Regulation of visual cortical synaptic plasticity and experience-dependent functional development by cytokine

2012 Fiscal Year Final Research Report

• Project/Area Number: 23650165
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neuroscience in general
• Research Institution: Nagoya University
• Principal Investigator: KOMATSU Yukio 名古屋大学, 環境医学研究所, 教授 (90135343)
• Project Period (FY): 2011 – 2012
• Keywords: 経験依存的発達 / 可塑性 / 視覚野 / サイトカイン / スケーリング / 長期増強 / T型Ca2+チャネル

Research Abstract

In rodents, monocular deprivation produces depression of visual cortical responses evoked by the stimulation of deprived eye at 3 days after the start of the deprivation during the critical period of visual cortical development, and produces potentiation of visual cortical responses evoked by the stimulation of non-deprived eye when the deprivation is continued for 4 or more days. The potentiation is prevented by the blockade of T-type Ca2+ channel-dependent long-term potentiation (T-LTP). The potentiation is also prevented by a deficiency of TNF-α, which is known to mediate the increase of quantal amplitude of excitatory synaptic currents via the synaptic scaling mechanism. These observations suggest that the potentiation of non-deprived eye responses is mediated by either T-LTP or synaptic scaling. I investigated these two possibilities in this study. Visual cortical slices were prepared from rats after 3 or 6 days of monocular deprivation and from control rats, and miniature excitatory synaptic currents (mEPSCs) were recorded from layer 2/3 pyramidal cells in the binocular region using the whole-cell recording method. No significant differences were found in the mEPSC amplitude between the 3 groups of rats, indicating that monocular deprivation did not initiate synaptic scaling. In rat visual cortical slices, the pharmacological blockade of the action of TNF-α prevented T-LTP production. In slices prepared from TNF-αknockout mice, T-LTP did not occur and it was rescued by the addition of TNF-α. These results demonstrate that TNF-α is required for the production of T-LTP and suggest that the failure of potentiation of non-deprived eye responses in TNF-α knockout mice is ascribed to the deficiency of T-LTP, but not synaptic scaling.