New Book on the Biology of Drug Addiction

Drug and alcohol abuse elicits significant biological changes in the brain that drive compulsive behavior and lead to addiction. A new book from CSHL Press, Addiction, reviews the cell and molecular biology of drug addiction. It was edited by R. Christopher Pierce and Paul J. Kenny.

“Our goal was to highlight a cross-section of innovative contemporary addiction research,” write Pierce and Kenny. Contributors explore the biological basis of addiction to alcohol, nicotine, and other psychoactive drugs. They describe the molecular targets of these drugs, the resulting changes to neural networks, and the various genetic, developmental, and behavioral factors that influence the progression from abuse to addiction.

Addiction will be a useful resource for neuroscientists and all who are interested in reducing the public health burden of substance abuse.  For more details on the book, click here.

 

Lab Manual Provides “Gory Detail” for Successful Imaging

Imaging in Neuroscience, the manual from our imaging series that focuses on methods for studying neurons and their circuits, is given a positive review in the current issue of The Quarterly Review of Biology.

 “The most important feature of the manual is the protocol[s] provided,” write Lynne Oland and Patty Jansma. “These are clearly written with the intent of providing the gory detail needed to actually use the protocols successfully, and most chapters include troubleshooting hints, which are most helpful.”

 Oland and Jansma feel that the protocols on glial cells and brain pathology “will make the manual especially useful.” Some of these protocols are available online from Cold Spring Harbor Protocols: For example, check out how to visualize microglia in the mouse cortex, label astrocytes with sulforhodamine 101, and study neural networks in mouse models of Alzheimer’s disease. For more information on the manual, click here.

 

New Book on Parkinson’s Disease

“The shaking palsy,” as it was first described by James Parkinson in 1817, is a disabling neurodegenerative disorder common among the elderly. Parkinson’s Disease, a new book edited by Serge Przedborski, provides a current review of the disease, from its neuropathological and clinical bases to diagnostic challenges and therapeutic interventions.

The book is “designed specifically to bridge the clinical and basic science aspects of Parkinson’s disease under one cover,” writes Przedborski. It will be useful for neurobiologists, cell biologists, and pathologists pursuing the biological basis of Parkinson’s disease, as well as scientists and clinicians interested in its diagnosis and treatment.

Contributors discuss the mutations in genes encoding proteins such as α-synuclein, parkin, and LRRK2 that cause Parkinson’s disease; the roles of mitochondria, autophagy, protein quality control, and programmed cell death in disease progression; and the chemistry and anatomy of the basal ganglia that are affected. The use of functional neuroimaging and experimental models to probe the neurobiology of Parkinson’s disease are also described. For more information, click here.

 

New Book on Synapse Biology

In the mammalian brain, each neuron may receive and extend 10,000 or more synapses, transmitting information that allows an individual to see, move, think, and remember. These structures and how they work are the topic of a new book edited by Morgan Sheng, Bernardo Sabatini, and Thomas Südhof called The Synapse.

“This book tries to capture in a single volume the recent progress and excitement across the breadth of synapse biology,” write the editors. “We have gathered numerous leaders in the study of synapses to write chapters that are both educational and cutting edge.”

Focusing on chemical synapses, the contributors describe the structures of the pre- and post-synaptic regions, trafficking mechanisms that transport vesicles, neurotransmitters and their receptors, and the formation and plasticity of synapses. They also discuss synaptic dysfunction in disorders such as autism and Alzheimer’s disease.

The Synapse will be valuable for neurobiologists, cell and developmental biologists, and anyone wishing to understand how the basic building blocks of the brain are put together and communicate. For more information about the book, click here.

 

Angry Flies

In the wild, aggression is a mechanism for accessing food and shelter, selecting mates, and protecting against predation. Aggressive behavior is shaped by genetics, hormones, experience, and environmental factors, and allows animals to react instinctively to environmental stimuli to enhance their prospects for survival and reproduction.

One of the freely available articles in this month’s issue of Cold Spring Harbor Protocols describes how to score and analyze aggression in Drosophila. Written by Edward Kravitz and Sarah Certel, the protocol explains step-by-step how to construct a fight arena, isolate and paint flies, introduce flies into an arena, and videotape and score fights. One can use this assay as a mutant screen to quantify the effects of genetic lesions in flies, and to unravel the molecular causes and modifiers of aggressive behavior.

Other assays for investigating courtship, sleep, learning and memory, and other behaviors in various organisms are also available from Cold Spring Harbor Protocols. Click here for a list.

 

Methods for Manipulating Synaptic Plasticity

Drosophila Neurobiology: A Laboratory Manual is “an unparalleled resource for the fly neurobiology novice and aficionado” according to a recent review in The Quarterly Review of Biology. Konrad Zinsmaier, the reviewer, described it as an “almost ‘foolproof’ manual” in which each chapter is “well organized, and features a concise introduction, critical references, and detailed experimental protocols.”

One such article, which outlines methods and tools for studying synaptic plasticity in Drosophila, is featured in this month’s issue of Cold Spring Harbor Protocols. The Drosophila larval neuromuscular junction (NMJ) is a well-established model for studying synaptic function; both the motor neurons and the target muscle cells can be directly manipulated at the cellular and molecular levels. In the article, Haig Keshishian provides an overview of experimental genetic methods to manipulate these synaptic connections – including the use of mutated or reengineered ion channels. He also discusses environmental and rearing conditions that phenocopy the genetic approaches that affect synaptic function.

