Chronic two-photon microscopy reveals neuronal activity patterns in the cerebral cortex of an Alzheimer's disease mouse model.

Chronic two-photon microscopy is used to investigate neuronal activity patterns in the primary visual cortex of Alzheimer's disease mice (5×FAD). We find that under resting conditions, individual AD neurons exhibit hyperactivity while the neuronal networks show rigid, hypersynchronous connectivity. Following precise optical stimulation of an individual neuron, the network hyperconnectivity is partially reduced. Morphological analysis of dendritic calcium signals reveals that AD neurons exhibit non-specific, widespread calcium propagation upon excitation and significantly increased dendritic length and branching density compared to WT mice, providing a potential link between single-neuron hyperactivity and network-level rigidity. These results demonstrate a hyperactive but rigid network phenotype in AD, providing a circuit-level explanation for early cognitive dysfunction.