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

作者：Banks Paul James; Burroughs Amelia Caroline; Barker Gareth Robert Isaac; Brown Jon Thomas; Warburton Elizabeth Clea; Bashir Zafar Iqbal

来源：Proceedings of the National Academy of Sciences, 2015, 112(35): 11096-11101.

DOI：10.1073/pnas.1512064112

• medial prefrontal cortex
• long-term depression
• NMDA receptor hypofunction
• D2R
• schizophrenia

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.

• 出版日期2015-9-1