Disruption of hippocampal–prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission: NMDARs control hippocampal-PFC synaptic transmission

Paul Banks, Amelia Burroughs, Gareth Barker, Jon T Brown, Clea Warburton, Zafar Bashir

Research output: Contribution to journalArticle (Academic Journal)

16 Citations (Scopus)
522 Downloads (Pure)

Abstract

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.
Original languageEnglish
Pages (from-to)11096–11101
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number35
Early online date15 Aug 2015
DOIs
Publication statusPublished - 1 Sep 2015

Keywords

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

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