期刊
CEREBRAL CORTEX
卷 31, 期 4, 页码 2187-2204出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhaa354
关键词
Drd2(-/-); hippocampal; learning; long-term potentiation; memory
资金
- Spanish Ministries of Science and Innovation [PID2019-111693RB-I00, PCIN-2015-098]
- Ramon Areces Foundation [172275]
- European Union [848002, BFU2017-82375-R]
- Health, Social Services and Equality [PI2019/09-3, CIBERNED CB06/05/0055]
- Spanish Junta de Andalucia [BIO-122, PY18FR_823]
The genetic inactivation of D2R impairs spatial memory, associative learning, and classical conditioning of eyelid responses, as well as reduces activity-dependent synaptic plasticity in the hippocampal CA1-CA3 synapse. These findings demonstrate the key role of D2R in regulating hippocampal plasticity changes and affecting the acquisition and consolidation of spatial and associative forms of memory.
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 D-1 receptor (D1R). However, the specific role of the dopamine D-2 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.
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