Yetnikoff Leora, Cheng Anita Y, Lavezzi Heather N, Parsley Kenneth P, Zahm Daniel S
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri.
J Comp Neurol. 2015 Nov 1;523(16):2426-56. doi: 10.1002/cne.23797. Epub 2015 Jun 10.
Profound inhibitory control exerted on midbrain dopaminergic neurons by the lateral habenula (LHb), which has mainly excitatory outputs, is mediated by the GABAergic rostromedial tegmental nucleus (RMTg), which strongly innervates dopaminergic neurons in the ventral midbrain. Early reports indicated that the afferent connections of the RMTg, excepting its very strong LHb inputs, do not differ appreciably from those of the ventral tegmental area (VTA). Presumably, however, the RMTg contributes more to behavioral synthesis than to simply invert the valence of the excitatory signal coming from the LHb. Therefore, the present study was done to directly compare the inputs to the RMTg and VTA and, in deference to its substantial involvement with this circuitry, the LHb was also included in the comparison. Data indicated that, while the afferents of the RMTg, VTA, and LHb do originate within the same large pool of central nervous system (CNS) structures, each is also related to structures that project more strongly to it than to the others. The VTA gets robust input from ventral striatopallidum and extended amygdala, whereas RMTg biased inputs arise in structures with a more direct impact on motor function, such as deep layers of the contralateral superior colliculus, deep cerebellar and several brainstem nuclei, and, via a relay in the LHb, the entopeduncular nucleus. Input from the ventral pallidal-lateral preoptic-lateral hypothalamus continuum is strong in the RMTg and VTA and dominant in the LHb. Axon collateralization was also investigated, providing additional insights into the organization of the circuitry of this important triad of structures.
外侧缰核(LHb)对中脑多巴胺能神经元施加了深度抑制性控制,而外侧缰核主要具有兴奋性输出,这种控制是由γ-氨基丁酸能的嘴内侧被盖核(RMTg)介导的,该核强烈支配腹侧中脑的多巴胺能神经元。早期报告表明,RMTg的传入连接,除了其非常强的LHb输入外,与腹侧被盖区(VTA)的传入连接没有明显差异。然而,据推测,RMTg对行为整合的贡献更多,而不仅仅是反转来自LHb的兴奋性信号的效价。因此,本研究旨在直接比较RMTg和VTA的输入,并且鉴于LHb大量参与该神经回路,也将其纳入比较。数据表明,虽然RMTg、VTA和LHb的传入神经确实起源于同一个大的中枢神经系统(CNS)结构池,但每个结构也与比其他结构更强烈地投射到它的结构相关。VTA从腹侧纹状体苍白球和扩展杏仁核获得强大的输入,而RMTg的偏向性输入则来自对运动功能有更直接影响的结构,如对侧上丘深层、小脑深部和几个脑干核,并且通过LHb中的一个中继,来自内苍白球核。来自腹侧苍白球-外侧视前区-外侧下丘脑连续体的输入在RMTg和VTA中很强,在LHb中占主导地位。还研究了轴突侧支化,为这一重要的三联结构的神经回路组织提供了额外的见解。