The Journal of physiology
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The Journal of physiology · Oct 2014
ReviewCholinergic circuit modulation through differential recruitment of neocortical interneuron types during behaviour.
Acetylcholine is a crucial neuromodulator for attention, learning and memory. Release of acetylcholine in primary sensory cortex enhances processing of sensory stimuli, and many in vitro studies have pinpointed cellular mechanisms that could mediate this effect. In contrast, how cholinergic modulation shapes the function of intact circuits during behaviour is only beginning to emerge. ⋯ In contrast to the traditional view of neuromodulation as a relatively slow process, cholinergic signalling can thus rapidly convey time-locked information to neocortex about the behavioural state of the animal and the occurrence of salient sensory stimuli. Importantly, these effects strongly depend on interneuron type, and different interneuron types in turn control distinct aspects of circuit function. One prominent effect of phasic acetylcholine release is disinhibition of pyramidal neurons, which can facilitate sensory processing and associative learning.
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The Journal of physiology · Aug 2014
ReviewTranscranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists.
Two neuromodulatory techniques based on applying direct current (DC) non-invasively through the skin, transcranial cerebellar direct current stimulation (tDCS) and transcutaneous spinal DCS, can induce prolonged functional changes consistent with a direct influence on the human cerebellum and spinal cord. In this article we review the major experimental works on cerebellar tDCS and on spinal tDCS, and their preliminary clinical applications. Cerebellar tDCS modulates cerebellar motor cortical inhibition, gait adaptation, motor behaviour, and cognition (learning, language, memory, attention). ⋯ In the anaesthetised mouse, DC stimulation applied under the skin along the entire spinal cord may affect GABAergic and glutamatergic systems. Preliminary clinical studies in patients with cerebellar disorders, and in animals and patients with spinal cord injuries, have reported beneficial effects. Overall the available data show that cerebellar tDCS and spinal tDCS are two novel approaches for inducing prolonged functional changes and neuroplasticity in the human cerebellum and spinal cord, and both are new tools for experimental and clinical neuroscientists.
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The Journal of physiology · Jul 2014
ReviewThe microbiota-gut-brain axis in gastrointestinal disorders: stressed bugs, stressed brain or both?
The gut-brain axis is the bidirectional communication between the gut and the brain, which occurs through multiple pathways that include hormonal, neural and immune mediators. The signals along this axis can originate in the gut, the brain or both, with the objective of maintaining normal gut function and appropriate behaviour. In recent years, the study of gut microbiota has become one of the most important areas in biomedical research. ⋯ We therefore review the literature on the role of gut microbiota in gut homeostasis and link it with mechanisms that could influence behaviour. We discuss the association of dysbiosis with disease, with particular focus on functional bowel disorders and their relationship to psychological stress. This is of particular interest because exposure to stressors has long been known to increase susceptibility to and severity of gastrointestinal diseases.
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The Journal of physiology · Jun 2014
ReviewChasing Mendel: five questions for personalized medicine.
Ideas about personalized medicine are underpinned in part by evolutionary biology's Modern Synthesis. In this essay we link personalized medicine to the efforts of the early statistical investigators who quantified the heritability of human phenotype and then attempted to reconcile their observations with Mendelian genetics. As information about the heritability of common diseases was obtained, similar efforts were directed at understanding the genetic basis of disease phenotypes. ⋯ In this context, we discuss: (1) the current state of the genotype-phenotype relationship in humans, (2) the common-disease-common-variant hypothesis, (3) the current ability of 'omic' information to inform clinical decision making, (4) emerging ideas about the therapeutic insight available from rare genetic variants, and (5) the social and behavioural barriers to the wider potential success of personalized medicine. There are significant gaps in knowledge as well as conceptual, intellectual, and philosophical limitations in each of these five areas. We then provide specific recommendations to mitigate these limitations and close by asking if it is time for the biomedical research community to 'stop chasing Mendel?'
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Herein, we review mechanisms regulating cerebral blood flow (CBF), with specific focus on humans. We revisit important concepts from the older literature and describe the interaction of various mechanisms of cerebrovascular control. We amalgamate this broad scope of information into a brief review, rather than detailing any one mechanism or area of research. ⋯ With respect to these control mechanisms, we provide evidence against several canonized paradigms of CBF control. Specifically, we corroborate the following four key theses: (1) that cerebral autoregulation does not maintain constant perfusion through a mean arterial pressure range of 60-150 mmHg; (2) that there is important stimulatory synergism and regulatory interdependence of arterial blood gases and blood pressure on CBF regulation; (3) that cerebral autoregulation and cerebrovascular sensitivity to changes in arterial blood gases are not modulated solely at the pial arterioles; and (4) that neurogenic control of the cerebral vasculature is an important player in autoregulatory function and, crucially, acts to buffer surges in perfusion pressure. Finally, we summarize the state of our knowledge with respect to these areas, outline important gaps in the literature and suggest avenues for future research.