Delineation of experience-dependent astrocyte-neuron cognitive dynamics

Informations projet

ANCoDy

N° de convention de subvention: 101064009

DOI

10.3030/101064009

Projet clôturé

Date de signature de la CE 13 Juin 2022

Date de début 1 Septembre 2022

Date de fin 31 Août 2024

Financé au titre de

• Marie Skłodowska-Curie Actions (MSCA)

Coût total

Aucune donnée

Contribution de l’UE

€ 230 774,40

Coordonné par

KOBENHAVNS UNIVERSITET
Denmark

Periodic Reporting for period 1 - ANCoDy (Delineation of experience-dependent astrocyte-neuron cognitive dynamics)

Période du rapport: 2022-09-01 au 2024-08-31

Résumé du contexte et des objectifs généraux du projet

ANCoDy (Astro-Neu Cognitive Dynamics) is driven by the growing recognition that astrocytes, a type of brain cell traditionally seen as "support cells," play a much more active role in brain function. While astrocytes were once believed to only provide structural support for neurons, recent research shows that they are involved in critical processes such as learning, memory, and cognitive functions. However, the exact way in which astrocytes and neurons interact to support these functions is still not fully understood. This is particularly important because abnormalities in astrocytes have been linked to major neurological disorders like Alzheimer’s Disease.
ANCoDy sets out to test the hypothesis that astrocyte-neuron interactions are shaped by experiences and these are crucial for learning and memory. I used cutting-edge genetic and imaging techniques in mice to observe how astrocytes and neuronal activity changes in the brain during learning tasks. The project focuses on three key objectives:
1. Determine the fundamental properties of astrocyte-neuron interactions that change with learning experiences.
2. Establish a causal link between astrocyte-neuron activity and learning by manipulating astrocyte activity and observing the effects on brain function and behaviour.
3. Define the role of astrocytes in computations that support learning and memory, using advanced statistical models and machine learning techniques to analyse the data.
Pathway to Impact
ANCoDy’s results are expected to deepen our understanding of how astrocyte-neuron interactions influence cognition, addressing a significant gap in brain research. By revealing the role of astrocytes in learning and memory, the project could inspire new therapeutic approaches for conditions like Alzheimer’s Disease.
In addition, ANCoDy’s development of new computational tools will benefit the broader neuroscience community, aiding researchers in exploring brain cell interactions. Given that astrocytes make up over 50% of brain cells, understanding their role could have a profound impact on brain science and the treatment of cognitive disorders. ANCoDy aims to transform how we view brain function and open up new possibilities for therapeutic interventions.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

ANCoDy focused on exploring the role of astrocyte-neuron interactions in learning and memory. Key activities included the collection of over 18 TB of data using two-photon microscopy to observe astrocyte and neuron calcium dynamics in the visual cortex of mice during a learning task. Due to a series of delays, the task was modified to a spontaneous perceptual learning task, and data were successfully collected from 32 mice.
Further activities involved the use of IP3R2 knockout mice to study the impact of reduced astrocytic calcium signalling on learning. Data from 12 knockout and 12 control mice were collected, and analysis is ongoing to establish the link between astrocytic activity and learning performance.
In parallel, advanced statistical and computational models are being developed in collaboration with experts to analyse the complex datasets. Preliminary results have been presented at international conferences, highlighting early insights into the role of astrocytes in brain computation. These findings contribute to the project’s objective of uncovering the significance of astrocyte-neuron dynamics in cognitive processes, with ongoing work expected to provide further breakthroughs.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

ANCoDy has made significant strides in uncovering the role of astrocyte-neuron interactions in learning and memory. Key results include the successful collection of a large dataset using two-photon microscopy to track calcium dynamics in astrocytes and neurons during a spontaneous perceptual learning task. Preliminary analyses have shown early insights into how these cells communicate during learning, with data from both control and IP3R2 knockout mice suggesting that astrocytic activity plays a crucial role in regulating cognitive functions.
Advanced computational models are being fitted with this dataset to explore the precise mechanisms of astrocyte-neuron communication. These results are expected to deepen our understanding of how astrocytes contribute to brain computation and could reshape our understanding of learning and memory processes.
In terms of potential impacts, the project holds promise for future therapeutic applications, particularly in treating neurological conditions like Alzheimer’s Disease, where cognitive decline is prominent. However, further research is needed to fully exploit the findings. Ongoing analysis of the dataset and additional experiments will be crucial to validate the results and determine their broader implications.
Key needs for the success and uptake of ANCoDy’s outcomes include continued collaboration with computational and experimental neuroscientists, further refinement of the data analysis, and potential follow-up studies to translate these insights into therapeutic strategies for brain disorders.