Nagaraja Chetan
Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, United States.
IBRO Rep. 2020 Oct 27;9:310-318. doi: 10.1016/j.ibror.2020.10.005. eCollection 2020 Dec.
Early in the postnatal period, motoneuron axon stimulation can excite motor networks in the spinal cord. Here we tested if these excitatory effects changed across early postnatal development up to postnatal day (P) 24 by when mice are capable of weight-bearing locomotion and locomotor networks are considered functionally mature. This was accomplished in the isolated spinal cord preparation using ventral root evoked entrainment of disinhibited bursts. Ventral root evoked entrainment was defined and characterized over the first 2 weeks of postnatal development, and was found to decline over this period, but entrainment could still be detected in mice as old as P24. Disinhibited bursting could be elicited, and dorsal root evoked entrainment could be recorded as late as P39 and remained unchanged in effectiveness, suggesting that poor tissue viability may not be the cause of the decline in ventral root evoked entrainment. Pharmacological experiments performed on younger animals established that dopamine D2 receptor antagonists and mGluR1 agonists both enhanced ventral root evoked entrainment. In conclusion, the motoneuronal inputs to spinal motor networks via the excitatory pathway is modulated by dopamine and metabotropic glutamate receptors and may be under powerful inhibitory control, which may explain why there is a developmental decline in entrainment.
在出生后的早期阶段,运动神经元轴突刺激可兴奋脊髓中的运动网络。在此,我们测试了这些兴奋性效应在出生后早期发育直至出生后第24天(P24)是否发生变化,到这个时候小鼠能够进行负重运动且运动网络被认为在功能上已成熟。这是在离体脊髓标本中通过腹根诱发的去抑制爆发的夹带作用来完成的。在出生后发育的前两周对腹根诱发的夹带作用进行了定义和表征,发现在此期间其有所下降,但在P24的小鼠中仍可检测到夹带作用。去抑制爆发可被诱发,并且背根诱发的夹带作用最晚在P39时仍可记录到且有效性保持不变,这表明组织活力不佳可能不是腹根诱发夹带作用下降的原因。对较年幼动物进行的药理学实验表明,多巴胺D2受体拮抗剂和代谢型谷氨酸受体1激动剂均可增强腹根诱发的夹带作用。总之,通过兴奋性通路对脊髓运动网络的运动神经元输入受多巴胺和代谢型谷氨酸受体调节,并且可能受到强大的抑制性控制,这可能解释了为什么夹带作用在发育过程中会下降。