Genetic recovery of ErbB4 in adulthood partially restores brain functions in null mice

Abstract

Neurotrophic factor NRG1 and its receptor ErbB4 play a role in GABAergic circuit assembly during development. ErbB4 null mice possess fewer interneurons, have decreased GABA release, and show impaired behavior in various paradigms. In addition, NRG1 and ErbB4 have also been implicated in regulating GABAergic transmission and plasticity in matured brains. However, current ErbB4 mutant strains are unable to determine whether phenotypes in adult mutant mice result from abnormal neural development. This important question, a glaring gap in understanding NRG1–ErbB4 function, was addressed by using two strains of mice with temporal control of ErbB4 deletion and expression, respectively. We found that ErbB4 deletion in adult mice impaired behavior and GABA release but had no effect on neuron numbers and morphology. On the other hand, some deficits due to the ErbB4 null mutation during development were alleviated by restoring ErbB4 expression at the adult stage. Together, our results indicate a critical role of NRG1–ErbB4 signaling in GABAergic transmission and behavior in adulthood and suggest that restoring NRG1–ErbB4 signaling at the postdevelopmental stage might benefit relevant brain disorders.

Metformin Enhances Excitatory Synaptic Transmission onto Hippocampal CA1 Pyramidal Neurons

“…For miniature excitatory postsynaptic current (mEPSC) recording, pyramidal neurons were held at −70 mV in the presence of 20 µM bicuculline and 1 µM TTX, with the pipette solution containing: 125 mM K-gluconate, 5 mM KCl, 10 mM HEPES, 0.2 mM EGTA, 1 mM MgCl 2 , 4 mM Mg-ATP, 0.3 mM Na-GTP and 10 mM phosphocreatine (pH 7.35, 290 mOsm). For miniature inhibitory postsynaptic current (mIPSC) recording, pyramidal neurons were held at −70 mV in the presence of 20 µM CNQX, 50 µM DL-AP5 and 1 µM TTX, with the pipette solution containing: 130 mM CsCl, 10 mM HEPES, 0.2 mM EGTA, 1 mM MgCl 2 , 4 mM Mg-ATP, 0.3 mM Na-GTP, mM 10 phosphocreatine and 5 mM QX314 (pH 7.35, 290 mOsm) [ 27 ].…”

Agrin-Lrp4-Ror2 signaling regulates adult hippocampal neurogenesis in mice

“…Flag-tagged Lrp4 and Ror2 were immunoprecipitated with Flag M2 beads (SigmaA2220) and anti-Ror2 antibodies. Western blotting was performed as described previously (Wang et al, 2018). Three independent experiments were performed.…”

Neuregulin1-ErbB4 Signaling in Spinal Cord Participates in Electroacupuncture Analgesia in Inflammatory Pain

“…NRG1 ( Lacroix-Fralish et al, 2008 ; Calvo et al, 2010 ), ecto-ErbB4 ( Woo et al, 2007 ) and AG-1478 ( Araldi et al, 2018 ) were delivered intrathecally at concentration of 10 nM, 1 μg/mL, and 5 μM in a volume of 2 μL, respectively, for 3 consecutive days after intraplantar injection of CFA. Tamoxifen was administrated following our previous protocols with modification ( Wang et al, 2018a ). Simply, Tamoxifen (Sigma-Aldrich) was dissolved in corn oil at 20 mg/ml.…”