Investigating neuron-astrocyte interaction in spatial memory and its loss in AD

The ability to learn new spatial memories is thought to depend on the plasticity of neural circuits in the hippocampus, whose progressive degradation in Alzheimer’s disease (AD) leads to severe cognitive impairments. While decades of in vitro studies indicate that astrocytes regulate various forms of neuronal synaptic plasticity, how the interplay between hippocampal astrocytes and neurons underlies spatial memory in vivo remains unknown, as does its potential link to AD's pathogenesis.To address these challenges, we developed a spatial memory task where mice, tracked with DeepLabCut automated videography, learn to forage for food hidden at three reward locations. These locations are changed every day and relearned during 40 trials. After the learning trials, we tested the mice's short- or long-term memory by measuring the time spent exploring empty reward locations on the same day and the following day, before new locations are introduced.We trained cohorts of 3, 6 and 8 months-old wild-type mice, and compared them to an age-matched mouse model of AD. All mice easily learnt the task and showed robust short-term memory. However, AD mice struggled to remember reward locations from the previous day, a long-term memory deficit which worsened from 6 to 8 months of age.These results demonstrate that our behavioural paradigm can be used to investigate the cellular correlates of spatial learning and its progressive decline in an AD mouse model. To identify these correlates, we are currently combining this assay with functional imaging of neuronal and astrocytic hippocampal populations.