filamentous accumulations which share elements with the cytoskeleton. Although there is a general consensus that these abnormal filaments do contain cytoskeletal elements, much debate remains regarding which cytoskeletal elements are incorporated and whether the cytoskeletal rearrangement is primary or secondary to other cellular changes. In this book these questions are addressed in a historical perspect­ ive in light of new data that allows the reinterpretation of previously reported results. Contributions are based on many of the major tech­ niques of modern biology including biochemistry, molecular biology, electron microscopy and immunocytochemistry. In the view of the editor, this volume is being written at a time when our understanding of the cytopathology of Alzheimer disease is moving from predominantly descriptive to both analytical and mechanistic. I hope that this contribution will provide impetus to speed this transi­ tion. George Perry Cleveland, Ohio vii ACKNOWLEDGEMENT The support of the Fidia Pharmaceutic Corporation for the computer­ generated color figure on page 65 is gratefully acknowledged.

This book represents the third in a series of International Conferences related to Alzheimer's (AD) and Parkinson's (PD) diseases. The first one took place in Eilat, Israel, in 1985; and the second one in Kyoto, Japan, in 1989. This book contains the full text of oral and poster presentations from the Third International Conference on Alzheimer's and Parkinson's Diseases: Recent Developments, held in Chicago, Illinois, U.S.A. on November 1-6, 1993. The Chicago Conference was attended by 270 participants. The Scientific Program was divided into nine oral sessions, a keynote presentation, and a poster session. The conference culminated in a Round Table Discussion involving all of the participants in the conference. The four and one-half day meeting served as an excellent medium for surveying the current status of clinical and preclinical developments in AD and PD. There were 59 oral presentations and 93 posters. This book incorporates a majority of both.

In August of 1991, a second Dartmouth International Workshop on the corpus callosum was convened to share and discuss the progress that had been made over the decade that had passed following the first workshop. A nucleus of basic and clinical scientists came together to discuss their work and the work of others in a field that has been broadened clinically by the addition of many new centers throughout the world that are now performing corpus callosotomy for intractable epilepsy. This text was stimulated by the participants' presentations and associated fertile discussions. It is compiled from the conference and subsequent studies. It reflects, both at the basic and clinical level, an important and expanding field of neural science endeavor. In keeping with the present and rapidly expanding field of outcomes assessment, callosotomy is again evaluated in light of a further decade of surgery and follow-up. Callosotomy continues to be a useful, palliative procedure and the indications for its use have been better established. The basic science section is a supplement to the first edition and elaborates progress in both new data and ideas. The section on experimental epilepsy models adds further support to the clinical rationale for callosotomy. Perhaps of greater importance is the contribution of experimental models to our understanding of the propagation of seizure activity. The section on the neuropsychology of the split brain patient demonstrates the continuing major contributions to the understanding of brain and behavior that pour forth from this cornucopia.

The endothelial cells of the cerebral vasculature constitute, together with perivascular elements (astrocytes, pcricytes, basement membrane), the blood-brain barrier (BBB), which strictly limits and specifically controls the exchanges between the blood and the cerebral extracellular spacc.The existence of such a physical, enzymatic, and active barrier isolating the central nervous system has broad physiological, biological, pharmacological, and patho­ logical consequences, most of which are not yet fully elucidated. The Cerebral Vascular Biology conference (CVB '95) was organized and held at the "Carre des Sciences" in Paris on July I 0-12, 1995. Like the CVB '92 conference held in Duluth, Minnesota, three years ago, the objectives were to provide a forum for presentation of the most recent progresses and to stimulate discussions in the ticld of the biology, physiology. and pathology of the blood-brain barrier. The Paris conference gathered more than !50 participants. including investigators in basic neuroscience, physicians. and stu­ dents, who actively contributed to the scientific program by their oral or poster presentations. This volume contains a collection of short articles that summarize most of the new data that were presented at the conference. Six thematic parts focus on physiological transports. drug delivery, multidrug resistance P-glycoprotein, signal transduction at the BBB. interactions between the immune system and the cerebral endothelial cells, and the blood-brain barrier-related pathologies in the central nervous system. In addition, two introductory articles present new insights in the rapidly evolving topics of cerebral angiogenesis and gene transfer to the brain.

