Journal article
Cholinergic basal forebrain neurons regulate fear extinction consolidation through p75 neurotrophin receptor signaling
Z Boskovic, MR Milne, L Qian, HD Clifton, AE McGovern, MT Turnbull, SB Mazzone, EJ Coulson
Translational Psychiatry | NATURE PUBLISHING GROUP | Published : 2018
Open access
Abstract
Cholinergic basal forebrain (cBF)-derived neurotransmission plays a crucial role in regulating neuronal function throughout the cortex, yet the mechanisms controlling cholinergic innervation to downstream targets have not been elucidated. Here we report that removing the p75 neurotrophin receptor (p75 NTR ) from cBF neurons induces a significant impairment in fear extinction consolidation. We demonstrate that this is achieved through alterations in synaptic connectivity and functional activity within the medial prefrontal cortex. These deficits revert back to wild-type levels upon re-expression of the active domain of p75 NTR in adult animals. These findings demonstrate a novel role for chol..
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Awarded by University of Queensland
Funding Acknowledgements
This work was supported by the National Health and Medical Research Council of Australia (Project Grant 1049236 to EJC) and the Clem Jones Centre for Aging Dementia Research. Z.B. and MTT were supported by an Australian Postgraduate Awards and a University of Queensland Advantage Scholarship and a Australia Dementia Research Foundation Top-Upscholarship respectively. We thank the staff of the University of Queensland Biological Resources Facility for breeding and maintaining the animals used in this study, members of the Coulson laboratory past and present for helpful discussions and Rowan Tweedale for editorial assistance.