Neural plasticity maintained high by activation of cyclic AMP-dependent protein kinase: an age-independent, general mechanism in cat striate cortex.
Neural plasticity maintained high by activation of cyclic AMP-dependent protein kinase: an age-independent, general mechanism in cat striate cortex.
复制标题
通过激活环 AMP 依赖性蛋白激酶来维持较高的神经可塑性：猫纹状皮层中的一种与年龄无关的一般机制。
DOI：
10.1016/j.neuroscience.2007.04.041
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发表时间：
2007
期刊：
影响因子：
3.3
通讯作者：
Tanaka,S
中科院分区：
文献类型：
--
作者：
Imamura,K;Kasamatsu,T;Tanaka,S
成年猫缺乏眼优势可塑性，单眼剥夺后眼优势分布变化不大。在连续输注了儿茶酚胺能神经毒素、β-肾上腺素受体阻滞剂或环腺苷酸依赖性蛋白激酶（蛋白激酶A）抑制剂的小猫视皮层中，眼优势可塑性也丧失。作为补充，在成年猫中，我们早些时候表明，蛋白激酶A的药理学激活，虽然部分，恢复眼优势可塑性。在本研究中，我们首先询问是否通过蛋白激酶A激活介导，相同的分子机制可以恢复小猫皮层的眼优势可塑性，因为先前的药物治疗导致小猫皮层失去了可塑性的表达。同时单眼剥夺，两种环AMP相关药物（霍乱毒素A亚基或双丁酰环AMP）直接注入两种类型的再生障碍性小猫皮质预处理与6-羟基多巴胺或普萘洛尔。联合治疗导致明显的眼优势转移到非剥夺眼，表明皮质可塑性完全恢复到再生障碍性小猫皮质。接下来，为了直接证明未成熟和成熟皮层之间蛋白激酶A激活的敏感性差异，我们将在小猫中获得的数据与在可比实验范式下来自成年猫的已发表数据进行了比较。单眼剥夺后的眼优势变化的程度进行了比较，在不同的药物浓度在两个制剂：转移眼优势分布在再生障碍性小猫皮质灌注双丁酰环AMP在最低浓度的测试和W形分布在类似的治疗成人皮质在一千倍更高的药物浓度，诱导几乎最大的变化。我们的结论是，无论动物的年龄，蛋白激酶A级联的激活是一个普遍的机制，以保持眼优势可塑性高，其敏感性显着高于在未成熟的成熟皮层。
Adult cats lack ocular dominance plasticity, showing little change in the ocular dominance distribution following monocular deprivation. Ocular dominance plasticity is also lost in kitten visual cortex that has been continuously infused with either catecholaminergic neurotoxin, β-adrenoreceptor blocker, or inhibitor of cyclic AMP-dependent protein kinase (protein kinase A). Complementarily, in adult cats we showed earlier that pharmacological activation of protein kinase A, albeit partially, restored ocular dominance plasticity. In the present study, we first asked whether, mediated by protein kinase A activation, the same molecular mechanisms could restore ocular dominance plasticity to kitten cortex that once lost the expression of plasticity due to prior pharmacological treatments. Concurrently with monocular deprivation, two kinds of cyclic AMP-related drugs (cholera toxin A-subunit or dibutyryl cyclic AMP) were directly infused in two types of aplastic kitten cortex pretreated with either 6-hydroxydopamine or propranolol. The combined treatment resulted in clear ocular dominance shift to the non-deprived eye, indicating that cortical plasticity was fully restored to aplastic kitten cortex. Next, to directly prove the sensitivity difference in protein kinase A activation between the immature and mature cortex, we compared the thus-obtained data in kittens with the published data derived from adult cats under the comparable experimental paradigm. The extent of ocular dominance changes following monocular deprivation was compared at different drug concentrations in the two preparations: the shifted ocular dominance distribution in aplastic kitten cortex infused with dibutyryl cyclic AMP at the lowest concentration tested and the W-shaped distribution in similarly treated adult cortex at a thousandfold-higher drug concentration that induced nearly maximal changes. We conclude that, irrespective of the animal’s age, activation of protein kinase A cascades is a general mechanism to maintain ocular dominance plasticity high, their sensitivity being substantially higher in the immature than mature cortex.