This volume, The Basal Ganglia V, is derived from proceedings of the fifth Triennial Meeting of the International Basal Ganglia Society (IBAGS).

This book represents the fourth ina series of international conferences related to Alzheimer's (AD) and Parkinson's (PO) diseases. This book incorporates the proceedings of the Fourth International Conference on Pro­ gress in Alzheimer's and Parkinson's Diseases, held in EHat, Israel, on May 18-23, 1997.

This book is devoted to the neuropsychological description of childhood epilepsy, a neurolo- cal condition that constitutes one of the most prevalent forms of chronic and disabling childhood illnesses. Indeed, one child out of 20 experiences one or more seizures before the age of 5, and one in a hundred develops epilepsy as a chronic disorder. Approximately half of these children with epilepsy display academic difficulties and/or behavioral disorders. Moreoever, it is now believed that a sizable proportion of children with learning disability suffer from undiagnosed epilepsy. While a great number of textbooks have been devoted to various medical aspects of chi- hood epilepsy (diagnosis, genetics, etiology, drug and surgical treatment, etc.), there have been no comprehensive accounts of the cognitive consequences of this condition. Advance of medical knowledge has shown that childhood epilepsy should not be considered as a single disorder but encompasses a whole range of different conditions that exhibit specific clinical EEG and outcome characteristics. It is not becoming apparent that these various clinical entities have different cognitive expression that yet need to be specified. The purpose of this book is to provide a complete up-to-date analysis of this multi-faceted pathology.

1h The 5 International Conference on the Progress in Alzheimer's Disease and Parkinson's 51 1 Disease took place from March 31 to April 5 \ 2001 in Kroto, Japan. This international 1 conference was organized as a joint Congress with the 9 International Catecholamine Symposium. A total of 1258 clinicians and researchers participated in this joint congress 1h from 38 countries in the world. This book represents the proceedings of the 5 Conference on Alzheimer's and Parkinson's disease. The International Conference on the Progress in Alzheimer's and Parkinson's disease was first launched by Professor Abraham Fisher of Israel and Professor Israel Hanin of USA. The first conference was held in Eilat, Israel in 1985. The second conference was organized in Kyoto, Japan in 1989; the third one in Chicago, USA, in 1993, and the fourth one in Eilat, Israel in 1997. The International Catecholamine Symposium (ICS) is an international meeting devoted to the development of basic as well as clinical research on catecholamines. The first Catecholamine Symposium was held in Bethesda, USA in 1958. Since then this symposium has occurred every 5 years. Professor Toshiharu Nagatsu was appointed as 1h the president of the 9 International Catecholamine Symposium, which was to be held in 200 I also in Japan. Therefore, we decided to organize a joint congress of the two meetings, because there is much overlap in research between Alzheimer's disease, Parkinson's disease, and catecholamines. We thank Professor Nagatsu very much for agreeing to organizing this joint congress.

This volume, The Basal Ganglia VII, is derived from the proceedings ofthe Seventh Triennial Meeting of the International Basal Ganglia Society (IBAGS). The Meeting was held from II - 15 February 2001 at The Copthorne Resort, Waitangi, Bay of Islands, New Zealand, the site of the signing of the Treaty ofWaitangi in 1840 and the traditional birth-place of the New Zealand Nation. As at previous Meetings, our aim was to hear and discuss new ideas and research developments on the basal ganglia and the implications of these findings for novel treatment strategies for basal ganglia disorders. The International Basal Ganglia Society (IBAGS) was founded in September 1983 when a small group of about 50 neuroscientists and clinicians with a passion for research on the basal ganglia met for a three day meeting in a small isolated seaside resort, Lome, 150km from Melbourne in Australia. The meeting was organised by John McKenzie and was so successful that the participants decided to establish IBAGSand to meet every 3 years at an isolated seaside resort in different countries of the world.

