PMID- 30055019 OWN - NLM STAT- MEDLINE DCOM- 20191101 LR - 20230928 IS - 1469-7793 (Electronic) IS - 0022-3751 (Print) IS - 0022-3751 (Linking) VI - 596 IP - 18 DP - 2018 Sep TI - Uncovering a critical period of synaptic imbalance during postnatal development of the rat visual cortex: role of brain-derived neurotrophic factor. PG - 4511-4536 LID - 10.1113/JP275814 [doi] AB - KEY POINTS: With daily electrophysiological recordings and neurochemical analysis, we uncovered a transient 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 changes, if any, during the critical period. We found that (i) against a gradual increase in excitation and inhibition with age, a transient period of synaptic and neurochemical imbalance existed with suppressed excitation and enhanced inhibition at postnatal days 28 to 33/34; (ii) during this window, the expression of BDNF and tropomyosin-related kinase B (TrkB) receptors decreased, along with glutamatergic GluN1 and GluA1 receptors and the metabolic marker cytochrome oxidase, whereas that of GABA(A) Ralpha1 receptors continued to rise; (iii) monocular deprivation reduced both excitatory and inhibitory synaptic activity and neurochemicals mainly during this period; and (iv) in vivo TrkB agonist partially reversed the synaptic imbalance in normal and monocularly-deprived neurons during this time, whereas a TrkB antagonist accentuated the imbalance. Thus, our findings highlight a transitory period of synaptic imbalance with a negative relationship between BDNF and inhibitory GABA. This brief critical period may be necessary in transitioning from an immature to a more mature state of visual cortical functioning. CI - (c) 2018 The Authors. The Journal of Physiology (c) 2018 The Physiological Society. FAU - Zhang, Hanmeng AU - Zhang H AD - Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Mu, Lianwei AU - Mu L AD - Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Wang, Dandan AU - Wang D AD - Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Xia, Dongdong AU - Xia D AUID- ORCID: 0000-0001-5244-5827 AD - Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Salmon, Alexander AU - Salmon A AUID- ORCID: 0000-0002-4302-311X AD - Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Liu, Qiuli AU - Liu Q AD - Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Wong-Riley, Margaret T T AU - Wong-Riley MTT AD - Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA. LA - eng GR - P30 EY001931/EY/NEI NIH HHS/United States GR - R01 EY018441/EY/NEI NIH HHS/United States GR - T32 EY014537/EY/NEI NIH HHS/United States GR - P30EY001931/HHS | NIH | National Eye Institute (NEI)/International PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20180818 PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, GABA-A) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM CIN - J Physiol. 2019 Feb;597(3):673-675. PMID: 30506569 MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Female MH - Male MH - *Neurogenesis MH - Rats MH - Rats, Long-Evans MH - Rats, Sprague-Dawley MH - Receptor, trkB/metabolism MH - Receptors, GABA-A/metabolism MH - Receptors, N-Methyl-D-Aspartate/metabolism MH - Synapses/metabolism/*physiology MH - *Synaptic Potentials MH - Visual Cortex/growth & development/metabolism/*physiology PMC - PMC6138289 OTO - NOTNLM OT - BDNF OT - critical period OT - immunohistochemistry OT - monocular deprivation OT - patch-clamp recording OT - visual cortex EDAT- 2018/07/29 06:00 MHDA- 2019/11/02 06:00 PMCR- 2019/09/15 CRDT- 2018/07/29 06:00 PHST- 2018/07/02 00:00 [received] PHST- 2018/07/26 00:00 [accepted] PHST- 2018/07/29 06:00 [pubmed] PHST- 2019/11/02 06:00 [medline] PHST- 2018/07/29 06:00 [entrez] PHST- 2019/09/15 00:00 [pmc-release] AID - TJP13176 [pii] AID - 10.1113/JP275814 [doi] PST - ppublish SO - J Physiol. 2018 Sep;596(18):4511-4536. doi: 10.1113/JP275814. Epub 2018 Aug 18.