Otx 2 Protein & Critical Period
Trigger for Brain Plasticity Identified
http://www.newswise.com/articles/view/543111/
Researchers have long sought a factor that can trigger the brain’s ability to learn – and perhaps recapture the “sponge-like” quality of childhood. In the August 8 issue of the journal Cell, neuroscientists at Children's Hospital Boston report that they’ve identified such a factor, a protein called Otx 2.
Otx2 helps a key type of cell in the cortex to mature, initiating a critical period -- a window of heightened brain plasticity, when the brain can readily make new connections.
貴夫Takao K. Hensch, PhD, of the Neurobiology Program and Department of Neurology at Children’s, the study’s senior investigator, speculates that there may be similar factors from the auditory, olfactory and other sensory systems that help time critical periods.
2008 美科學家發現恢復神經可塑性方法
http://big5.lrn.cn/
共焦点レーザ顕微鏡画像からの脳神経の三次元形態解析 ○佐藤康平，青木義満(芝浦工大)，俣賀宣子，Takao K Hensch(理研)
據美國《技術評論》雜誌
大腦在發育過程中有一個可塑性的“臨界時期”，在此階段，景象和聲音等外界刺激對不同大腦系統的正常發育非常重要。1歲到3歲的嬰兒需要經常性的視覺刺激以使他們的視覺系統形成適當的神經回路，如果在此期間，一隻眼睛被損壞或者出現弱視，視覺可能永遠無法恢復。
波士頓兒童醫院的有森貴夫·亨施團隊研究了弱視的老鼠，他們發現存在兩個機制控制著這個臨界時期。
亨施團隊以前的研究證明，一個特定的名為籃狀細胞的細胞能引起神經可塑性的出現，這些細胞被分子網路包圍。亨施說：“當分子網路非常緊密地包裹這些細胞時，臨界時期結束。”於是，收緊這個網路的軟骨素酶能重新恢復成年人神經的可塑性。
亨施和他的同事發現，籃狀細胞的生長受到名為Otx2的蛋白質的控制，這個蛋白質的過度表達可能引發可塑性的臨界時期。亨施提到，儘管這個發現主要是針對視覺系統的，但是其他的感應系統也擁有籃狀細胞，其工作機制可能一樣。
控製成年人神經可塑性的第二個機制是阻止神經系統產生的用來阻止神經生長的抑制分子。亨施說：“神經系統排斥正在成長的新軸突（連接細胞的神經部分），這是為什麼脊髓損傷後很難恢復的原因。”
髓磷脂細胞在軸突周圍形成了一個絕緣層，可以隱藏許多抑制分子。通過使用某些鬆開髓磷脂的藥物來做試驗，亨施團隊發現，他們能夠使成年老鼠趨於穩定的視覺系統重新恢復活力，使弱視的老鼠恢復視力。然而，研究中使用的這個藥物是有毒的，它不可能成為一個有用的治療。
為了成功地獲得年輕人大腦的可塑性，科學家將很可能需要非常精準地找到治療方法。哈佛醫學院的神經科學家約書亞·桑尼斯說：“一旦我們理解了可塑性背後的機制，我們能夠設計治療方案來更好地利用它。”
1998 Local GABA Circuit Control of Experience-Dependent Plasticity in Developing Visual Cortex
Science 20 November 1998: 1504
http://www.sciencemag.org/cgi/content/abstract/282/5393/1504
Sensory experience in early life shapes the mammalian brain. An impairment in the activity-dependent refinement of functional connections within developing visual cortex was identified here in a mouse model. Gene-targeted disruption of one isoform of glutamic acid decarboxylase prevented the competitive loss of responsiveness to an eye briefly deprived of vision, without affecting cooperative mechanisms of synapse modification in vitro. Selective, use-dependent enhancement of fast intracortical inhibitory transmission with benzodiazepines restored plasticity in vivo, rescuing the genetic defect. Specific networks of inhibitory interneurons intrinsic to visual cortex may detect perturbations in sensory input to drive experience-dependent plasticity during development.
2005 Critical period plasticity in local cortical circuits TK Hensch - Nat Rev Neurosci, 2005 - healthsystem.virginia.edu
1998 Comparison of Plasticity In Vivo and In Vitro in the Developing Visual Cortex of Normal and Protein Kinase A RI
-Deficient Mice
http://www.jneurosci.org/cgi/content/abstract/18/6/2108
TK Hensch, JA Gordon, EP Brandon, GS McKnight, RL … - Journal of Neuroscience, 1998 - Soc Neuroscience
The Journal of Neuroscience, March 15, 1998, 18(6):2108-2117
Developing sensory systems are sculpted by an activity-dependent strengthening and weakening of connections. Long-term potentiation (LTP) and depression (LTD) in vitro have been proposed to model this experience-dependent circuit refinement. We directly compared LTP and LTD induction in vitro with plasticity in vivo in the developing visual cortex of a mouse mutant of protein kinase A (PKA), a key enzyme implicated in the plasticity of a diverse array of systems.
In mice lacking the RI
regulatory subunit of PKA, we observed three abnormalities of synaptic plasticity in layer II/III of visual cortex in vitro. These included an absence of (1) extracellularly recorded LTP, (2) depotentiation or LTD, and (3) paired-pulse facilitation. Potentiation was induced, however, by pairing low-frequency stimulation with direct depolarization of individual mutant pyramidal cells. Together these findings suggest that the LTP defect in slices lacking lies in the transmission of sufficient net excitation through the cortical circuit.
Nonetheless, functional development and plasticity of visual cortical responses in vivo after monocular deprivation did not differ from normal. Moreover, the loss of all responsiveness to stimulation of the originally deprived eye in most cortical cells could be restored by reverse suture of eyelids during the critical period in both wild-type and mutant mice. Such an activity-dependent increase in response would seem to require a mechanism like potentiation in vivo. Thus, the RI isoform of PKA is not essential for ocular dominance plasticity, which can proceed despite defects in several common in vitro models of neural plasticity.
Key words: visual cortex; plasticity; development; PKA; LTP; LTD; PPF
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