The field of catecholamine research has not undergone comprehensive review for four years (since 1998). In the interim, a tremendous amount of new information, obtained using molecular, genetic, neurochemical and nuclear scanning techniques, has substantiated the important roles of catecholamine systems in development, cardiovascular function, psychiatric disorders, neurodegenerative diseases and metabolism. This volume, based on the Ninth International Catecholamine Symposium, should have a substantial and lasting impact on medical science.

This volume, the sixth in the IBAGS series, summarizes major contributions in clinical and basic research on the basal ganglia. The sixth meeting of the Society was held on Cape Cod, in the state of Massachusetts, USA, in October, 1998. Altogether 16 countries were represented by 227 participants. This volume contains papers contributed by participants. The focus of the sixth triennial IBAGS meeting, and of this volume, was to bring to­ gether leaders in basic and clinical science to address two sets of still-persisting questions in the field. The first set focuses on the functions of the basal ganglia in health and disease: What are the core functions of the basal ganglia and cortico-basal ganglia loops? How are these core functions disrupted in disorders affecting the basal ganglia? How do we account for the broad range of behaviors affected by basal ganglia disorders and for the increasing evidence that the basal ganglia influence cognitive as well as motor functions? These issues are addressed in the first five sections of the current volume, which summarize advances in the study of basal ganglia disorders based on studies in humans (Section 1), new results obtained with experimental animal models of basal ganglia disorders (Section 2), results of experiments on information coding in the basal ganglia (Section 3) and new information about functions of the basal ganglia related to learning and adaptive motor control (Section 4).

Proceedings of the Sixth International Conference on Kindling. Speakers at the conference will write chapters summarizing their current cutting-edge research on the kindling of seizures and related phenomena in epilepsy. The Kindling Conferences and the books arising from them (Kindling, Kindling 2-Kindling 5) have provided valuable summaries of the ongoing research on seizure development, with an emphasis on mechanisms, consequences, and potential treatments that might offset epileptogenesis. The general themes of talks and chapters at the Sixth Conference on Kindling are: pathogenesis, behavioral effects, drugs and interventions against kindling, and clinical relevance.

The aim of the International Meetings of the Basal Ganglia Society (IBAGS) is to provide a unique environment for the open presentation and discussion of new and challenging information about the basal ganglia as it relates to health and disease, covering all areas of basic science and research. Specific topics of the proceedings of this Eighth International Triennial Meeting of the Basal Ganglia Society include behavior, circuitry, functional imaging, modelling, movement disorders, neuropathology, neurotransmitters, pharmacology, physiology, plasticity, treatments for basal ganglia disorders, ventral systems, health and disease, immunology and basal ganglia, and much more.

Proceedings of the 7th International Conference on Alzheimer’s Disease and Parkinson’s Disease (ADPD), held March 9-13, 2005 in Sorrento, Italy.The subject matter of the ADPD conferences is unique in that it deals not only with issues related individually to Alzheimer’s disease and Parkinson’s disease, but also with the integration of these and other related diseases. The most up-to-date techniques and research findings are illustrated in this volume, covering topics such as immunology, neuroscience, pharmacology, genetics, molecular biology, biochemistry and the history, epidemiology, clinical phenomenology, diagnosis, imaging, treatment ,and future perspectives of Alzheimer’s and Parkinson’s Diseases.

The aim of the International Basal Ganglia Society (IBAGS) is to further our understanding of normal basal ganglia function and the pathophysiology of disorders of the basal ganglia, including Parkinson's disease, Huntington's disease, and schizophrenia. Each triennial meeting of IBAGS brings together basic research scientists from all disciplines as well as clinicians who are actively involved in the treatment of basal ganglia disorders, to discuss the most recent advances in the field and to generate new approaches and ideas for the future.This volume comprises the proceedings of the 9th meeting of IBAGS, held in Egmond aan Zee, The Netherlands, September 2nd-6th, 2007.

