Prefrontal - subthalamic pathway supports action selection in a spatial working memory task
Prefrontal - subthalamic pathway supports action selection in a spatial working memory task
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DOI：
10.1038/s41598-020-67185-1
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发表时间：
2020-06-26
影响因子：
4.6
通讯作者：
Ponomarenko, Alexey
中科院分区：
文献类型：
--
作者：
Heikenfeld, Carla;Mederos, Sara;Ponomarenko, Alexey
丘脑底核（Subthalamic nucleus，简称丘脑底核）是基底神经节中前馈兴奋的主要来源，也是运动障碍治疗性脑深部电刺激的主要靶点。在电刺激过程中，运动症状的减轻可能伴随着在相互冲突的选择之间快速选择的能力的下降。丘脑底区（ST）的皮质传入包括内侧前额叶皮质（mPFC）的投射，但对前额叶-丘脑底协调及其与决策的相关性知之甚少。在这里，我们结合电生理记录与光遗传学操作的预测，从mPFC到ST在小鼠进行空间工作记忆任务（T-迷宫）或探索高架十字迷宫（焦虑测试）。我们发现，伽马振荡（30- 70 Hz）在θ（5- 10 Hz）处在mPFC和ST之间协调，并且在亚θ（2- 5 Hz）频率处效率较低。区域之间的θ/γ交叉频率耦合的光遗传学失谐进入亚θ范围损害了T-迷宫中的表现，但不影响高架十字迷宫中的焦虑相关行为。mPFC-ST通路的失谐和抑制都导致T-迷宫中重复的错误选择。这些影响与焦虑和运动活动指标的变化无关。我们的研究结果表明，在认知要求高的任务中，动作选择至关重要地涉及前额叶-底丘脑通路中伽马振荡信号的θ节律协调。
Subthalamic nucleus (STN) is the main source of feed-forward excitation in the basal ganglia and a main target of therapeutic deep brain stimulation in movement disorders. Alleviation of motor symptoms during STN stimulation can be accompanied by deterioration of abilities to quickly choose between conflicting alternatives. Cortical afferents to the subthalamic region (ST), comprising STN and zona incerta (ZI), include projections from the medial prefrontal cortex (mPFC), yet little is known about prefrontal-subthalamic coordination and its relevance for decision-making. Here we combined electrophysiological recordings with optogenetic manipulations of projections from mPFC to ST in mice as they performed a spatial working memory task (T-maze) or explored an elevated plus maze (anxiety test). We found that gamma oscillations (30-70Hz) are coordinated between mPFC and ST at theta (5-10Hz) and, less efficiently, at sub-theta (2-5Hz) frequencies. An optogenetic detuning of the theta/gamma cross-frequency coupling between the regions into sub-theta range impaired performance in the T-maze, yet did not affect anxiety-related behaviors in the elevated plus maze. Both detuning and inhibition of the mPFC-ST pathway led to repeated incorrect choices in the T-maze. These effects were not associated with changes of anxiety and motor activity measures. Our findings suggest that action selection in a cognitively demanding task crucially involves theta rhythmic coordination of gamma oscillatory signaling in the prefrontal-subthalamic pathway.