J Physiol 0.0 (2018) pp 1–26 1 The Journal of Physiology Uncovering a critical period of synaptic imbalance during postnatal development of the rat visual cortex: role of brain-derived neurotrophic factor Hanmeng Zhang ‡ , Lianwei Mu †, ‡ , Dandan Wang ‡ , Dongdong Xia ‡ , Alexander Salmon , Qiuli Liu ∗ and Margaret T. T. Wong-Riley Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA Edited by: Ole Paulsen & Jesper Sj¨ ostr¨ om Key points  With daily electrophysiological recordings and neurochemical analysis, we uncovered a trans- ient period of synaptic imbalance between enhanced inhibition and suppressed excitation in rat visual cortical neurons from the end of the fourth toward the end of the fifth postnatal weeks.  The expression of brain-derived neurotrophic factor (BDNF), which normally enhances excitation and suppresses inhibition, was down-regulated during that time, suggesting that this may contribute to the inhibition/excitation imbalance.  An agonist of the BDNF receptor tropomyosin-related kinase B (TrkB) partially reversed the imbalance, whereas a TrkB antagonist accentuated the imbalance during the transient period.  Monocular lid suture during the transient period is more detrimental to the function and neurochemical properties of visual cortical neurons than before or after this period.  We regard the period of synaptic imbalance as the peak critical period of vulnerability, and its existence is necessary for neurons to transition from immaturity to a more mature state of functioning. Abstract The mammalian visual cortex is immature at birth and undergoes postnatal structural and functional adjustments. The exact timing of the vulnerable period in rodents remains unclear. The critical period is characterized by inhibitory GABAergic maturation reportedly dependent on brain-derived neurotrophic factor (BDNF). However, most of the studies were performed on experimental/transgenic animals, questioning the relationship in normal animals. The present study aimed to conduct in-depth analyses of the synaptic and neurochemical development of visual cortical neurons in normal and monocularly-deprived rats and to determine specific Hanmeng Zhang received her BS degree (MD equivalent) from the Sport Science College of Beijing Sport University, Beijing, China, and is currently a graduate student at the Medical College of Wisconsin, Milwaukee, WI, USA. Lianwei Mu received his BS degree from Weifang Medical University, Weifang, China, and is currently a PhD student at the Sport Science College of Beijing Sport University, Beijing, China. Dandan Wang received her BS and Master of Medicine degrees from the Shanxi Medical University, Shanxi, China, and is currently enrolled as a graduate student at the Medical College of Wisconsin, Milwaukee, WI, USA. Dongdong Xia received her BS degree from Beijing Sport University, Beijing, China, where she is pursuing a master’s degree working in the Wong-Riley laboratory. ∗ Present address: Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA † Present address: Department of Exercise Physiology, Beijing Sport University, Beijing, China ‡ These authors contributed equally to this work. C  2018 The Authors. The Journal of Physiology C  2018 The Physiological Society DOI: 10.1113/JP275814