Abstract
Alzheimer’s disease is associated with altered neuronal activity, presumably due to impairments in homeostatic synaptic plasticity. Neuronal hyper and hypoactivity are also observed in mouse models of amyloid pathology. Using multicolor two-photon microscopy, we test how amyloid pathology alters the structural dynamics of excitatory and inhibitory synapses and their homeostatic adaptation to altered experience-evoked activity in vivo in a mouse model. The baseline dynamics of mature excitatory synapses and their adaptation to visual deprivation are not altered in amyloidosis. Likewise, the baseline dynamics of inhibitory synapses are not affected. In contrast, despite unaltered neuronal activity patterns, amyloid pathology leads to a selective disruption of homeostatic structural disinhibition on the dendritic shaft. We show that excitatory and inhibitory synapse loss is locally clustered under the nonpathological state, but amyloid pathology disrupts it, indicating impaired communication of changes in excitability to inhibitory synapses.
Competing Interest Statement
The authors have declared no competing interest.
