Open AccessAge‐related changes in hippocampal‐dependent synaptic plasticity and memory mediated by p75 neurotrophin receptor
Author(s) -
Wong LikWei,
Chong Yee Song,
Lin Wei,
Kisiswa Lilian,
Sim Eunice,
Ibáñez Carlos F.,
Sajikumar Sreedharan
Publication year - 2021
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13305
Subject(s) - metaplasticity , neuroscience , synaptic plasticity , biology , nonsynaptic plasticity , neuroplasticity , homeostatic plasticity , memory consolidation , hippocampal formation , developmental plasticity , neurotrophin , homosynaptic plasticity , hippocampus , plasticity , receptor , genetics , physics , thermodynamics
The plasticity mechanisms in the nervous system that are important for learning and memory are greatly impacted during aging. Notably, hippocampal‐dependent long‐term plasticity and its associative plasticity, such as synaptic tagging and capture (STC), show considerable age‐related decline. The p75 neurotrophin receptor (p75 NTR ) is a negative regulator of structural and functional plasticity in the brain and thus represents a potential candidate to mediate age‐related alterations. However, the mechanisms by which p75 NTR affects synaptic plasticity of aged neuronal networks and ultimately contribute to deficits in cognitive function have not been well characterized. Here, we report that mutant mice lacking the p75 NTR were resistant to age‐associated changes in long‐term plasticity, associative plasticity, and associative memory. Our study shows that p75 NTR is responsible for age‐dependent disruption of hippocampal homeostatic plasticity by modulating several signaling pathways, including BDNF, MAPK, Arc, and RhoA‐ROCK2‐LIMK1‐cofilin. p75 NTR may thus represent an important therapeutic target for limiting the age‐related memory and cognitive function deficits.