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

doi:10.1073/pnas.1512064112

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

Bristol Neuroscience

Research output: Contribution to journal › Article (Academic Journal) › peer-review

32 Citations (Scopus)

788 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 language	English
Pages (from-to)	11096–11101
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	112
Issue number	35
Early online date	15 Aug 2015
DOIs	https://doi.org/10.1073/pnas.1512064112
Publication status	Published - 1 Sept 2015

Keywords

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

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10.1073/pnas.1512064112

PNASSupportingInformationReSubmissionMergedAccepted author manuscript, 4.17 MB
2015 08, Bashir 44352883 (all)Accepted author manuscript, 5.21 MB

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Understanding the hippocampal-perirhinal-prefontal tripartite circuit in associative memory
Bashir, Z. I. (Principal Investigator)
31/03/14 → 29/06/17
Project: Research
CONTRIBUTION OF PREFRONTAL CORTEX TO RECOGNITION MEMORY FUNCTION IN THE RAT
Warburton, E. (Principal Investigator)
1/03/07 → 1/03/10
Project: Research

Professor Zafar I Bashir
- Z.I.Bashirbristol.acuk
- School of Psychology and Neuroscience - Professor of Cellular Neuroscience
- Bristol Neuroscience
Person: Academic , Member
Professor Elizabeth Warburton
- E.C.Warburtonbristol.acuk
- School of Psychology and Neuroscience - Professor of Cognitive Neuroscience, Head of School
- Bristol Neuroscience
Person: Academic , Member

Cite this

Banks, P., Burroughs, A., Barker, G., Brown, J. T., Warburton, C., & Bashir, Z. (2015). Disruption of hippocampal–prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission: NMDARs control hippocampal-PFC synaptic transmission. Proceedings of the National Academy of Sciences of the United States of America, 112(35), 11096–11101. https://doi.org/10.1073/pnas.1512064112

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

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. ",

keywords = "medial prefrontal cortex, long - term depression, NMDA receptor hypofunction, D2R, schizophrenia",

author = "Paul Banks and Amelia Burroughs and Gareth Barker and Brown, \{Jon T\} and Clea Warburton and Zafar Bashir",

year = "2015",

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Banks, P, Burroughs, A, Barker, G, Brown, JT, Warburton, C & Bashir, Z 2015, 'Disruption of hippocampal–prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission: NMDARs control hippocampal-PFC synaptic transmission', Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 35, pp. 11096–11101. https://doi.org/10.1073/pnas.1512064112

Disruption of hippocampal–prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission: NMDARs control hippocampal-PFC synaptic transmission. / Banks, Paul; Burroughs, Amelia; Barker, Gareth et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 35, 01.09.2015, p. 11096–11101.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Disruption of hippocampal–prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission

T2 - NMDARs control hippocampal-PFC synaptic transmission

AU - Banks, Paul

AU - Burroughs, Amelia

AU - Barker, Gareth

AU - Brown, Jon T

AU - Warburton, Clea

AU - Bashir, Zafar

PY - 2015/9/1

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N2 - 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.

AB - 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.

KW - medial prefrontal cortex

KW - long - term depression

KW - NMDA receptor hypofunction

KW - D2R

KW - schizophrenia

U2 - 10.1073/pnas.1512064112

DO - 10.1073/pnas.1512064112

M3 - Article (Academic Journal)

C2 - 26286993

SN - 0027-8424

VL - 112

SP - 11096

EP - 11101

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 35

ER -

Banks P, Burroughs A, Barker G, Brown JT, Warburton C , Bashir Z. Disruption of hippocampal–prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission: NMDARs control hippocampal-PFC synaptic transmission. Proceedings of the National Academy of Sciences of the United States of America. 2015 Sept 1;112(35):11096–11101. Epub 2015 Aug 15. doi: 10.1073/pnas.1512064112

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

Abstract

Keywords

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Projects

Understanding the hippocampal-perirhinal-prefontal tripartite circuit in associative memory

CONTRIBUTION OF PREFRONTAL CORTEX TO RECOGNITION MEMORY FUNCTION IN THE RAT

Profiles

Professor Zafar I Bashir

Professor Elizabeth Warburton

Cite this