Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil; Núcleo de Neurociências, Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
Exp Neurol. 2018 Jun;304:90-101. doi: 10.1016/j.expneurol.2018.02.011. Epub 2018 Feb 16.
Mood disorders are associated to functional unbalance in mesolimbic and frontal cortical circuits. As a commonly used mood stabilizer, lithium acts through multiple biochemical pathways, including those activated by muscarinic cholinergic receptors crucial for hippocampal-prefrontal communication. Therefore, here we investigated the effects of lithium on prefrontal cortex responses under cholinergic drive. Lithium-treated rats were anesthetized with urethane and implanted with a ventricular cannula for muscarinic activation, a recording electrode in the medial prefrontal cortex (mPFC), and a stimulating electrode in the intermediate hippocampal CA1. Either of two forms of synaptic plasticity, long-term potentiation (LTP) or depression (LTD), were induced during pilocarpine effects, which were monitored in real time through local field potentials. We found that lithium attenuates the muscarinic potentiation of cortical LTP (<20 min) but enhances the muscarinic potentiation of LTD maintenance (>80 min). Moreover, lithium treatment promoted significant cross-frequency coupling between CA1 theta (3-5 Hz) and mPFC low-gamma (30-55 Hz) oscillations. Interestingly, lithium by itself did not affect any of these measures. Thus, lithium pretreatment and muscarinic activation synergistically modulate the hippocampal-prefrontal connectivity. Because these alterations varied with time, oscillatory parameters, and type of synaptic plasticity, our study suggests that lithium influences prefrontal-related circuits through intricate dynamics, informing future experiments on mood disorders.
心境障碍与中脑边缘和额皮质回路的功能失衡有关。作为一种常用的心境稳定剂，锂通过多种生化途径发挥作用，包括那些激活至关重要的海马-前额叶通讯的毒蕈碱型胆碱能受体的途径。因此，在这里我们研究了锂在胆碱能驱动下对前额叶皮层反应的影响。用氨基甲酸乙酯麻醉锂处理的大鼠，并在前额皮质（mPFC）的中间部位植入一个心室套管以进行毒蕈碱激活，在中间海马 CA1 植入一个记录电极和一个刺激电极。在匹鲁卡品作用期间，诱导两种形式的突触可塑性，长时程增强（LTP）或长时程抑制（LTD），并通过局部场电位实时监测。我们发现，锂可减弱皮质 LTP 的毒蕈碱增强作用（<20 分钟），但增强 LTD 维持的毒蕈碱增强作用（>80 分钟）。此外，锂处理促进了 CA1 theta（3-5 Hz）和 mPFC 低γ（30-55 Hz）振荡之间的显著交叉频率耦合。有趣的是，锂本身并不影响这些措施中的任何一个。因此，锂预处理和毒蕈碱激活协同调节海马-前额叶连接。由于这些变化随时间、振荡参数和突触可塑性类型而变化，我们的研究表明，锂通过复杂的动力学影响与前额叶相关的回路，为未来的心境障碍实验提供信息。
