Dopamine D2R is Required for Hippocampal-dependent Memory and Plasticity at the CA3-CA1 Synapse
Autor: | Oskar Ortiz, Patricia García-Sanz, Samuel Alberquilla, Agnès Gruart, José M. Delgado-García, Oscar Solís, Adrián Sanz-Magro, Rosario Moratalla, Isabel Espadas |
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Přispěvatelé: | Ministerio de Ciencia e Innovación (España), Fundación Ramón Areces, European Commission, Ministerio de Sanidad, Servicios Sociales e Igualdad (España), Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Junta de Andalucía |
Rok vydání: | 2020 |
Předmět: |
Male
Cognitive Neuroscience Hippocampus Biology Hippocampal formation memory Mice hippocampal Cellular and Molecular Neuroscience Dopamine receptor D1 Dopamine receptor D2 Avoidance Learning Animals AcademicSubjects/MED00385 RNA Small Interfering CA1 Region Hippocampal long-term potentiation Spatial Memory Mice Knockout Neuronal Plasticity learning AcademicSubjects/SCI01870 Receptors Dopamine D2 Long-term potentiation Drd2−/− CA3 Region Hippocampal Associative learning Mice Inbred C57BL Dopamine receptor Synapses Synaptic plasticity Original Article AcademicSubjects/MED00310 Female Neuroscience |
Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Cerebral Cortex (New York, NY) |
ISSN: | 1460-2199 1047-3211 |
Popis: | Dopamine receptors play an important role in motivational, emotional, and motor responses. In addition, growing evidence suggests a key role of hippocampal dopamine receptors in learning and memory. It is well known that associative learning and synaptic plasticity of CA3-CA1 requires the dopamine D1 receptor (D1R). However, the specific role of the dopamine D2 receptor (D2R) on memory-related neuroplasticity processes is still undefined. Here, by using two models of D2R loss, D2R knockout mice (Drd2-/-) and mice with intrahippocampal injections of Drd2-small interfering RNA (Drd2-siRNA), we aimed to investigate how D2R is involved in learning and memory as well as in long-term potentiation of the hippocampus. Our studies revealed that the genetic inactivation of D2R impaired the spatial memory, associative learning, and the classical conditioning of eyelid responses. Similarly, deletion of D2R reduced the activity-dependent synaptic plasticity in the hippocampal CA1-CA3 synapse. Our results demonstrate the first direct evidence that D2R is essential in behaving mice for trace eye blink conditioning and associated changes in hippocampal synaptic strength. Taken together, these results indicate a key role of D2R in regulating hippocampal plasticity changes and, in consequence, acquisition and consolidation of spatial and associative forms of memory. Spanish Ministries of Science and Innovation (PID2019-111693RBI00, PCIN-2015-098); Ramón Areces Foundation (ref 172275); European Union’s Horizon 2020 research and innovation program, AND-PD (grant agreement no. 848002 to R.M., BFU2017- 82375-R to A.G. and J.M.D.-G.); Health, Social Services and Equality (PI2019/09-3), CIBERNED CB06/05/0055 to R.M.); the Spanish Junta de Andalucía (BIO-122, PY18FR_823 to A.G. and J.M.D.-G.). |
Databáze: | OpenAIRE |
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