Presenilin 1 regulates homeostatic synaptic scaling through Akt signaling.

Neurons adapt to long-lasting changes in network activity, both in vivo and in vitro, by adjusting their synaptic strengths to stabilize firing rates. We found that homeostatic scaling of excitatory synapses was impaired in hippocampal neurons derived from mice lacking presenilin 1 (Psen1(-/-) mice) or expressing a familial Alzheimer's disease-linked Psen1 mutation (Psen1(M146V)). These findings suggest that deficits in synaptic homeostasis may contribute to brain dysfunction in Alzheimer's disease.