I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

The Cationminus signpi Interaction.

An overview of the self-organizing map algorithm, on which the papers in this issue are based, is presented in this article.

The Self-Organizing Map

Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodeling, and the localization of atherosclerotic lesions. Major regulation of the blood vessel responses occurs by the action of hemodynamic shear stresses on the endothelium. The transmission of hemodynamic forces throughout the endothelium and the mechanotransduction mechanisms that lead to biophysical, biochemical, and gene regulatory responses of endothelial cells to hemodynamic shear stresses are reviewed.

/pdf/flow-mediated-endothelial-mechanotransduction-281f54bq52.pdf

Flow-mediated endothelial mechanotransduction

Recent studies have begun to characterize the actions of stress and antidepressant treatments beyond the neurotransmitter and receptor level. This work has demonstrated that long-term antidepressant treatments result in the sustained activation of the cyclic adenosine 3',5'-monophosphate system in specific brain regions, including the increased function and expression of the transcription factor cyclic adenosine monophosphate response element-binding protein. The activated cyclic adenosine 3',5'-monophosphate system leads to the regulation of specific target genes, including the increased expression of brain-derived neurotrophic factor in certain populations of neurons in the hippocampus and cerebral cortex. The importance of these changes is highlighted by the discovery that stress can decrease the expression of brain-derived neurotrophic factor and lead to atrophy of these same populations of stress-vulnerable hippocampal neurons. The possibility that the decreased size and impaired function of these neurons may be involved in depression is supported by recent clinical imaging studies, which demonstrate a decreased volume of certain brain structures. These findings constitute the framework for an updated molecular and cellular hypothesis of depression, which posits that stress-induced vulnerability and the therapeutic action of antidepressant treatments occur via intracellular mechanisms that decrease or increase, respectively, neurotrophic factors necessary for the survival and function of particular neurons. This hypothesis also explains how stress and other types of neuronal insult can lead to depression in vulnerable individuals and it outlines novel targets for the rational design of fundamentally new therapeutic agents.

A molecular and cellular theory of depression

Lipid rafts — specialized plasma membrane microdomains that are thought to regulate various signalling events — are the focus of intensive research into their roles in the nervous system. Here, Rasenick and colleagues review the evidence for their involvement in regulating neurotransmitter signalling. Lipid rafts are specialized structures on the plasma membrane that have an altered lipid composition as well as links to the cytoskeleton. It has been proposed that these structures are membrane domains in which neurotransmitter signalling might occur through a clustering of receptors and components of receptor-activated signalling cascades. The localization of these proteins in lipid rafts, which is affected by the cytoskeleton, also influences the potency and efficacy of neurotransmitter receptors and transporters. The effect of lipid rafts on neurotransmitter signalling has also been implicated in neurological and psychiatric diseases.

Lipid raft microdomains and neurotransmitter signalling

Tubulin binds specifically to the signal-transducing proteins, Gs alpha and Gi alpha 1.

Heterotrimeric GTP-binding regulatory proteins (G proteins) have been identified as part of signal transduction systems in a wide variety of organisms. In this paper, we establish the presence of a G protein associated with the plasma membranes of the apical bud of etiolated peas. The GTPase activity is induced by low fluences of blue light administered to plasma membrane-enriched fractions. The activity is not responsive to red-light irradiation and is specific for GTP. The threshold for the excitation of the GTPase activity in vitro is less than 10(-1) mumol.m-2 of blue light, consistent with participation in the blue low-fluence system identified in the same tissue. A 40-kDa polypeptide is recognized by polyclonal antisera directed against the alpha subunit of the G protein transducin. The polypeptide also serves as a substrate for ADP-ribosylation by cholera and pertussis toxins. The ability of the 40-kDa polypeptide to serve as substrate for the toxin-mediated ribosylation is mediated by blue-light irradiation, implying that the 40-kDa polypeptide is the alpha subunit of a blue-light-stimulated G protein. The 40-kDa polypeptide binds a nonhydrolyzable photoaffinity-labeling analog of GTP only after irradiation with blue light. The protein we have described may function as an alpha subunit of a G protein active in the process of light-mediated development in higher plants.

https://www.pnas.org/content/pnas/88/20/8925.full.pdf

A blue-light-activated GTP-binding protein in the plasma membranes of etiolated peas.

Activation of adenylate cyclase by a stable guanosine 5'-triphosphate analog was augmented in brain membrane preparations from rats treated on a long-term basis with tricyclic antidepressants or electroconvulsive shock. These treatments may facilitate cyclase activation by promoting the interaction of the regulatory and catalytic subunits of the enzyme. This finding suggests a possible mechanism for the changes in sensitivity to various neurotransmitters seen after antidepressant administration.

http://science.sciencemag.org/content/sci/219/4580/65.full.pdf

Guanosine triphosphate activation of brain adenylate cyclase: enhancement by long-term antidepressant treatment.

The adenylate cyclase system, which mediates cellular responses to a variety of hormones and neurotransmitters, contains at least three plasma membrane-associated proteins: the hormone receptor, the regulatory or guanyl nucleotide-binding unit (G unit) and the catalytic moiety. Activation of the enzyme after binding of hormone to the receptor involves binding of GTP to the G unit1. Activation can be enhanced by increasing the fluidity of the membrane with unsaturated fatty acids2 with the local anaesthetic prilocaine3, and perhaps, in vivo, by phospholipid methylation4. Disruption of microtubules increases localized mobility of membrane proteins in a manner similar to that of unsaturated fatty acids5 and can enhance cyclic AMP accumulation in intact leukocytes6–9. We therefore decided to investigate whether there is a direct interaction between micro-tubules and adenylate cyclase. We show here that colchicine, vinblastine and cis- unsaturated fatty acids enhance G unit-mediated activation of adenylate cyclase, implying that microtubules or tubulin are involved in the attachment of the G unit to the membrane.

Mark M. Rasenick

Papers

Lipid raft microdomains and neurotransmitter signalling

Tubulin binds specifically to the signal-transducing proteins, Gs alpha and Gi alpha 1.

A blue-light-activated GTP-binding protein in the plasma membranes of etiolated peas.

Guanosine triphosphate activation of brain adenylate cyclase: enhancement by long-term antidepressant treatment.

The regulatory subunit of adenylate cyclase interacts with cytoskeletal components