1. Cholinergic basal forebrain neurons regulate fear extinction consolidation through p75 neurotrophin receptor signaling.
- Author
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Boskovic Z, Milne MR, Qian L, Clifton HD, McGovern AE, Turnbull MT, Mazzone SB, and Coulson EJ
- Subjects
- Animals, Axons, Female, Male, Mice, Knockout, Neural Pathways cytology, Neural Pathways metabolism, Prefrontal Cortex cytology, Prefrontal Cortex metabolism, Basal Forebrain cytology, Basal Forebrain metabolism, Cholinergic Neurons cytology, Cholinergic Neurons metabolism, Extinction, Psychological physiology, Fear physiology, Memory Consolidation physiology, Receptors, Nerve Growth Factor metabolism
- 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 p75NTR in adult animals. These findings demonstrate a novel role for cholinergic neurons in fear extinction consolidation and suggest that neurotrophic signaling is a key regulator of cholinergic-cortical innervation and function.- Published
- 2018
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