ProBDNF Dependence of LTD and Fear Extinction Learning in the Amygdala of Adult Mice
- 1 September 2021
- journal article
- research article
- Published by Oxford University Press (OUP) in Cerebral Cortex
- Vol. 32 (7), 1350-1364
- https://doi.org/10.1093/cercor/bhab265
Abstract
Neurotrophins are secreted proteins that control survival, differentiation, and synaptic plasticity. While mature neurotrophins regulate these functions via tyrosine kinase signaling (Trk), uncleaved pro-neurotrophins bind preferentially to the p75 neurotrophin receptor (p75NTR) and often exert opposite effects to those of mature neurotrophins. In the amygdala, brain-derived neurotrophic factor (BDNF) enables long-term potentiation as well as fear and fear extinction learning. In the present study, we focused on the impact of mature BDNF and proBDNF signaling on long-term depression (LTD) in the lateral amygdala (LA). Hence, we conducted extracellular field potential recordings in an in vitro slice preparation and recorded LTD in cortical and thalamic afferents to the LA. LTD was unchanged by acute block of BDNF/TrkB signaling. In contrast, LTD was inhibited by blocking p75NTR signaling, by disinhibition of the proteolytic cleavage of proBDNF into mature BDNF, and by preincubation with a function-blocking anti-proBDNF antibody. Since LTD-like processes in the amygdala are supposed to be related to fear extinction learning, we locally inhibited p75NTR signaling in the amygdala during or after fear extinction training, resulting in impaired fear extinction memory. Overall, these results suggest that in the amygdala proBDNF/p75NTR signaling plays a pivotal role in LTD and fear extinction learning.Funding Information
- European Regional Development Fund (ZS/2016/04/78123)
- Horizon 2020 (643417)
- Deutsche Forschungsgemeinschaft (TP B6, SFB 779)
This publication has 103 references indexed in Scilit:
- Propofol Neurotoxicity Is Mediated by p75 Neurotrophin Receptor ActivationAnesthesiology, 2012
- Prenatal stress alters hippocampal synaptic plasticity in young rat offspring through preventing the proteolytic conversion of pro‐brain‐derived neurotrophic factor (BDNF) to mature BDNFJournal Of Physiology-London, 2012
- Coactivation of thalamic and cortical pathways induces input timing–dependent plasticity in amygdalaNature Neuroscience, 2011
- Postsynaptic BDNF‐TrkB signaling in synapse maturation, plasticity, and diseaseDevelopmental Neurobiology, 2010
- Chronic nicotine exposure induces a long-lasting and pathway-specific facilitation of LTP in the amygdalaLearning & Memory, 2008
- Amygdala depotentiation and fear extinctionProceedings of the National Academy of Sciences of the United States of America, 2007
- Low-frequency stimulation induces a pathway-specific late phase of LTP in the amygdala that is mediated by PKA and dependent on protein synthesisLearning & Memory, 2007
- Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memoriesMolecular Psychiatry, 2007
- Amygdala BDNF signaling is required for consolidation but not encoding of extinctionNature Neuroscience, 2006
- The yin and yang of neurotrophin actionNature Reviews Neuroscience, 2005