期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 35, 页码 11096-11101出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1512064112
关键词
medial prefrontal cortex; long-term depression; NMDA receptor hypofunction; D2R; schizophrenia
资金
- Wellcome Trust [087855/z/08/z]
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/L001896/1]
- BBSRC [BB/L001896/1, BB/E010407/1] Funding Source: UKRI
- Alzheimers Research UK [ARUK-SRF2012-6] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council [BB/L001896/1, BB/E010407/1] Funding Source: researchfish
- Wellcome Trust [087855/Z/08/Z] Funding Source: Wellcome Trust
Functional connectivity between the hippocampus and prefrontal cortex (PFC) is essential for associative recognition memory and working memory. Disruption of hippocampal-PFC synchrony occurs in schizophrenia, which is characterized by hypofunction of NMDA receptor (NMDAR)-mediated transmission. We demonstrate that activity of dopamine D2-like receptors (D2Rs) leads selectively to long-term depression (LTD) of hippocampal-PFC NMDAR-mediated synaptic transmission. We show that dopamine-dependent LTD of NMDAR-mediated transmission profoundly disrupts normal synaptic transmission between hippocampus and PFC. These results show how dopaminergic activation induces long-term hypofunction of NMDARs, which can contribute to disordered functional connectivity, a characteristic that is a hallmark of psychiatric disorders such as schizophrenia.
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