Open AccessBDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury
Author(s) -
Lichao Huang,
Jianhua Jin,
Kai Chen,
Shijun You,
Hongyang Zhang,
Alexandra Sideris,
Monica Norcini,
Esperanza Recio-Pinto,
Jing Wang,
WenBiao Gan,
Guang Yang
Publication year - 2021
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3001337
Subject(s) - microglia , peripheral nerve injury , neuroscience , nerve injury , brain derived neurotrophic factor , neurotrophic factors , allodynia , neuroplasticity , somatosensory system , neurotrophin , biology , cerebral cortex , medicine , hyperalgesia , inflammation , sciatic nerve , anatomy , receptor , nociception , immunology
Peripheral nerve injury–induced mechanical allodynia is often accompanied by abnormalities in the higher cortical regions, yet the mechanisms underlying such maladaptive cortical plasticity remain unclear. Here, we show that in male mice, structural and functional changes in the primary somatosensory cortex (S1) caused by peripheral nerve injury require neuron-microglial signaling within the local circuit. Following peripheral nerve injury, microglia in the S1 maintain ramified morphology and normal density but up-regulate the mRNA expression of brain-derived neurotrophic factor (BDNF). Using in vivo two-photon imaging and Cx3cr1 CreER ; Bdnf flox mice, we show that conditional knockout of BDNF from microglia prevents nerve injury–induced synaptic remodeling and pyramidal neuron hyperactivity in the S1, as well as pain hypersensitivity in mice. Importantly, S1-targeted removal of microglial BDNF largely recapitulates the beneficial effects of systemic BDNF depletion on cortical plasticity and allodynia. Together, these findings reveal a pivotal role of cerebral microglial BDNF in somatosensory cortical plasticity and pain hypersensitivity.