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CORDIS

Interrogating Human Adult Hippocampal Neurogenesis

Project description

Breaking new ground in the field of adult hippocampal neurogenesis

The hippocampus is a brain area critical for learning and memory. Impairment of adult hippocampal neurogenesis is linked to cognitive dysfunction and mood dysregulation in rodents. The hippocampus is particularly vulnerable to damage at the early stages of Alzheimer’s disease. In this context, the ERC-funded HumAN project will shed light on the mechanisms that control the maturation and synaptic integration of newly generated cells in human beings. It will also identify the pathophysiology of neurodegenerative and psychiatric diseases, thereby facilitating the identification of potential novel therapeutic targets for these as yet incurable conditions. The project will determine, for the first time, whether new neurons integrate efficiently into the human hippocampus.

Objective

The hippocampus is crucial for learning and memory and it hosts an extraordinary form of plasticity: the generation of new neurons throughout life, a process named adult hippocampal neurogenesis (AHN). Newly generated neurons grow in a specialised niche composed of unique vascular, glial, and neuronal elements. Impaired AHN leads to cognitive dysfunction and mood dysregulation in rodents. Recent work by my group reveals the persistence of AHN until the tenth decade of human life, as well as impairment of this process in patients with Alzheimer’s disease. The general aim of HumAN is to unveil the features that confer the human hippocampus with neurogenic potential, thoroughly characterising this niche in adulthood, physiological aging, and pathological conditions (AIM 1), and to identify potentially unique AHN signatures for specific neurodegenerative and psychiatric diseases (AIM 2). Moreover, we will determine, for the first time, whether new neurons integrate efficiently into the human hippocampus (AIM 3) and we will interrogate the subcellular machinery of these cells to unravel the mechanisms underlying AHN impairments in these diseases (AIM 4). The unprecedented quality of our collection of human hippocampal samples, obtained from 180 individuals (either controls or with specific neurodegenerative or psychiatric diseases), allows successful application of trail-blazing methodologies such as RNAscope, iterative indirect immunofluorescence imaging (4i)-microscopy, and super-resolution and stimulated emission depleted (STED) nano-resolution microscopy. HumAN will break new ground in the field of AHN by deepening our understanding not only of the mechanisms that control the maturation and synaptic integration of newly generated cells in human beings, but also of the pathophysiology of neurodegenerative and psychiatric diseases, thereby facilitating the identification of potential novel therapeutic targets for these as yet incurable conditions.

Host institution

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Net EU contribution
€ 1 300 458,76
Address
CALLE SERRANO 117
28006 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
Links
Total cost
€ 1 993 792,74

Beneficiaries (2)