Disruption of hippocampal-prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission.
basic_science · Level V
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- Record sourced from PubMed, PMID 26286993.
- Also identified by DOI 10.1073/pnas.1512064112 and PMC identifier 4568284.
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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.
Medical subject headings
- Hippocampus
- Long-Term Synaptic Depression
- Prefrontal Cortex
- Receptors, N-Methyl-D-Aspartate