Center for Neural Science, New York University, New York, NY 10003.
Liberal Studies, New York University, New York, NY 10003.
Proc Natl Acad Sci U S A. 2023 Oct 3;120(40):e2300595120. doi: 10.1073/pnas.2300595120. Epub 2023 Sep 25.
Transforming growth factor β (TGFβ) is required for long-term memory (LTM) for sensitization in . When LTM is induced using a two-trial training protocol, TGFβ inhibition only blocks LTM when administrated at the second, not the first trial. Here, we show that TGFβ acts as a "repetition detector" during the induction of two-trial LTM. Secretion of the biologically inert TGFβ proligand must coincide with its proteolytic activation by the Bone morphogenetic protein-1 (BMP-1/Tolloid) metalloprotease, which occurs specifically during trial two of our two-trial training paradigm. This paradigm establishes long-term synaptic facilitation (LTF), the cellular correlate of LTM. BMP-1 application paired with a single serotonin (5HT) pulse induced LTF, whereas neither a single 5HT pulse nor BMP-1 alone effectively did so. On the other hand, inhibition of endogenous BMP-1 activity blocked the induction of two-trial LTF. These results suggest a unique role for TGFβ in the interaction of repeated trials: during learning, repeated stimuli engage separate steps of the TGFβ cascade that together are necessary for the induction of long-lasting memories.
转化生长因子β（TGFβ）是. 诱导敏感化长时程记忆（LTM）所必需的。当使用两试训练方案诱导 LTM 时，TGFβ 抑制仅在第二次而不是第一次试验时给药时才会阻断 LTM。在这里，我们表明 TGFβ 在两试 LTM 的诱导中充当“重复检测器”。生物惰性 TGFβ 前配体的分泌必须与其由骨形态发生蛋白-1（BMP-1/Tolloid）金属蛋白酶的蛋白水解激活同时发生，这在我们的两试训练范例的第二次试验中特异性地发生。该范例建立了长时程突触易化（LTF），这是 LTM 的细胞相关性。BMP-1 与单个 5-羟色胺（5HT）脉冲联合应用诱导了 LTF，而单独的 5HT 脉冲或 BMP-1 均不能有效地诱导。另一方面，内源性 BMP-1 活性的抑制阻断了两试 LTF 的诱导。这些结果表明 TGFβ 在重复试验的相互作用中具有独特的作用：在学习过程中，重复的刺激会引发 TGFβ 级联的单独步骤，这些步骤共同是诱导持久记忆所必需的。
