A Local Reduction in Cortical GABAergic Synapses after a Loss of Endogenous Brain-Derived Neurotrophic Factor, as Revealed by Single-Cell Gene Knock-Out Method
| Autor: | Keigo Kohara, Yan Huang, Hiroki Yasuda, Tadaharu Tsumoto, Naoki Adachi, Kazuhiro Sohya |
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| Rok vydání: | 2007 |
| Předmět: |
Mice
Transgenic Inhibitory postsynaptic potential Mice Neurotrophic factors Postsynaptic potential medicine Animals gamma-Aminobutyric Acid Visual Cortex Neurons Brain-derived neurotrophic factor Mice Inbred BALB C biology Brain-Derived Neurotrophic Factor General Neuroscience Neural Inhibition Articles medicine.anatomical_structure nervous system Synapses biology.protein GABAergic Soma Neuron Neuroscience Gene Deletion Neurotrophin |
| Zdroj: | The Journal of Neuroscience. 27:7234-7244 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1943-07.2007 |
| Popis: | To address questions of whether brain-derived neurotrophic factor (BDNF) released from active excitatory neurons acts locally only on GABAergic presynaptic terminals contacting these neurons or generally also on GABAergic terminals contacting other inactive neurons, we developed a single-cell gene knock-out method in organotypic slice culture of visual cortex of floxedBDNFtransgenic mice. A biolistic transfection of Cre recombinase with green fluorescence protein (GFP) plasmids to layer II/III of the cortex resulted in loss of BDNF in a single neuron or a small number of neurons, which expressed GFP at 13–14 din vitro. Analysis within situhybridization and immunohistochemistry confirmed that neurons expressing GFP lacked BDNF mRNA and protein, respectively. Analysis with immunohistochemistry using antibody against GABA synthesizing enzyme showed that the number of GABAergic terminals on the soma of BDNF knock-out neurons was smaller than that of neighboring control neurons. Morphological analysis indicated that there was no significant difference in the soma size and branch points and length of dendrites between the BDNF knock-out and control neurons. Recordings of miniature IPSCs (mIPSCs) showed that the frequency of mIPSCs of BDNF knock-out neurons was lower than that of control neurons, although the amplitude was not significantly different, suggesting the smaller number of functional GABAergic synapses on whole the BDNF knock-out neuron. The present results suggest that BDNF released from postsynaptic target neurons promotes the formation or proliferation of GABAergic synapses through its local actions in layer II/III of visual cortex. |
| Databáze: | OpenAIRE |
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