Learning-related fine-scale specificity imaged in motor cortex circuits of behaving mice
Learning-related fine-scale specificity imaged in motor cortex circuits of behaving mice
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DOI：
10.1038/nature08897
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发表时间：
2010-04-22
期刊：
影响因子：
64.8
通讯作者：
Svoboda, Karel
中科院分区：
文献类型：
--
作者：
Komiyama, Takaki;Sato, Takashi R.;Svoboda, Karel
皮层神经元形成特定的回路（1），但这种微结构的功能结构及其与行为的关系知之甚少。双光子钙成像可以监测哺乳动物皮层中空间定义的神经元集合的活动（2-5）。在这里，我们将这种技术应用于执行选择行为的小鼠的运动皮层。训练头部固定的小鼠对两种气味中的一种做出舔的反应，而对另一种气味不舔（6，7）。小鼠通常在第一次行为会话和跨会话中表现出显著的学习。微刺激（8，9）和跨突触追踪（10，11）确定了两个不重叠的候选舌运动皮质区。使任一区域失活会损害自愿舔。2/3层的成像显示两个区域的神经元具有不同的反应类型。活动在大约一半的成像神经元区分审判类型与不同的行动。许多神经元表现出与动作一致或在动作之前的调制，与它们参与运动控制一致。不同反应类型的神经元在空间上相互混杂。附近的神经元（类似于150毫米）表现出明显的一致活动。这些时间相关性随着行为会话内和跨行为会话的学习而增加，特别是对于具有相似响应类型的神经元对。我们提出，在特定的合奏功能相关的神经元的相关活动是学习相关的电路可塑性的签名。我们的发现揭示了额叶皮层的精细和动态组织，这可能是灵活行为的基础。
Cortical neurons form specific circuits(1), but the functional structure of this microarchitecture and its relation to behaviour are poorly understood. Two-photon calcium imaging can monitor activity of spatially defined neuronal ensembles in the mammalian cortex(2-5). Here we applied this technique to the motor cortex of mice performing a choice behaviour. Head-fixed mice were trained to lick in response to one of two odours, and to withhold licking for the other odour(6,7). Mice routinely showed significant learning within the first behavioural session and across sessions. Microstimulation(8,9) and trans-synaptic tracing(10,11) identified two non-overlapping candidate tongue motor cortical areas. Inactivating either area impaired voluntary licking. Imaging in layer 2/3 showed neurons with diverse response types in both areas. Activity in approximately half of the imaged neurons distinguished trial types associated with different actions. Many neurons showed modulation coinciding with or preceding the action, consistent with their involvement in motor control. Neurons with different response types were spatially intermingled. Nearby neurons (within similar to 150 mm) showed pronounced coincident activity. These temporal correlations increased with learning within and across behavioural sessions, specifically for neuron pairs with similar response types. We propose that correlated activity in specific ensembles of functionally related neurons is a signature of learning-related circuit plasticity. Our findings reveal a fine-scale and dynamic organization of the frontal cortex that probably underlies flexible behaviour.