Disruption of hippocampal-prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission.
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.
School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, United Kingdom;
Paul James
PJ
Banks
School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, United Kingdom;
Amelia Caroline
AC
Burroughs
School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, United Kingdom;
Gareth Robert Isaac
GR
Barker
Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, EX4 4PS, United Kingdom.
Jon Thomas
JT
Brown
School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, United Kingdom;
Elizabeth Clea
EC
Warburton
School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, United Kingdom; Z.I.Bashir@bristol.ac.uk.
Zafar Iqbal
ZI
Bashir
D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D009435:Synaptic Transmission
D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate
D2R; NMDA receptor hypofunction; long-term depression; medial prefrontal cortex; schizophrenia