Park Anthony, Li Ying, Masri Radi, Keller Asaf
Program in Neuroscience and Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland; and.
Department of Endodontics, Periodontics and Prosthodontics, University of Maryland Baltimore, School of Dentistry, Baltimore, Maryland.
J Neurophysiol. 2017 Jul 1;118(1):507-519. doi: 10.1152/jn.00862.2016. Epub 2017 Mar 22.
The posterior nucleus of thalamus (PO) is a higher-order nucleus involved in sensorimotor processing, including nociception. An important characteristic of PO is its wide range of activity profiles that vary across states of arousal, thought to underlie differences in somatosensory perception subject to attention and degree of consciousness. Furthermore, PO loses the ability to downregulate its activity level in some forms of chronic pain, suggesting that regulatory mechanisms underlying the normal modulation of PO activity may be pathologically altered. However, the mechanisms responsible for regulating such a wide dynamic range of activity are unknown. Here, we test a series of hypotheses regarding the function of several presynaptic receptors on both GABAergic and glutamatergic afferents targeting PO in mouse, using acute slice electrophysiology. We found that presynaptic GABA receptors are present on both GABAergic and glutamatergic terminals in PO, but only those on GABAergic terminals are tonically active. We also found that release from GABAergic terminals, but not glutamatergic terminals, is suppressed by cholinergic activation and that a subpopulation of GABAergic terminals is regulated by cannabinoids. Finally, we discovered the presence of tonic currents mediated by extrasynaptic GABA receptors in PO that are heterogeneously distributed across the nucleus. Thus we demonstrate that multiple regulatory mechanisms concurrently exist in PO, and we propose that regulation of inhibition, rather than excitation, is the more consequential mechanism by which PO activity can be regulated. The posterior nucleus of thalamus (PO) is a key sensorimotor structure, whose activity is tightly regulated by inhibition from several nuclei. Maladaptive plasticity in this inhibition leads to severe pathologies, including chronic pain. We reveal here, for the first time in PO, multiple regulatory mechanisms that modulate synaptic transmission within PO. These findings may lead to targeted therapies for chronic pain and other disorders.
丘脑后核（PO）是一个参与感觉运动处理（包括伤害感受）的高级核团。PO的一个重要特征是其广泛的活动模式，这些模式在觉醒状态下会有所不同，被认为是受注意力和意识程度影响的体感感知差异的基础。此外，在某些形式的慢性疼痛中，PO失去了下调其活动水平的能力，这表明PO活动正常调节的潜在机制可能发生了病理性改变。然而，负责调节如此广泛动态活动范围的机制尚不清楚。在这里，我们使用急性脑片电生理学方法，测试了一系列关于几种突触前受体在靶向小鼠PO的GABA能和谷氨酸能传入神经上的功能的假设。我们发现，突触前GABA受体存在于PO的GABA能和谷氨酸能终末上，但只有GABA能终末上的那些受体具有紧张性活性。我们还发现，胆碱能激活可抑制GABA能终末的释放，但不能抑制谷氨酸能终末的释放，并且GABA能终末的一个亚群受大麻素调节。最后，我们发现PO中存在由突触外GABA受体介导的紧张性电流，这些电流在整个核内呈异质性分布。因此，我们证明PO中同时存在多种调节机制，并且我们提出，对抑制的调节而非兴奋的调节是调节PO活动的更重要机制。丘脑后核（PO）是一个关键的感觉运动结构，其活动受到几个核团的抑制的严格调节。这种抑制中的适应不良可塑性会导致严重的病理状况，包括慢性疼痛。我们在此首次揭示了PO中调节其内部突触传递的多种调节机制。这些发现可能会为慢性疼痛和其他疾病带来有针对性的治疗方法。
