biostudies-literatureMaksymetz JBristol-Myers SquibbNICHD NIH HHSNIMH NIH HHSCHDI FoundationNational Institutes of HealthCanadian Institutes for Health ResearchJohnson and JohnsonCIHRDystonia Medical Research FoundationMichael J. Fox FoundationVanderbilt International Scholars ProgramNINDS NIH HHSAstraZenecaSeaside Therapeutics989-1000https://www.ebi.ac.uk/biostudies/studies/S-EPMC6555658biostudies-literatureUnknown85(12)<h4>Background</h4>The prefrontal cortex (PFC) integrates information from multiple inputs to exert top-down control allowing for appropriate responses in a given context. In psychiatric disorders such as posttraumatic stress disorder, PFC hyperactivity is associated with inappropriate fear in safe situations. We previously reported a form of muscarinic acetylcholine receptor (mAChR)-dependent long-term depression in the PFC that we hypothesize is involved in appropriate fear responding and could serve to reduce cortical hyperactivity following stress. However, it is unknown whether this long-term depression occurs at fear-related inputs.<h4>Methods</h4>Using optogenetics with extracellular and whole-cell electrophysiology, we assessed the effect of mAChR activation on the synaptic strengtBiological psychiatryM₁ Muscarinic Receptors Modulate Fear-Related Inputs to the Prefrontal Cortex: Implications for Novel Treatments of Posttraumatic Stress Disorder.PMC6555658U54 HD083211R01 NS069689U19 MH106839R01 MH073676CIHR DFS146189DFS146189R37 NS031373R01 MH062646Moran SPMaksymetz JEngers DWConn PJLindsley CWStansley BJLi BJoffe METemple KLawrence JJfalseM₁ Muscarinic Receptors Modulate Fear-Related Inputs to the Prefrontal Cortex: Implications for Novel Treatments of Posttraumatic Stress Disorder.<h4>Background</h4>The prefrontal cortex (PFC) integrates information from multiple inputs to exert top-down control allowing for appropriate responses in a given context. In psychiatric disorders such as posttraumatic stress disorder, PFC hyperactivity is associated with inappropriate fear in safe situations. We previously reported a form of muscarinic acetylcholine receptor (mAChR)-dependent long-term depression in the PFC that we hypothesize is involved in appropriate fear responding and could serve to reduce cortical hyperactivity following stress. However, it is unknown whether this long-term depression occurs at fear-related inputs.<h4>Methods</h4>Using optogenetics with extracellular and whole-cell electrophysiology, we assessed the effect of mAChR activation on the synaptic strengt2019-01-01T00:00:00Z2019 Jun2026-05-02T09:41:47.76Z2020-06-18T07:01:28ZS-EPMC65556583100378710.1016/j.biopsych.2019.02.020