H2020Индивидуална стипендия2016–2018

LSD-CortLVPC · Applying voltage-imaging techniques to visualise the effect of lysergic acid diethylamide (LSD) on cortical layer V pyramidal cells and its adaptation during tolerance development

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2016-06-01 → 2018-05-31
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Влиянието на LSD върху пирамидалните клетки в мозъка и кръвотока се проследява чрез специални техники за визуализиране при мишки. Това помага да се разбере как точно работят халюциногените и как влияят на човешкото здраве и съзнание.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Applying voltage-imaging techniques to visualise the effect of lysergic acid diethylamide (LSD) on cortical layer V pyramidal cells and its adaptation during tolerance development

Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD), are psychoactive drugs which induce profound alterations of consciousness. They are popular drugs of abuse, but most recently also re-gained attention as possible promotors of psychotherapy. The controversy surrounding these drugs remains unresolved by modern science and politics, and demands for a strong scientific basis able to reveal how these drugs work and how their working potentially translates into benefit and/or detriment to human health and society. Serotonergic hallucinogens interact with a variety of different monoamine receptors (proteins that govern the communication patterns across neurons), yet their psychoactive effects are thought to be primarily mediated by serotonin (5-HT) 2A receptors. 5-HT2A receptors densely populate certain neurons within the cortex of the brain (particularly influencing so called pyramidal cells), but they can also be found widely across the vascular system. How neuronal and vascular 5-HT2A receptors orchestrate to give rise to the brain dynamics characteristic for these drugs, however, is still largely unknown. That most serotonergic hallucinogens (including LSD) tend to be highly promiscuous in their receptor binding preferences, adds another layer of complexity and renders any final appraisal of the mechanistic implications of 5-HT2A receptors difficult. Here, taking advantage of a recent development in drug design, we use the highly selective 5-HT2(A) agonist 25CN-NBOH in mice. We describe the drug as to the essentials of its behavioural and autonomic properties; apply pulse oximetry to measure drug induced blood flow changes in brain-imminent arteries; and follow up on peripyramidal haemodynamics and midlayer pyramidal cell activity by means of cutting-edge techniques of optogenetic brain imaging. The overall aim is to provide insights into the (neuro-)physiology of 5-HT2A activity, delineating a possible mechanism of action of serotonergic hallucinogens.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Serotonergic hallucinogens (sHG), such as lysergic acid diethylamide (LSD), rank among the most controversially discussed agents of modern neuropsychopharmacology. They are popular drugs of abuse, scientifically are used to study the pathophysiology of psychosis, can pose a threat to health, but most recently also re-gained attention as promotors of psychotherapy. The controversy at hand remains unresolved by modern science and politics, and the European Research Area is faced with the imminent challenge to come up with a strong and competitive scientific basis that is able to elucidate how these drugs work and how their working potentially translates into benefit and/or detriment to European health and society. The psychoactive effects of sHG are mediated by activation of serotonin 2A (5-HT2A) receptors within the cortex of the brain. In vivo, sHG disconnect cortical networks, desynchronise alpha oscillations and inhibit the metabolism of the cortex. In vitro, sHG primarily enhance the excitability of cortical layer V pyramidal cells (LVPCs), which is accounted for by 5-HT2A-glutamate interaction. The in vivo effects of sHG often are interpreted with regard to their in vitro effects. As there are virtually no LVPC specific investigations in living animals, however, the in vivo relevance of the postulated 5-HT2A-LVPC-glutamate triangle is highly speculative. Our project brings together Prof. Thomas Knöpfel, who has been pioneering optogenetic electrophysiology, and the 5-HT2A-hallucinogen expertise of Dipl. Psych. Tobias Buchborn. It applies advanced techniques of voltage imaging (with the voltage-sensitive fluorescent protein Butterfly 1.2 genetically targeted to LVPCs), combines them with selective neuropharmacological challenges and 5-HT2A specific ethological observations, and reveals within the brain of waking mice whether it is indeed LVPCs and their submissiveness to 5-HT2A-glutamate interaction that represent the point pivot of the cortical action of LSD.

Оригинален текст от CORDIS (на английски).

Участници

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE · LondonКоординаторОбединеното кралство