Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's disease

Neurobiology of Disease
Alberto CordellaMarcello D'Amelio

Abstract

The functional loop involving the ventral tegmental area (VTA), dorsal hippocampus and nucleus accumbens (NAc) plays a pivotal role in the formation of spatial memory and persistent memory traces. In particular, the dopaminergic innervation from the VTA to the hippocampus is critical for hippocampal-related memory function and alterations in the midbrain dopaminergic system are frequently reported in Alzheimer's disease (AD), contributing to age-related decline in memory and non-cognitive functions. However, much less is known about the hippocampus-NAc connectivity in AD. Here, we evaluated the functioning of the hippocampus-to-NAc core connectivity in the Tg2576 mouse model of AD that shows a selective and progressive degeneration of VTA dopaminergic neurons. We show that reduced dopaminergic innervation in the Tg2576 hippocampus results in reduced synaptic plasticity and excitability of dorsal subiculum pyramidal neurons. Importantly, the glutamatergic transmission from the hippocampus to the NAc core is also impaired. Chemogenetic depolarisation of Tg2576 subicular pyramidal neurons with an excitatory Designer Receptor Exclusively Activated by Designer Drugs, or systemic administration of the DA precursor levodopa, can both ...Continue Reading

Citations

Sep 4, 2019·Nature Communications·Paraskevi KrashiaNicola Biagio Mercuri
Jun 18, 2020·Brain Sciences·Gloria Ortiz-GuerreroMauricio O Nava-Mesa
Aug 17, 2020·Journal of Neurochemistry·David C ConsoliFiona E Harrison
Apr 10, 2019·Current Alzheimer Research·Eunice D Farfán-GarcíaMarvin A Soriano-Ursúa
Jun 4, 2019·Frontiers in Molecular Neuroscience·Paraskevi KrashiaMarcello D'Amelio
Jan 27, 2021·Neuroscience and Biobehavioral Reviews·Francesco Fornai, Stefano Puglisi-Allegra
May 1, 2021·Journal of Clinical Medicine·Ágoston PatthyAlán Alpár
Jul 3, 2021·International Journal of Molecular Sciences·Jaydeep RoyLee Wei Lim
Aug 13, 2021·Neural Regeneration Research·Yaojun Ju, Kin Yip Tam
Nov 14, 2021·Alzheimer's Research & Therapy·Arianna SalaDaniela Perani

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