Artículos

Alzheimer’s disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and
memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although
dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD
has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic
model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-b (Ab)
oligomers into wild type mice. We found that Ab decreased cortical dopamine levels and converted
in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation
delivered at basolateral amygdaloid nucleuseinsular cortex projection, which led to impaired recognition
memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both highfrequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels
mimicked the Ab-induced shift from LTP to LTD. Our results suggest that Ab-induced dopamine depletion
is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models
and acts by modifying the threshold for the induction of cortical LTP and/or LTD.