Carter David A, Guo Haoyao, Thek Kimberly R, Connelly Angela A, Bassi Jaspreet K, Fong Angelina Y, Allen Andrew M, McDougall Stuart J
Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
Florey Institute of Neuroscience and Mental Health, Victoria 3010, Australia.
Auton Neurosci. 2025 Aug;260:103305. doi: 10.1016/j.autneu.2025.103305. Epub 2025 May 29.
Autonomic reflexes are modified during development or in response to specific physiological challenges and disease. One modulating region is the hypothalamic paraventricular nucleus (PVN), whose neurons project to the nucleus of the solitary tract (NTS) to modulate viscerosensory input. Yet the neural circuitry by which this is achieved remains ill-defined. Adeno-associated virus was injected into the hypothalamus of TH-GFP or angiotensin type 1A receptor (ATR)-GFP mice to drive channel rhodopsin 2 (ChR2) expression. Whole-cell recordings of NTS neurons in close proximity to labelled hypothalamic efferents were made in horizontal slices of the brainstem, allowing activation of both hypothalamic and viscerosensory inputs. Most neurons recorded did not exhibit ChR2-mediated responses, despite extensive hypothalamic axon/terminal labelling. In some NTS neurons, ChR2-mediated stimulation of hypothalamic efferents elicited glutamatergic, AMPA receptor mediated excitatory postsynaptic currents (ChR2-EPSCs). Responsive NTS neurons included both 2nd, and higher, order neurons and ATR and few TH expressing neurons. All ChR2-EPSCs tested were blocked by TTX. Some TTX blocked ChR2-EPSCs could be recovered with the co-application 4AP, confirming monosynaptic connection between hypothalamic and NTS neurons. Superimposition of convergent inputs from hypothalamic and viscerosensory efferents resulted in summated EPSCs that would likely increase throughput probability of the viscerosensory signals at NTS neurons. The neural link between the hypothalamus and NTS comprises discreet glutamatergic input, including to TH positive and ATR expressing NTS neurons.
自主反射在发育过程中或对特定生理挑战及疾病作出反应时会发生改变。其中一个调节区域是下丘脑室旁核（PVN），其神经元投射到孤束核（NTS）以调节内脏感觉输入。然而，实现这一调节的神经回路仍不清楚。将腺相关病毒注射到TH-GFP或血管紧张素1A型受体（ATR）-GFP小鼠的下丘脑，以驱动通道视紫红质2（ChR2）表达。在脑干水平切片中对紧邻标记的下丘脑传出纤维的NTS神经元进行全细胞记录，从而能够激活下丘脑和内脏感觉输入。尽管下丘脑轴突/终末有广泛标记，但大多数记录的神经元并未表现出ChR2介导的反应。在一些NTS神经元中，ChR2介导的下丘脑传出纤维刺激引发了谷氨酸能、AMPA受体介导的兴奋性突触后电流（ChR2-EPSCs）。有反应的NTS神经元包括二级及更高级别的神经元以及ATR和少数表达TH的神经元。所有测试的ChR2-EPSCs都被TTX阻断。一些被TTX阻断的ChR2-EPSCs可通过共同应用4AP恢复，证实了下丘脑和NTS神经元之间的单突触连接。下丘脑和内脏感觉传出纤维的汇聚输入叠加导致EPSCs总和，这可能会增加NTS神经元处内脏感觉信号的通过概率。下丘脑和NTS之间的神经联系包括离散的谷氨酸能输入，包括对表达TH阳性和ATR的NTS神经元的输入。
