Santin Marie des Neiges, Tempier Nicolas, Belaid Hayat, Zenoni Matthieu, Dumas Sylvie, Wallén-Mackenzie Åsa, Bardinet Eric, Destrieux Christophe, François Chantal, Karachi Carine
Sorbonne Université, Institut du Cerveau-Paris Brain Institute- ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière, 75013, Paris, France.
Service de Neurochirurgie, Hôpital Fondation Adolphe de Rothschild, 29 rue Manin, Paris, France.
Brain Struct Funct. 2023 Nov;228(8):1977-1992. doi: 10.1007/s00429-023-02691-2. Epub 2023 Sep 5.
Effective neural stimulation for the treatment of severe psychiatric disorders needs accurate characterisation of surgical targets. This is especially true for the medial subthalamic region (MSR) which contains three targets: the anteromedial STN for obsessive compulsive disorder (OCD), the medial forebrain bundle (MFB) for depression and OCD, and the "Sano triangle" for pathological aggressiveness. Blocks containing the subthalamic area were obtained from two human brains. After obtaining 11.7-Tesla MRI, blocks were cut in regular sections for immunohistochemistry. Fluorescent in situ hybridisation was performed on the macaque MSR. Electron microscopic observation for synaptic specialisation was performed on human and macaque subthalamic fresh samples. Images of human brain sections were reconstructed in a cryoblock which was registered on the MRI and histological slices were then registered. The STN contains glutamatergic and fewer GABAergic neurons and has no strict boundary with the adjacent MSR. The anteromedial STN has abundant dopaminergic and serotoninergic innervation with very sparse dopaminergic neurons. The MFB is composed of dense anterior dopaminergic and posterior serotoninergic fibres, and fewer cholinergic and glutamatergic fibres. Medially, the Sano triangle presumably contains orexinergic terminals from the hypothalamus, and neurons with strong nuclear oestrogen receptor-alpha staining with a decreased anteroposterior and mediolateral gradient of staining. These findings provide new insight regarding MSR cells and their fibre specialisation, forming a transition zone between the basal ganglia and the limbic systems. Our 3D reconstruction enabled us to visualize the main histological features of the three targets which should enable better targeting and understanding of neuromodulatory stimulation results in severe psychiatric conditions.
有效的神经刺激用于治疗严重精神疾病需要准确界定手术靶点。对于包含三个靶点的内侧丘脑底区域（MSR）而言尤其如此，这三个靶点分别是：用于治疗强迫症（OCD）的前内侧丘脑底核（STN）、用于治疗抑郁症和强迫症的内侧前脑束（MFB）以及用于治疗病理性攻击行为的“佐野三角”。从两例人脑获取了包含丘脑底区域的脑块。获取11.7特斯拉的磁共振成像（MRI）后，将脑块切成常规切片用于免疫组织化学检测。对猕猴的MSR进行了荧光原位杂交。对人和猕猴丘脑底新鲜样本进行了突触特化的电子显微镜观察。在冷冻块中重建人脑切片图像，该冷冻块已与MRI配准，然后将组织学切片进行配准。STN包含谷氨酸能神经元且GABA能神经元较少，与相邻的MSR没有严格界限。前内侧STN有丰富的多巴胺能和5-羟色胺能神经支配，但多巴胺能神经元非常稀疏。MFB由密集的前部多巴胺能纤维和后部5-羟色胺能纤维组成，胆碱能和谷氨酸能纤维较少。在内侧，佐野三角可能包含来自下丘脑的食欲素能终末，以及核雌激素受体α染色强烈的神经元，其染色的前后和内外侧梯度降低。这些发现为MSR细胞及其纤维特化提供了新的见解，形成了基底神经节和边缘系统之间的过渡区。我们的三维重建使我们能够可视化这三个靶点的主要组织学特征，这应该有助于在严重精神疾病中更好地进行靶点定位并理解神经调节刺激的结果。