This book is devoted to the neuropsychological description of childhood epilepsy, a neurolo- cal condition that constitutes one of the most prevalent forms of chronic and disabling childhood illnesses. Indeed, one child out of 20 experiences one or more seizures before the age of 5, and one in a hundred develops epilepsy as a chronic disorder. Approximately half of these children with epilepsy display academic difficulties and/or behavioral disorders. Moreoever, it is now believed that a sizable proportion of children with learning disability suffer from undiagnosed epilepsy. While a great number of textbooks have been devoted to various medical aspects of chi- hood epilepsy (diagnosis, genetics, etiology, drug and surgical treatment, etc.), there have been no comprehensive accounts of the cognitive consequences of this condition. Advance of medical knowledge has shown that childhood epilepsy should not be considered as a single disorder but encompasses a whole range of different conditions that exhibit specific clinical EEG and outcome characteristics. It is not becoming apparent that these various clinical entities have different cognitive expression that yet need to be specified. The purpose of this book is to provide a complete up-to-date analysis of this multi-faceted pathology.

This book is based on invited presentations at the Ninth International Catecholamine Symposiwn. Over several decades, each International Catecholamine Symposiwn (ICS) has provided a uniquely important forwn for updating basic as well as clinical research on the catecholamines, dopamine, norepinephrine, and epinephrine. The first ICS took nd n1 place in Bethesda, Maryland, in the USA in 1958; the 2 in Milan, Italy in 1965; the 3 th in Strasbourg, France in 1973; the 4th in Asilomar, California, USA in 1978; the 5 in th th Goteborg, Sweden in 1983; the 6 in Jerusalem, Israel,in 1987; the 7 in Amsterdam, th Netherlands in 1992; and the 8 in Asilomar, California, USA in 1996. th The 9 International Catecholamine Symposiwn (9ICS) was held in Kyoto, Japan, th March 31-April 5, 2001. This ICS was held concurrently with the 5 International th Conference on Progress in Alzheimer's and Parkinson's Disease (5 ADPD). These international meetings were coordinated to be a joint international congress. Catecholamines and related neurotransmitters and neuromediators play important roles in the pathogenesis of symptoms and neurodegenerative processes of Alzheimer's disease and Parkinson's disease. Therefore, the Joint Congress provided an opportunity for investigators and clinicians working in these fields to exchange their· most recent investigational results and clinical experiences. This Joint International Congress turned out to be an enormous success, attended by 1258 participants from 38 countries, in an enthusiastic and pleasant atmosphere.

Proceedings of the Sixth International Conference on Kindling. Speakers at the conference will write chapters summarizing their current cutting-edge research on the kindling of seizures and related phenomena in epilepsy. The Kindling Conferences and the books arising from them (Kindling, Kindling 2-Kindling 5) have provided valuable summaries of the ongoing research on seizure development, with an emphasis on mechanisms, consequences, and potential treatments that might offset epileptogenesis. The general themes of talks and chapters at the Sixth Conference on Kindling are: pathogenesis, behavioral effects, drugs and interventions against kindling, and clinical relevance.

Proceedings of the 7th International Conference on Alzheimer’s Disease and Parkinson’s Disease (ADPD), held March 9-13, 2005 in Sorrento, Italy.The subject matter of the ADPD conferences is unique in that it deals not only with issues related individually to Alzheimer’s disease and Parkinson’s disease, but also with the integration of these and other related diseases. The most up-to-date techniques and research findings are illustrated in this volume, covering topics such as immunology, neuroscience, pharmacology, genetics, molecular biology, biochemistry and the history, epidemiology, clinical phenomenology, diagnosis, imaging, treatment ,and future perspectives of Alzheimer’s and Parkinson’s Diseases.

''Emphasis on new issues and emerging concepts insures that the information presented is still timely...A compelling source of information on recent research in the field.'' ---Journal of Chemical Neuroanatomy, May 1997

