Mechanisms Of Synaptic Plasticity In The Adult

对于神经科学家和整个社会来说，一个关键问题涉及到遗传和环境在人脑出生后发育中的相对作用。环境刺激的范围很广，从有害的(例如化学毒物)到有益的(母亲的指示)，但所有这些都有可能影响儿童的发育计划，正如其基因组所指示的那样。突触和发育可塑性小组的研究重点是确定1)大脑中的连接(突触)如何长期变化以响应神经元活动，2)出生后早期发育期间的突触可塑性与成人的可塑性有何不同，以及3)经验如何通过在发育过程中消除突触来塑造大脑电路。虽然只运行了六个月，但我们在制定一些方法方面取得了重大进展，这些方法将用于实现上述第一个项目。我们认为，突触效能的长期变化需要表达新的RNA，为此，我们将重点放在神经元动作电位对基因表达的调节上。为了测量由动作电位调节的酶活性，我们开发了一种从体外首次受到电刺激的少量脑组织中分离细胞核的方法。我们还完善了一种使用蛋白质/DNA阵列来测量多达96个转录因子的激活的方法。这些技术将允许通过神经元活动来检查转录调控，并将导致理解可塑性所需的基因是如何调控的。与上面列出的其他目标一起，这些研究应该会让我们更好地理解环境因素如何在大脑发育中发挥作用，以便我们可以开始解决由毒物暴露引起的脑部疾病的相关问题。

A critical issue for both neuroscientists and society at large concerns the relative roles of genetics and environment in the postnatal development of the human brain. Environmental stimuli are wide ranging, from the detrimental (chemical toxicants, for example) to the beneficial (a mother's instructions), but all have the potential to influence the developmental program of a child as directed by its genome. The research done in the Synaptic and Developmental Plasticity Group focuses on determining 1) how the connections in the brain (synapses) change on a long-term basis in response to neuronal activity, 2) how synaptic plasticity during early postnatal development is different from plasticity in the adult, and 3) how experience shapes brain circuitry through synapse elimination during development. Though only in operation for six months, we have made significant progress in developing some of the methodologies that will be used in achieving the first of the aforementioned projects. We believe that long-term changes in synaptic efficacy require expression of new RNA and toward that end, we have focused on the regulation of gene expression by neuronal action potentials. To measure enzyme activity modulated by action potentials, we have developed a method for isolating nuclei from small amounts of brain tissue, which had first been electrically stimulated in vitro. We have also perfected a method of measuring the activation of up to 96 transcription factors using a protein/DNA array. These techniques will allow the examination of transcriptional regulation by neuronal activity and will lead to an understanding of how genes required for plasticity are regulated. Together with the other goals listed above, these studies should bring us a better appreciation of how environmental factors play a role in brain development so that we may begin to address the associated problems of brain disease caused by toxicant exposure.