1. Postsynaptic histamine H 3 receptors in ventral basal forebrain cholinergic neurons modulate contextual fear memory.
- Author
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Zheng Y, Fan L, Fang Z, Liu Z, Chen J, Zhang X, Wang Y, Zhang Y, Jiang L, Chen Z, and Hu W
- Subjects
- Cholinergic Neurons physiology, Memory physiology, Fear physiology, Histamine, Basal Forebrain
- Abstract
Overly strong fear memories can cause pathological conditions. Histamine H
3 receptor (H3 R) has been viewed as an optimal drug target for CNS disorders, but its role in fear memory remains elusive. We find that a selective deficit of H3 R in cholinergic neurons, but not in glutamatergic neurons, enhances freezing level during contextual fear memory retrieval without affecting cued memory. Consistently, genetically knocking down H3 R or chemogenetically activating cholinergic neurons in the ventral basal forebrain (vBF) mimics this enhanced fear memory, whereas the freezing augmentation is rescued by re-expressing H3 R or chemogenetic inhibition of vBF cholinergic neurons. Spatiotemporal regulation of H3 R by a light-sensitive rhodopsin-H3 R fusion protein suggests that postsynaptic H3 Rs in vBF cholinergic neurons, but not presynaptic H3 Rs of cholinergic projections in the dorsal hippocampus, are responsible for modulating contextual fear memory. Therefore, precise modulation of H3 R in a cell-type- and subcellular-location-specific manner should be explored for pathological fear memory., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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