This book is devoted to the description of agenesis of the corpus callosum, a congenital malformation of midline structures in the brain that may be regarded as a natural model of the "split-brain. " First reported by Rei! in 1812, this anomaly has since been described by several investigators. Interest in this malformation was revived in the 1970s by studies of interhemispheric transfer in Bogen and Vogel's commissurotomized patients and the subsequent findings by Sperry that acallosal patients were devoid of the typical disconnection deficits found in patients with surgical transection of the corpus callosum. Since this seminal work, the bulk of neuropsychological research on callosal agenesis has focused on the particulars of interhemispheric transfer and integration. An ever-growing literature has emerged on the subject, attempting to specify the extent and limits of neural plasticity in a nervous system that has evolved in the absence of the most important interhemispheric pathway. Whilst callosal agenesis proves to be an excellent model of cerebral plasticity, it has to be pointed out that this anomaly is often associated with other malformations and neurological diseases that may result in different degrees of mental retardation or other cognitive and sensorimotor deficits. In this context, neurological research on callosal agenesis has concentrated on the description of various syndromes associated with this pathology as well as on the attempt to specify its neurobehavioral manifestations.

The neuronal cytoskeleton is a complex structure responsive to both intrinsic and extrinsic factors. Defined populations of neurons in the brains of patients with Alzheimer and several other neurodegenerative diseases contain abnormal filamentous accumulations which share elements with the cytoskeleton. Although there is a general consensus that these abnormal filaments do contain cytoskeletal elements, much debate remains regarding which cytoskeletal elements are incorporated and whether the cytoskeletal rearrangement is primary or secondary to other cellular changes. In this book these questions are addressed in a historical perspect­ ive in light of new data that allows the reinterpretation of previously reported results. Contributions are based on many of the major tech­ niques of modern biology including biochemistry, molecular biology, electron microscopy and immunocytochemistry. In the view of the editor, this volume is being written at a time when our understanding of the cytopathology of Alzheimer disease is moving from predominantly descriptive to both analytical and mechanistic. I hope that this contribution will provide impetus to speed this transi­ tion. George Perry Cleveland, Ohio vii ACKNOWLEDGEMENT The support of the Fidia Pharmaceutic Corporation for the computer­ generated color figure on page 65 is gratefully acknowledged.

Nicotine is the major factor in the continuation of the smoking habit among humans. On December 2-4, 1985, under the sponsorship of the Tobacco and Health Research Institute in Lexington, Kentucky, leading scientists from around the world whose research efforts have focused on the role of nicotine in the tobacco habit participated in an International Symposium to provide the most comprehensive and ~xtensive coverage of this topic so far. The material discussed was in the forefront of man's knowledge about nicotine, and both lectures and question and answer sessions were stimulating and enlightening. This publication contains the manuscripts presented at the Symposium, along with an Overview prepared by selected individuals. Lecture and poster session topics are delineated more fully in the Overview. This volume is expected to serve as a definitive reference on nicotine as it relates to the tobacco habit. Symposium sessions were arranged under four headings: (1) behavioral effects of nicotine and nicotine~ependence in humans and animals, (2) neurohumoral regulation of neuroendocrine and cardiovascular function by nicotine, (3) neuropharmacology of nicotine, and (4) neurochemistry. This was the first assembly of this magnitude of scientists who had devoted years of research to nicotine and its effects. Indeed, it was a pleasure to have sponsored this important event. Dr. Lay ten Davis, Director Tobacco and Health Research Institute Cooper and Alumni Drives Lexington, KY 40546-0236 v ACKNOWLEDGMENTS The Editors of this volume express sincere appreciation to all of the contributors. Special acknowledgments are given to Ms.

The i nterna ti ona 1 symposi a on transcutaneous monitori ng have dea It with the interaction between ideas and research, the introduction of unconventional techniques into clinical practice, and the joint efforts of researchers, clinicians, and industry to design and manufacture prac­ tical equipment for noninvasive monitoring. The First International Symposium on Continuous Transcutaneous Blood Gas Monitoring took place in Marburg, West Germany, from May 31 to June 2, 1978. This was the first major international meeting exclusively devoted to transcutaneous blood gas monitoring, and it was attended by the scientists who had developed this technique or had been \'Jorking with it, by a large number of doctors, mainly neonatologists who had just begun to use the technique or hoped to do so, and, finally, a rather large number of representatives of industry. The second symposium, with the same title, was held in Zurich, Switzerland, October 14-16, 1981. This time the focus was, to a large extent, on transcutaneous PC0 monitori ng, for whi ch equipment had become 2 commercially available only a short time before. Fetal monitoring was also discussed at length, as was the use of the transcutaneous techniques in other fields, such as vascular surgery and experimental animal research. The third symposium, October 1-4, 1986, was again held in Zurich. It \'Jas entitled "Continuous Transcutaneous Monitoring," indicating that not only blood gases but also other parameters could be monitored trans­ cutaneous ly.

