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Adult Neurogenesis

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

The impact of transgenic blockade of neurotransmitter release in newborn neurons on hippocampal dependent memory

  • P3-093
  • 浅井 裕貴 / Hirotaka Asai:1 McHugh Thomas J. / Thomas J. McHugh:2 久恒 辰博 / Tatsuhiro Hisatsune:1 
  • 1:東京大院・新領域・先端生命 / Dept.of Integrated Bioscis.,Grad.Sch.of Frontier Sciences, The Univ.of Tokyo 2:理研BSI神経回路・行動生理 / Laboratory for Circuit and Behavioral Physiology, Riken BSI, Saitama, Japan 

Adult neurogenesis, the generation of new neurons in adult mammals, occurs actively in the subgranular zone of the hippocampal dentate gyrus and the subventricular zone of the lateral ventricle. Newborn neurons in the hippocampus play an important roles in memory function. Here we examine the function of newborn neurons on hippocampal dependent memory tasks using a novel transgenic mouse (named Newborn neuron-TeTX mice) which carrys three transgenes: Nestin-CreERT2 (Imayoshi et al., 2008), αCamKII-floxed-tTA, and Tet operator- TeTX (Nakashiba et al., 2008). TeTX (tetanus toxin) cleaves VAMP2, which is required for membrane fusion of synaptic vesicles. The expression of TeTX is controlled by both the Nestin and CamKII promoters and as a result, presynaptic transmitter release is specifically blocked in adult born neurons. The expression of TeTX in adult-born neurons was confirmed by retrovirus encoded synaptophysinGFP-IRES-mCherryVAMP2 (Nakashiba et al., 2012). To investigate how the block of the presynaptic function of newborn neurons influences hippocampal dependent memory tasks, we treated 8 weeks old triple transgenic mice and control littermate mice with tamoxifen, and left them for 8 weeks in order to express TeTX in newborn neurons, then performed delayed non-matching to place (DNMP) task using the 8-arm radial maze and contextual fear discrimination task. We found in 8-arm radial maze task that triple transgenic mice show a significantly lower percentage of correct choices in first two days compared to control mice. On the other hand, in contextual fear discrimination task we observed no significant difference between genotypes. These results may suggest the function of newborn neurons in this DNMP task.

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