Disruption of hippocampal-prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission

被引：32

作者：

Banks, Paul James ^{[1
]}

Burroughs, Amelia Caroline ^{[1
]}

Barker, Gareth Robert Isaac ^{[1
]}

Brown, Jon Thomas ^{[2
]}

Warburton, Elizabeth Clea ^{[1
]}

Bashir, Zafar Iqbal ^{[1
]}

机构：

[1] Univ Bristol, Sch Physiol & Pharmacol, Bristol BS8 1TD, Avon, England

[2] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter EX4 4PS, Devon, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2015年 / 112卷 / 35期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

medial prefrontal cortex; long-term depression; NMDA receptor hypofunction; D2R; schizophrenia; LONG-TERM POTENTIATION; RECEPTOR FUNCTION; SYNAPTIC-TRANSMISSION; ANTIPSYCHOTIC-DRUGS; THETA OSCILLATIONS; BASAL DENDRITES; N-METHYLGLYCINE; FIRING PATTERNS; MODULATION; PLASTICITY;

D O I：

10.1073/pnas.1512064112

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：11096 / 11101

页数：6

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