Department of Biology and Volen National Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454-9110.
Department of Biology and Volen National Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454-9110
J Neurosci. 2022 May 25;42(21):4297-4310. doi: 10.1523/JNEUROSCI.0144-22.2022. Epub 2022 Apr 26.
In , functional imaging studies revealed that associative memory formation is coupled to a cascade of neural plasticity events in distinct compartments of the mushroom body (MB). In-depth investigation of the circuit dynamics, however, will require an model that faithfully mirrors these events to allow direct manipulations of circuit elements that are inaccessible in the intact fly. The current models have been able to reproduce the fundamental plasticity of aversive short-term memory, a potentiation of the MB intrinsic neuron (Kenyon cells [KCs]) responses after artificial learning However, this potentiation showed different localization and encoding properties from those reported and failed to generate the previously reported suppression plasticity in the MB output neurons (MBONs). Here, we develop an model using the female brain that recapitulates behaviorally evoked plasticity in the KCs and MBONs. We demonstrate that this plasticity accurately localizes to the MB α'3 compartment and is encoded by a coincidence between KC activation and dopaminergic input. The formed plasticity is input-specific, requiring pairing of the conditioned stimulus and unconditioned stimulus pathways; hence, we name it pairing-dependent plasticity. Pairing-dependent plasticity formation requires an intact gene and is blocked by previous-night sleep deprivation but is rescued by rebound sleep. In conclusion, we show that our preparation recapitulates behavioral and imaging results from intact animals and can provide new insights into mechanisms of memory formation at the level of molecules, circuits, and brain state. The mammalian LTP model enabled in-depth investigation of the hippocampal memory circuit. We develop a parallel model to study the mushroom body (MB) memory circuit. Pairing activation of the conditioned stimulus and unconditioned stimulus pathways in dissected brains induces a potentiation pairing-dependent plasticity (PDP) in the axons of α'β' Kenyon cells and a suppression PDP in the dendrites of their postsynaptic MB output neurons, localized in the MB α'3 compartment. This PDP is input-specific and requires the 3' untranslated region of Interestingly, PDP carries information about the animal's experience before dissection; brains from sleep-deprived animals fail to form PDP, whereas those from animals who recovered 2 h of their lost sleep form PDP.
在 中，功能成像研究表明，联想记忆的形成与蘑菇体（MB）不同隔室中的一系列神经可塑性事件偶联。然而，对电路动力学的深入研究将需要一个 模型，该模型忠实地反映这些事件，以便直接操纵在完整的苍蝇中无法触及的电路元件。当前的 模型已经能够再现厌恶短期记忆的基本可塑性，即在人工学习后，MB 内源性神经元（Kenyon 细胞 [KCs]）的反应增强 然而，这种增强显示出与报告的不同的本地化和编码特性 ，并且未能在 MB 输出神经元（MBONs）中产生先前报道的抑制性可塑性。在这里，我们使用雌性 脑开发了一个 模型，该模型再现了 KCs 和 MBONs 中行为引发的可塑性。我们证明，这种可塑性准确地定位于 MB α'3 隔室，并由 KC 激活和多巴胺能输入之间的巧合编码。形成的可塑性是输入特异性的，需要条件刺激和非条件刺激途径的配对；因此，我们将其命名为配对依赖性可塑性。配对依赖性可塑性的形成需要一个完整的 基因，并且会被前夜的睡眠剥夺阻断，但可以通过反弹睡眠来挽救。总之，我们表明，我们的 制备重现了完整动物的行为和成像结果，并可以在分子、电路和大脑状态水平上提供对记忆形成机制的新见解。哺乳动物的 LTP 模型使深入研究海马记忆电路成为可能。我们开发了一个平行模型来研究 蘑菇体（MB）记忆电路。在分离的大脑中，条件刺激和非条件刺激途径的激活配对会在 α'β'Kenyon 细胞的轴突中诱导出一种增强型配对依赖性可塑性（PDP），并在其突触后 MB 输出神经元的树突中诱导出一种抑制型 PDP，定位于 MB α'3 隔室。这种 PDP 是输入特异性的，需要 有趣的是， PDP 携带动物在解剖前的经验信息；来自睡眠剥夺动物的大脑无法形成 PDP，而来自恢复了 2 小时丢失睡眠的动物的大脑则形成 PDP。
