Laboratory of Neurophysiology, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida MSD 2080, Malta.
Neuroscience Division, School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
Int J Mol Sci. 2020 Apr 15;21(8):2734. doi: 10.3390/ijms21082734.
The motor thalamus (MTh) plays a crucial role in the basal ganglia (BG)-cortical loop in motor information codification. Despite this, there is limited evidence of MTh functionality in normal and Parkinsonian conditions. To shed light on the functional properties of the MTh, we examined the effects of acute and chronic dopamine (DA) depletion on the neuronal firing of MTh neurons, cortical/MTh interplay and MTh extracellular concentrations of glutamate (GLU) and gamma-aminobutyric acid (GABA) in two states of DA depletion: acute depletion induced by the tetrodotoxin (TTX) and chronic denervation obtained by 6-hydroxydopamine (6-OHDA), both infused into the medial forebrain bundle (MFB) in anesthetized rats. The acute TTX DA depletion caused a clear-cut reduction in MTh neuronal activity without changes in burst content, whereas the chronic 6-OHDA depletion did not modify the firing rate but increased the burst firing. The phase correlation analysis underscored that the 6-OHDA chronic DA depletion affected the MTh-cortical activity coupling compared to the acute TTX-induced DA depletion state. The TTX acute DA depletion caused a clear-cut increase of the MTh GABA concentration and no change of GLU levels. On the other hand, the 6-OHDA-induced chronic DA depletion led to a significant reduction of local GABA and an increase of GLU levels in the MTh. These data show that MTh is affected by DA depletion and support the hypothesis that a rebalancing of MTh in the chronic condition counterbalances the profound alteration arising after acute DA depletion state.
运动丘脑（MTh）在基底神经节（BG）-皮层回路中对运动信息编码起着至关重要的作用。尽管如此，关于 MTh 在正常和帕金森病状态下的功能仍缺乏证据。为了阐明 MTh 的功能特性，我们研究了急性和慢性多巴胺（DA）耗竭对 MTh 神经元放电、皮质/MTh 相互作用以及谷氨酸（GLU）和γ-氨基丁酸（GABA）在两种 DA 耗竭状态下的 MTh 细胞外浓度的影响：急性耗竭由河豚毒素（TTX）诱导，慢性去神经由 6-羟基多巴胺（6-OHDA）引起，均注入麻醉大鼠的内侧前脑束（MFB）。急性 TTX 耗竭 DA 导致 MTh 神经元活动明显减少，而不改变爆发内容，而慢性 6-OHDA 耗竭不改变放电率，但增加爆发放电。相位相关分析强调，与急性 TTX 诱导的 DA 耗竭状态相比，慢性 6-OHDA 耗竭 DA 会影响 MTh-皮质活动偶联。急性 TTX 耗竭 DA 导致 MTh GABA 浓度明显增加，GLU 水平不变。另一方面，6-OHDA 诱导的慢性 DA 耗竭导致 MTh 中局部 GABA 减少和 GLU 水平增加。这些数据表明，MTh 受到 DA 耗竭的影响，并支持这样一种假设，即慢性状态下 MTh 的再平衡平衡了急性 DA 耗竭状态后出现的深刻改变。
