Coordination Funds

哺乳动物大脑的一个基本特征是它能够获取、存储和回忆新的信息，这使得个体生物体能够灵活地适应不断变化的环境。记忆的形成依赖于神经细胞改变它们的通讯点--突触--效能的能力。这些可塑性变化取决于相关的神经元活动的沟通神经元，并表示为长时程增强（LTP）或相反的长时程抑制（LTD）的突触传递。大约50年前，在兴奋性主细胞网络中的突触能末梢首次发现了突触可塑性（Hebb，1949;布利斯& Lomo，1973）。从那时起，突触可塑性已被广泛接受为哺乳动物大脑中学习和记忆的主要细胞机制（Malenka，2003; Feldman &布雷希特，2005）。最近的研究，包括我们自己的研究，表明可塑性也存在于靶向GABA能抑制性中间神经元的突触中（INs; Isaac et al.，2007; Kullmann & Lamsa，2007; Lange等人，2012; Topolnik，2012）。此外，已经确定了IN可塑性的条件和形式的意外变化（Kullmann & Lamsa，2011），提高了IN可塑性可以以非常通用的细胞类型和突触特异性方式促进信息处理的可能性。因此，在所提出的RU中，我们的目标是以双重方法破译IN可塑性对学习和记忆的贡献。首先，在一个“自下而上”的方法，我们的目标是确定的主要细胞和分子机制的突触可塑性在INs. Second，在一个“自下而上”的方法，我们将开发和使用新的分子工具来调节一些主要的分子通路的基础上IN可塑性。在研究单位（RU）的第一个资助期，我们成功地将这种方法集中在表达小清蛋白的persoma抑制（PVI）和表达生长抑素的树突靶向中间神经元（SOMIs）的突触可塑性上。在第二个拟议的资助期内，我们的目标是遵循我们最初设定的研究路线，特别是在IN可塑性，神经元网络活动和记忆相关行为之间建立因果关系。为了实现这一目标，我们将结合联合收割机在体内和体外电生理学，神经解剖学，在体内成像，分子生物学，光遗传学，行为和计算分析在一个协调一致的，综合的和因果关系的方式。

A fundamental feature of the mammalian brain is its ability to acquire, store and recall novel information, which enables the individual organism to flexibly adapt to its changing environment. Memory formation dependents on the capacity of nerve cells to change the efficacy of their communication points, the synapses. These plastic changes depend on correlated neuronal activity of communicating neurons and are expressed as long-term potentiation (LTP) or the opposite long-term depression (LTD) of synaptic transmission. Almost 50 years ago synaptic plasticity was first identified at glutamatergic terminals in networks of excitatory principal cells (Hebb, 1949; Bliss & Lomo, 1973). Since then synaptic plasticity has been broadly accepted as the main cellular mechanism underlying learning and memory in the mammalian brain (Malenka, 2003; Feldman & Brecht, 2005). Recent investigations, including our own, demonstrated that plasticity also exists at glutamatergic synapses targeting GABAergic inhibitory interneurons (INs; Isaac et al., 2007; Kullmann & Lamsa, 2007; Lange et al., 2012; Topolnik, 2012). Moreover, an unexpected variety in the conditions and forms of IN plasticity has been identified (Kullmann & Lamsa, 2011), raising the possibility that IN plasticity could contribute to information processing in a very versatile, cell type- and synapse-specific manner. Therefore, in the proposed RU, we aim to decipher the contribution of IN plasticity to learning and memory in a dual approach. First, in a ‘bottom up’ approach, we aim to identify the main cellular and molecular mechanisms underlying synaptic plasticity in INs. Second, in a ‘bottom up’ approach we will develop and use new molecular tools to modulate some of the main molecular pathways underlying IN plasticity. In the 1st funding period of the research unit (RU) we successfully focused this approach on synaptic plasticity in parvalbumin-expressing persioma-inhibitory (PVI) and somatostatin-expressing dendrite-targeting interneurons (SOMIs). In the 2nd proposed funding period we aim to follow our initially set research lines and to particularly draw a causal link between IN plasticity, neuronal network activity and memory-relevant behaviour. To achieve this goal, we will combine in vivo and in vitro electrophysiology, neuroanatomy, in vivo imaging, molecular biology, optogenetics, behavioural and computational analyses in a concerted, integrative and causal manner.