H2020Индивидуална стипендия2019–2020

GABASSEMBLY · The role of GABAergic circuits in the orchestration of hippocampal neuronal assemblies

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

Период: 2019-01-01 → 2020-12-31
Финансиране от ЕС: 173 076 €
Участници: 1
Схема: MSCA-IF-EF-ST

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Накратко на български

Инхибиторните неврони в хипокампуса на гризачи контролират как се активират групи от клетки при процеси като формирането на паметта. Разбирането на тези механизми помага да се разяснят когнитивните функции и състояния като шизофренията.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

The role of GABAergic circuits in the orchestration of hippocampal neuronal assemblies

A 'cell assembly' is defined as a sparse group of neurons repeatedly activated during a certain mental process. Theoretical and experimental work suggests that the organised activation of cell assemblies underlies cognitive abilities such as memory formation and recall, planning and decision making. The mechanisms leading to the formation, reactivation and disbanding of cell assemblies are still poorly understood. Shedding light on these mechanisms is important for two reasons. First, it could provide crucial information on the neural underpinnings of memory and cognition. Second, it could pave the way to better understand conditions in which cell assembly activity appears altered (in particular neurodevelopmental disorders such as schizophrenia). Inhibitory neurons releasing the neurotransmitter GABA are believed to be fundamental units controlling cell assembly formation and reactivation. Leading theories posit that inhibitory neurons help maintain sparsity (i.e. making sure that only a few neurons are active in a short time window) and help segregate cell assemblies representing different brain operations. However, direct evidence and detailed mechanisms for this theory are still lacking. The rodent hippocampus represents a valuable framework to investigate the role of inhibition in cell assembly activation for various reasons. First, the hippocampus is required for encoding episodic memories. Second, the sequential activation of hippocampal cell assemblies (which are excitatory pyramidal cells) can encode both spatial and temporal information. Third, the inhibitory circuits of the hippocampus are well understood. The aim of the present project was to understand how inhibitory (GABAergic) circuits orchestrate the activation of hippocampal cell assemblies. In the first part of the project, we sought to study the relationship between a special inhibitory subtype ('hub neurons', which are born earliest in development) and cell assemblies. Since the physiological properties and connectivity of these cells was unknown, the aim was also to shed light on these aspects. The second part of the project aimed at studying the spatiotemporal dynamics of inhibition in CA1 region of the hippocampus, at examining the relationship of these dynamics with cell assembly activity and at perturbing inhibitory neurons' activity using optogenetics.

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

Цел на проекта

The last decades of research have revealed that neuronal assemblies are fundamental units of brain computation and cognition. The mechanisms of assembly activity may be clinically relevant, because these cells have been shown to be altered in neuropsychiatric disorders such as schizophrenia and epilepsy. Despite the significance of assemblies, it remains unclear how these cells are orchestrated by GABAergic circuits. Here I propose to investigate the role of GABAergic cells in the activity of hippocampal assemblies using in vivo 2-photon calcium imaging and electrophysiology in awake mice. Thanks to a behavioural paradigm designed in the host laboratory, I will be able to discriminate whether the spatiotemporal patterns of GABAergic activity differ between a hippocampal internal mode (limited and constant sensory inputs) and an external mode (richer and changing sensory inputs). Immunohistochemistry will allow the identification of defined GABAergic classes. Next, I will test whether the activity of GABAergic cells is spatially or temporally correlated with the recruitment of hippocampal cell assemblies. Finally, I will investigate in vivo activity and role in assembly recruitment of a particular population of GABAergic cells. This consists of cells that are born early in development and that at early postnatal age exert a ‘hub’ function, namely they trigger powerful synchronisation of hundreds of cells and of network oscillations. Recent evidence has led to the hypothesis that this GABAergic population may play a critical role in the reactivation of cell assemblies during sleep or quiet wakefulness, a phenomenon that is important for memory consolidation. In summary, this project involves a state-of-the-art multidisciplinary approach at the boundary between cellular and system neuroscience. It may provide unique knowledge on the role of GABAergic cells in network mechanisms that are involved in cognition and that appear pathologically relevant.

Оригинален текст от CORDIS (на английски).

Участници

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisКоординаторФранция