Melo-Thomas Liana, Tacken Lars, Richter Nicole, Almeida Davina, Rapôso Catarina, de Melo Silvana Regina, Thomas Uwe, de Paiva Yara Bezerra, Medeiros Priscila, Coimbra Norberto C, Schwarting Rainer
Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Gutenbergstr. 18, D-35032, Marburg, Germany.
Center for Mind, Brain, and Behavior (CMBB), Hans-Meerwein-Straße 6, 35032, Marburg, Germany.
eNeuro. 2022 Jul 11;9(4). doi: 10.1523/ENEURO.0076-22.2022.
After unilateral lesion of the medial forebrain bundle (MFB) by 6-OHDA rats exhibit lateralized deficits in spontaneous behavior or apomorphine-induced rotations. We investigated whether such lateralization is attenuated by either deep brain stimulation (DBS) or glutamatergic neurotransmission in the inferior colliculus (IC) of Wistar rats. Intracollicular DBS did not affect spontaneous lateralization but attenuated apomorphine-induced rotations. Spontaneous lateralization disappeared after both glutamatergic antagonist MK-801 or the agonist NMDA microinjected in the IC. Apomorphine-induced rotations were potentiated by MK-801 but were not affected by NMDA intracollicular microinjection. After injecting a bidirectional neural tract tracer into the IC, cell bodies and/or axonal fibers were found in the periaqueductal gray, superior colliculus, substantia nigra, cuneiform nucleus and pedunculo-pontine tegmental nucleus, suggesting the involvement of these structures in the motor improvement after IC manipulation. Importantly, the side of the IC microinjection regarding the lesion (ipsi- or contralateral) is particularly important and this effect may not involve the neostriatum directly.The inferior colliculus, usually viewed as an auditory structure, when properly manipulated may counteract motor deficits in Parkinsonian rats. Indeed, the present study showed that 30 Hz deep brain stimulation or glutamatergic neural network in the inferior colliculus reduced body asymmetry induced by medial forebrain bundle unilateral 6-OHDA lesion in rats, an animal model of Parkinsonism. Understanding how glutamatergic mechanisms in the inferior colliculus influence motor control, classically attributed to the basal nuclei circuitry, could be useful in the development of new therapeutics to treat Parkinson's disease and other motor disorders.
通过6-羟基多巴胺对内侧前脑束（MFB）进行单侧损伤后，大鼠在自发行为或阿扑吗啡诱导的旋转中表现出偏侧化缺陷。我们研究了在Wistar大鼠的下丘（IC）中，深部脑刺激（DBS）或谷氨酸能神经传递是否会减弱这种偏侧化。下丘内DBS不影响自发偏侧化，但可减弱阿扑吗啡诱导的旋转。在下丘内注射谷氨酸能拮抗剂MK-801或激动剂NMDA后，自发偏侧化消失。MK-801增强了阿扑吗啡诱导的旋转，但下丘内注射NMDA对其没有影响。向IC注射双向神经束示踪剂后，在导水管周围灰质、上丘、黑质、楔形核和脑桥脚被盖核中发现了细胞体和/或轴突纤维，提示这些结构参与了IC操作后的运动改善。重要的是，IC微注射相对于损伤的侧别（同侧或对侧）尤为重要，且这种效应可能不直接涉及新纹状体。下丘通常被视为听觉结构，当进行适当操作时，可能会抵消帕金森病大鼠的运动缺陷。事实上，本研究表明，30Hz的深部脑刺激或下丘中的谷氨酸能神经网络可减少大鼠内侧前脑束单侧6-羟基多巴胺损伤（一种帕金森病动物模型）所诱导的身体不对称。了解下丘中的谷氨酸能机制如何影响传统上归因于基底核回路的运动控制，可能有助于开发治疗帕金森病和其他运动障碍的新疗法。
