The role of astrocyte-neuron interactions in spatial cognition, goal-directed behaviour, and their impairment in Alzheimer’s disease are discussed, and the mouse models used to investigate spatial deficits and associated astrocyte activity are reviewed.
Abstract
Astrocytes sense synaptic activity, neuromodulation, and metabolic signals, and respond by modulating neurotransmission, excitability, and plasticity in neural networks. Increasing evidence demonstrates that these processes contribute to information processing and encoding across brain areas, thereby influencing perception, memory, cognition, and goal-directed behaviours. Notably, impairments in these functions represent some of the earliest hallmarks of ageing and neurodegenerative disorders such as Alzheimer’s disease. Here we review molecular, cellular, and computational insights into astrocyte-neuron interactions, framing their importance at the system and behavioural level; then, we discuss the role of these interactions in spatial cognition, goal-directed behaviour, and their impairment in Alzheimer’s disease, and review the mouse models used to investigate spatial deficits and associated astrocyte activity. Finally, we highlight major open questions in the field, outline future research directions, and discuss emerging strategies to address astrocyte role in cognitive function in health and disease.
Targeting the biochemical modulators of synaptic plasticity offers a promising avenue for AD therapy, especially through combinatorial and precision-medicine strategies aimed at restoring synaptic function and cognitive performance.
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