TY - JOUR
T1 - Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's disease
AU - Cordella, Alberto
AU - Krashia, Paraskevi
AU - Nobili, Annalisa
AU - Pignataro, Annabella
AU - La Barbera, Livia
AU - Viscomi, Maria Teresa
AU - Valzania, Alessandro
AU - Keller, Flavio
AU - Ammassari-Teule, Martine
AU - Mercuri, Nicola Biagio
AU - Berretta, Nicola
AU - D'Amelio, Marcello
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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 rescue the deficits in Tg2576 mice. Our data suggest that the dopaminergic signalling in the hippocampus is essential for the proper functioning of the hippocampus-NAc excitatory synaptic transmission.
AB - 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 rescue the deficits in Tg2576 mice. Our data suggest that the dopaminergic signalling in the hippocampus is essential for the proper functioning of the hippocampus-NAc excitatory synaptic transmission.
KW - Alzheimer
KW - Dopamine
KW - DREADD
KW - Hippocampus
KW - L-DOPA
KW - Memory
KW - Nucleus accumbens
KW - Subiculum
KW - Tg2576
KW - VTA
UR - http://www.scopus.com/inward/record.url?scp=85047375021&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047375021&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2018.05.006
DO - 10.1016/j.nbd.2018.05.006
M3 - Article
AN - SCOPUS:85047375021
VL - 116
SP - 142
EP - 154
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
ER -