Brain and neuroscience advances最新文献

γ-aminobutyric acid has become one of the most widely known neurotransmitter molecules in the brain over the last 50 years, recognised for its pivotal role in inhibiting neural excitability. It emerged from studies of crustacean muscle and neurons before its significance to the mammalian nervous system was appreciated. Now, after five decades of investigation, we know that most neurons are γ-aminobutyric-acid-sensitive, it is a cornerstone of neural physiology and dysfunction to γ-aminobutyric acid signalling is increasingly documented in a range of neurological diseases. In this review, we briefly chart the neurodevelopment of γ-aminobutyric acid and its two major receptor subtypes: the γ-aminobutyric acid_A and γ-aminobutyric acid_B receptors, starting from the humble invertebrate origins of being an 'interesting molecule' acting at a single γ-aminobutyric acid receptor type, to one of the brain's most important neurochemical components and vital drug targets for major therapeutic classes of drugs. We document the period of molecular cloning and the explosive influence this had on the field of neuroscience and pharmacology up to the present day and the production of atomic γ-aminobutyric acid_A and γ-aminobutyric acid_B receptor structures. γ-Aminobutyric acid is no longer a humble molecule but the instigator of rich and powerful signalling processes that are absolutely vital for healthy brain function.

Ethanol is a psychoactive substance causing both short- and long-term behavioural changes in humans and animal models. We have used the fruit fly Drosophila melanogaster to investigate the effect of ethanol exposure on the expression of the Gαq protein subunit. Repetitive exposure to ethanol causes a reduction in sensitivity (tolerance) to ethanol, which we have measured as the time for 50% of a set of flies to become sedated after exposure to ethanol (ST50). We demonstrate that the same treatment that induces an increase in ST50 over consecutive days (tolerance) also causes a decrease in Gαq protein subunit expression at both the messenger RNA and protein level. To identify whether there may be a causal relationship between these two outcomes, we have developed strains of flies in which Gαq messenger RNA expression is suppressed in a time- and tissue-specific manner. In these flies, the sensitivity to ethanol and the development of tolerance are altered. This work further supports the value of Drosophila as a model to dissect the molecular mechanisms of the behavioural response to alcohol and identifies G proteins as potentially important regulatory targets for alcohol use disorders.

Neuropsychiatric disorders are complex conditions with poorly defined neurobiological bases. In recent years, there have been significant advances in our understanding of the genetic architecture of these conditions and the genetic loci involved. This review article describes historical attempts to identify susceptibility genes for neuropsychiatric disorders, recent progress through genome-wide association studies, copy number variation analyses and exome sequencing, and how these insights can inform the neuroscientific investigation of these conditions.

In this article, we describe our involvement in the early days of research into long-term potentiation. We start with a description of the early experiments conducted in Oslo and London where long-term potentiation was first characterised. We discuss the ways in which the molecular pharmacology of glutamate receptors control the induction and expression of long-term potentiation and its counterpart, long-term depression. We then go on to summarise the extraordinary advances in understanding the cellular mechanisms of synaptic plasticity that have taken place in the subsequent half century. Finally, the increasing evidence that impaired long-term potentiation is a core feature of many brain disorders (LToPathies) is addressed by way of a few selected examples.

Although most people are right-handed and have language in their left cerebral hemisphere, why that is so, and in particular why about ten per cent of people are left-handed, is far from clear. Multiple theories have been proposed, often with little in the way of empirical support, and sometimes indeed with strong evidence against them, and yet despite that have become modern urban myths, probably due to the symbolic power of right and left. One thinks in particular of ideas of being right-brained or left-brained, of suggestions that left-handedness is due to perinatal brain damage, of claims that left-handers die seven years earlier than right-handers, and of the unfalsifiable ramifications of the byzantine Geschwind-Behan-Galaburda theory. This article looks back over the past fifty years of research on brain asymmetries, exploring the different themes and approaches, sometimes in relation to the author's own work. Taking all of the work together it is probable that cerebral asymmetries are under genetic control, probably with multiple genetic loci, only a few of which are now beginning to be found thanks to very large databases that are becoming available. Other progress is also seen in proper meta-analyses, the use of fMRI for studying multiple functional lateralisations in large number of individuals, fetal ultra-sound for assessing handedness before birth, and fascinating studies of lateralisation in an ever widening range of animal species. With luck the next fifty years will make more progress and show fewer false directions than had much of the work in the previous fifty years.

This review provides a distillate of the advances in knowledge about the neurotransmitter functions of acetylcholine over the 50-year period between 1967 and 2017, together with incremental information about the cognate nicotinic and muscarinic acetylcholine receptors, and some brief comments on possible advances in the near future. The text is supplemented by a timelines figure indicating the dates of some key advances in knowledge about acetylcholine receptors and a box-figure providing a snapshot of selected papers about acetylcholine published in the year 1967.