This book is the outcome of an international conference, held at the Aviya Sonesta Hotel in Eilat, Israel, on March 24-27, 1985. This was the 30th in a series of the annual OHOLO Conferences, sponsored by the Israel Institute for Biological Research. Participants in this Conference consisted of scientists from four­ teen countries; represented a broad spectrum of research interests; and included a well-balanced representation from academia, clinical institutions and pharmaceutical industry. The book includes talks, poster sessions, and a comprehensive general discussion, all from the proceedings of this conference. In the interest of assuring a rapid publication of the novel infor­ mation reviewed, this book has been prepared in camera-ready format. We are cognizant of the fact that several typographical errors may exist in the text, and that there are variations in style and typeface of the var­ ious chapters. This, we felt, was a reasonable compromise for the sake of speed and efficient transmission of valuable scientific information. No­ body is perfect . •••• The success of the conference, and hence the quality of this book are attributable to the extensive efforts of a large number of extremely capable individuals. These include members of the Scientific Organizing Committee, and the Technical staff of the OHOLO Organization. Of course, the conference could not have succeeded without the high quality of the presentations, and the enthusiastic participation of the contributing scientists.

About a decade ago, psychologists began exploring the commonalities among alcohol and drug abuse, smoking, and obesity. The term sub­ stance abuse evolved into the current concept of addictive behaviors, which recognizes similarities with other behaviors that do not involve consummatory responses (e. g. , pathological gambling, compulsions, sexual deviations). Professional societies and journals now have been founded in both Britain and the United States with the purpose of focus­ ing on research and treatment in the area of addictive behaviors. As the field has evolved, new models have emerged to address the questions and puzzles that face professionals. This volume examines some of these current issues and, in particular, explores common pro­ cesses of change that seem to cut across the addictive behaviors. The chapters are based on papers presented at the Third International Con­ ference on Treatment of Addictive Behaviors, which was held at North Berwick, Scotland, in August of 1984. The conference was organized around an integrative model of stages and processes of change that has been useful in organizing new knowledge about how to intervene with addictive behaviors. This model is set forth by its authors, Jim Prochaska and Carlo DiClemente, in Chapter 1. In Chapter 2, Fred Kanfer ex­ pounds his own model of self-regulation, which overlaps nicely with the Prochaska-DiClemente framework and provides a behavioral-theoretical context.

This volume had its inception at a symposium entitled Aneura1 Organisms: Their Significance for Neurobiology held at the Winter Conference on Brain Research in Vail, Colorado, in January, 1972. The original participants were Drs. Epstein, Hamilton, Kung, Wood and myself. However, since that time several other authors (Drs. Applewhite, Chen, Diehn and Ettienne) were asked to contri­ bute papers and all were asked to update their presentations so as to present a broad perspective as to the role and significance of aneura1 systems for investigating neurobiological problems. This volume is the result of that effort. I wish to thank Dr. Claude F. Baxter, the program chairman of the Winter Conference, and his staff for their help, as well as the contributors for their efforts. Great appreciation is due Mrs. Sharon Loomis for her excellent work in preparing the manuscript for publication. It is our hope that this volume will demonstrate the usefulness and advantages in exploiting aneura1 systems for the insights they may yield in answering some of the fundamental neurobiological questions facing us. E.M. Eisenstein v Contents Aneural Systems and Neurobiology: A Point of View . • . 1 E.M. Eisenstein (Introduction) Protozoa as Models of Stimulus Transduction 5 David C. Wood Genetic Dissection - An Approach to Neurobiology 25 Ching Kung Cybernetics and the Behavior of Microorganisms 41 Bodo Diehn Control of Ciliary Activity in Aneural Organisms 59 Miles Epstein Membrane Potential and Behavior: Proposal of a Model System • . . . . . . . .