Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's disease
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-08-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999611830144X |
| _version_ | 1818869967523676160 |
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| author | Alberto Cordella Paraskevi Krashia Annalisa Nobili Annabella Pignataro Livia La Barbera Maria Teresa Viscomi Alessandro Valzania Flavio Keller Martine Ammassari-Teule Nicola Biagio Mercuri Nicola Berretta Marcello D'Amelio |
| author_facet | Alberto Cordella Paraskevi Krashia Annalisa Nobili Annabella Pignataro Livia La Barbera Maria Teresa Viscomi Alessandro Valzania Flavio Keller Martine Ammassari-Teule Nicola Biagio Mercuri Nicola Berretta Marcello D'Amelio |
| author_sort | Alberto Cordella |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T11:59:32Z |
| format | Article |
| id | doaj.art-78ab95f2ced6435c8f675269d247e8a4 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-19T11:59:32Z |
| publishDate | 2018-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-78ab95f2ced6435c8f675269d247e8a42022-12-21T20:22:31ZengElsevierNeurobiology of Disease1095-953X2018-08-01116142154Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's diseaseAlberto Cordella0Paraskevi Krashia1Annalisa Nobili2Annabella Pignataro3Livia La Barbera4Maria Teresa Viscomi5Alessandro Valzania6Flavio Keller7Martine Ammassari-Teule8Nicola Biagio Mercuri9Nicola Berretta10Marcello D'Amelio11Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, Italy; Department of Systems Medicine, University of Rome ‘Tor Vergata’, Rome 00133, ItalyDepartment of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, Italy; Department of Systems Medicine, University of Rome ‘Tor Vergata’, Rome 00133, Italy; Correspondence to: P. Krashia, Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, Italy.Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, Italy; Department of Medicine, University Campus-Biomedico, Rome 00128, ItalyDepartment of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, Italy; Institute of Cell Biology and Neurobiology (IBCN), National Research Council (CNR), Rome 00143, ItalyDepartment of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, Italy; Department of Systems Medicine, University of Rome ‘Tor Vergata’, Rome 00133, ItalyDepartment of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, ItalyDepartment of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, Italy; Department of Psychology and ‘Daniel Bovet’ Centre, Sapienza University, Rome 00185, ItalyDepartment of Medicine, University Campus-Biomedico, Rome 00128, ItalyDepartment of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, Italy; Institute of Cell Biology and Neurobiology (IBCN), National Research Council (CNR), Rome 00143, ItalyDepartment of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, Italy; Department of Systems Medicine, University of Rome ‘Tor Vergata’, Rome 00133, ItalyDepartment of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, Italy; Correspondence to: N. Berretta, Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, Italy.Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome 00143, Italy; Department of Medicine, University Campus-Biomedico, Rome 00128, Italy; Correspondence to: M. D'Amelio, Department of Medicine, University Campus-Biomedico, Rome 00128, Italy.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.http://www.sciencedirect.com/science/article/pii/S096999611830144XAlzheimerTg2576DREADDDopamineVTAHippocampus |
| spellingShingle | Alberto Cordella Paraskevi Krashia Annalisa Nobili Annabella Pignataro Livia La Barbera Maria Teresa Viscomi Alessandro Valzania Flavio Keller Martine Ammassari-Teule Nicola Biagio Mercuri Nicola Berretta Marcello D'Amelio Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's disease Neurobiology of Disease Alzheimer Tg2576 DREADD Dopamine VTA Hippocampus |
| title | Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's disease |
| title_full | Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's disease |
| title_fullStr | Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's disease |
| title_full_unstemmed | Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's disease |
| title_short | Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's disease |
| title_sort | dopamine loss alters the hippocampus nucleus accumbens synaptic transmission in the tg2576 mouse model of alzheimer s disease |
| topic | Alzheimer Tg2576 DREADD Dopamine VTA Hippocampus |
| url | http://www.sciencedirect.com/science/article/pii/S096999611830144X |
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