The article is freely accessible from Cold Spring Harbor Protocols here. For more information about Drosophila Neurobiology: A Laboratory Manual, click here.

 

“A Fascinating Adventure in Biomedical Research”

Alzheimer disease insidiously attacks the brain and deprives people of their most human qualities, leading to memory loss, behavior changes, and ultimately, death. An essay in this month’s issue of Cold Spring Harbor Perspectives in Medicine provides an excellent overview of modern Alzheimer research, its origins and development, scope, driving forces, and key questions, as well as competing ideas and findings within the field. It was written by Dennis Selkoe, Eckhard Mandelkow, and David Holtzman, editors of our recent book The Biology of Alzheimer Disease.

In the essay, Selkoe and colleagues outline key developments that followed the first description of the disease by Alois Alzheimer in 1907.  They explain how the discoveries of tau and amyloid β-protein precursor in the late 1980s and early 1990s brought Alzheimer research into sync with basic research in molecular genetics and protein chemistry.  Furthermore, the recognition of Alzheimer disease as a common disorder – currently estimated to affect 20-25 million people worldwide – has helped define it as an urgent problem in biomedical research.

But beyond that, Selkoe and colleagues describe how tackling a complicated disease – and one that affects the most human qualities of memory, reasoning, language, and emotion – can be intellectually rewarding. “The complexity of the problem and the diverse ways in which one might think about approaching it make for a fascinating adventure in biomedical research,” they write.

For more on Alzheimer research – including discussion of competing ideas between “BAPtists” and “TAUists” – read the complete essay here.

 

Tracking Worm Behavior

The colorful scribbles on this month’s cover of Cold Spring Harbor Protocols are tracks from one wild-type worm as it crawls through food on an agar dish.  Such images can reveal movement and behavioral patterns in C. elegans. (If you look closely, you can see evidence of pirouettes and foraging behavior.)

Initial methods to analyze behavioral phenotypes in C. elegans relied on human observation, and were therefore subjective and imprecise. Terms like “sluggish” or “loopy” were used to describe the uncoordinated activity of some mutants. And the procedures were often time-consuming, as the observer was required to monitor worm behavior in real time.

But, as described by Bill Schafer and colleagues in the current issue of Cold Spring Harbor Protocols, automated microscopy and image analysis systems for recording and analyzing worm behavior are much more robust.  They allow for precise quantitative definitions of behavioral phenotypes, and permit the analysis of behaviors that occur over long time periods or are difficult to detect by eye.

In the issue, Schafer and colleagues provide protocols for preparing media and worms for automated tracking and image analysis, describe high-throughput worm behavior analysis using Multiworm Tracker, and offer strategies for obtaining uniform illumination during worm tracking.  They also compare and contrast single- and multi-worm tracking approaches, and describe how comparisons of wild-type and genetically modified worms can be used to functionally dissect the molecular mechanisms behind specific behaviors.

 

New Book on Alzheimer Disease Biology

Understanding the complex changes that occur during Alzheimer disease—including the accumulation of amyloid plaques and neurofibrillary tangles in the brain—is critical for the development of successful therapeutic approaches.  Our newest book, The Biology of Alzheimer Disease, provides a current and comprehensive review of the biological basis of Alzheimer disease (AD).

The editors, Dennis Selkoe, Eckhard Mandelkow, and David Holtzman, chose leading researchers in Alzheimer biology to contribute chapters on topics in which they have deep expertise. The 25 chapters include contributions covering all aspects of Alzheimer disease, from our current molecular understanding of it to therapeutic agents that could be used to treat and prevent it.

Additionally, the first and last chapters provide the editors’ perspectives on the disease, its challenges and prospects for developing effective treatments. “[We] have tried to step back from the wealth of details and convey a sense of what has motivated the global quest to understand the biology of AD, how sometimes competing concepts and lines of inquiry have proceeded, and, most importantly, where we believe this scientifically rich and therapeutically promising field is headed,” they write.

The book is a vital reference for neurobiologists, cell biologists, pathologists, and other scientists pursuing the biological basis of Alzheimer disease, as well as investigators, clinicians, and students interested in its pathogenesis, treatment, and prevention.  For more details, click here.

 

Visualizing Synaptic Connections

The cortex of the mouse brain contains ~4,000,000 neurons, so investigating the complex connectivity of these neurons can be difficult.  Recently, this challenge has been overcome by creating transgenic mice that express fluorescent proteins of different colors in individual neurons in the brain.  In this “Brainbow” approach, Cre/lox recombination is used to randomly express two to four different fluorescent proteins in each neuron. The various combinations of fluorescent proteins can produce neurons of about 100 different colors. As a result, adjacent cells are usually different colors, allowing one to clearly visualize individual cells and their contacts with other cells.

The July issue of Cold Spring Harbor Protocols features an article by Jeff Lichtman, Joshua Sanes, and colleagues, who developed the Brainbow technique.  The article describes currently available Brainbow cassettes and transgenic mice, as well as the elements necessary for creating Brainbow transgenes from scratch.  An accompanying protocol provides step-by-step details for introducing Brainbow transgenes into mice, fixing samples from Brainbow animals, and acquiring and analyzing multichannel images from Brainbow samples.

The cover of the July issue shows motor neurons in the spinal cord of a young adult transgenic Brainbow mouse.  For more on the July issue, click here.