Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents

MAURICIO GERARDO MARTÍN

Workshop; Membrane traffic at the synapse. The cell biology of synaptic plasticity; 2013

Cognitive decline is one of the many characteristics of the aging process. Reduced long-term potentiation (LTP) and long-term depression (LTD) are thought to be responsible for the decline, but we do not precisely know how poor LTP and LTD in the old occur. Electrophysiology recordings in old mice brain slices and in vivo show that the reduced hippocampal LTD and LTP of the old are due to the loss of cholesterol that naturally occurs in this structure during ageing. Mechanistically, cholesterol loss perturbs the normal cellular and molecular responses induced by LTD and LTP, including stimulation-dependent AMPA receptor internalization and lateral diffusion. Functionally, we show here that cholesterol replenishment betters learning and memory in old animals.