Apr 23, 2016

Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment

Neurobiology of Aging
Perla Moreno-CastillaFederico Bermúdez-Rattoni


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-β (Aβ) oligomers into wild type mice. We found that Aβ 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 nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory a...Continue Reading

Mentioned in this Paper

Neuro-Oncological Ventral Antigen 2
Familial Alzheimer Disease (FAD)
In Vivo
Biochemical Pathway
Memory Loss
Tissue Membrane
Adrenal Cortex Diseases
Physiologic Pulse

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