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DTSTART:20260329T010000
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DTSTART;TZID=Europe/Paris:20261203T140000
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DTSTAMP:20260922T045227
CREATED:20260611T095507Z
LAST-MODIFIED:20260916T094130Z
UID:202997-1796306400-1796306400@www.bordeaux-neurocampus.fr
SUMMARY:Thesis defense - Anaël Erhardt
DESCRIPTION:Venue: Centre Broca \nDefense language: english \n\nAnaël Erhardt\nIINS \nThesis supervisor: Christophe Mulle \nTitle\nPhysiological functions of the amyloid precursor protein (APP) in local circuits within hippocampal CA3 \nAbstract\nThe amyloid precursor protein (APP)\, a key player in Alzheimer’s disease (AD)\, is ubiquitously expressed in a large majority of neurons including both excitatory pyramidal cells (PCs) and GABAergic interneurons (INTs) in the hippocampus. APP is found at the presynapse where it interacts with the vesicle release machinery. In addition\, recent studies have provided evidence of disrupted hippocampal plasticity in conditional APP knockout (KO) of GABAergic forebrain neurons. However\, the physiological role of APP at excitatory synapses and within hippocampal INTs to balance neuronal activity remain largely unknown. Moreover\, local inhibition by specific interneuron subpopulations influences brain rhythms in hippocampal circuits. Here\, I investigated the physiological function of APP\, first at mossy fibers (MFs) to CA3 pyramidal cells (PCs) excitatory synapses\, and second at inhibitory synapses\, in order to define its role in the cellular and circuit activity of the hippocampal CA3 region. By combining ex vivo electrophysiology and proteomic analysis of MF-CA3 synaptosomes\, we highlighted disrupted forms of presynaptic-dependent short-term plasticity associated to a dysregulated presynaptic component\, including identified molecular targets that contribute to the observed phenotype in absence of APP (and of its homolog APLP2 to prevent compensatory mechanisms) at granule cell MFs. Furthermore\, we observed that selective deletion of APP (and APLP2) in CA3 INTs modified the kinetic of spontaneous inhibitory currents in CA3 PCs. Using neuronal morphological reconstruction in addition to electrophysiological characterization we categorized recorded INTs into different clusters\, possibly highlighting INTs subtypes. We noticed subtle significant morpho-functional differences (i.e. cell excitability and dendritic complexity) between control and KO conditions in one specific GABAergic subpopulation. Lastly\, we performed silicon probe in vivo recordings within the CA3 region in awake mice to investigate the potential effects of APP/APLP2 deletion on global circuit activity and cell synchronicity. The exploration of the oscillatory components and spiking activity of putative CA3 PCs and INTs showed unchanged state-dependent firing rates and excitatory population events but revealed alterations of the cross-frequency coupling at given oscillatory frequencies as well as of the synaptic strength specifically between interneuron-interneuron connections. Our work helps to better understand the physiological contribution of APP to the network activity and to excitatory/inhibitory balance within hippocampal circuits\, which are impaired in AD. \n  \nKeywords: amyloid precursor protein\, short-term plasticity\, mossy fibers\, interneurons\, CA3 local circuits\, synaptic integration\, brain oscillations \n  \nJury\nPresident: Jérôme Baufreton \nSpokesperson 1: Silvia Viana Da Silva \nSpokesperson 2: Paola Pousinha \nExaminator: Manuel Valero \nThesis supervisor: Christophe Mulle \n  \n
URL:https://www.bordeaux-neurocampus.fr/en/event/soutenance-de-these-anael-erhardt/
LOCATION:Amphi Centre Broca Nouvelle Aquitaine\, Université de Bordeaux\, 146 Rue Léo Saignat\, Bordeaux\, France\, France
CATEGORIES:Thesis
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