scholarly journals Spinal microcircuits comprising dI3 interneurons are necessary for motor functional recovery following spinal cord transection

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Tuan V Bui ◽  
Nicolas Stifani ◽  
Turgay Akay ◽  
Robert M Brownstone
Keyword(s):  
Spinal Cord ◽  
Functional Recovery ◽  
Motor System ◽  
Motor Training ◽  
Prediction Errors ◽  
Spinal Interneurons ◽  
Motor Activities ◽  
Afferent Inputs ◽  
To Receive ◽  
Sensory Prediction

The spinal cord has the capacity to coordinate motor activities such as locomotion. Following spinal transection, functional activity can be regained, to a degree, following motor training. To identify microcircuits involved in this recovery, we studied a population of mouse spinal interneurons known to receive direct afferent inputs and project to intermediate and ventral regions of the spinal cord. We demonstrate that while dI3 interneurons are not necessary for normal locomotor activity, locomotor circuits rhythmically inhibit them and dI3 interneurons can activate these circuits. Removing dI3 interneurons from spinal microcircuits by eliminating their synaptic transmission left locomotion more or less unchanged, but abolished functional recovery, indicating that dI3 interneurons are a necessary cellular substrate for motor system plasticity following transection. We suggest that dI3 interneurons compare inputs from locomotor circuits with sensory afferent inputs to compute sensory prediction errors that then modify locomotor circuits to effect motor recovery.

Multiple Effects of Serotonin and Acetylcholine on Hyperpolarization-Activated Inward Current in Locomotor Activity-Related Neurons in Cfos-EGFP Mice

2010 ◽  
Vol 104 (1) ◽  
pp. 366-381 ◽  
Author(s):  
Yue Dai ◽  
Larry M. Jordan
Keyword(s):  
Spinal Cord ◽  
Motor System ◽  
Reversal Potential ◽  
Rhythmic Activity ◽  
Maximal Conductance ◽  
Inward Current ◽  
Spinal Interneurons ◽  
Whole Cell Patch Clamp ◽  
Activation Rate ◽  
Maximal Activation

Hyperpolarization-activated inward current ( Ih) has been shown to be involved in production of bursting during various forms of rhythmic activity. However, details of Ih in spinal interneurons related to locomotion remain unknown. Using Cfos-EGFP transgenic mice (P6–P12) we are able to target the spinal interneurons activated by locomotion. Following a locomotor task, whole cell patch-clamp recordings were obtained from ventral EGFP+ neurons in spinal cord slices (T13–L4, 200–250 μm). Ih was found in 51% of EGFP+ neurons ( n = 149) with almost even distribution in lamina VII (51%), VIII (47%), and X (55%). Ih could be blocked by ZD7288 (10–20 μM) or cesium (1–1.5 mM) but was insensitive to barium (2–2.5 mM). Ih activated at −80.1 ± 9.2 mV with half-maximal activation −95.5 ± 13.3 mV, activation rate 10.0 ± 3.2 mV, time constant 745 ± 501 ms, maximal conductance 1.0 ± 0.7 nS, and reversal potential −34.3 ± 3.6 mV. 5-HT (15–20 μM) and ACh (20–30 μM) produced variable effects on Ih. 5-HT increased Ih in 43% of EGFP+ neurons ( n = 37), decreased Ih in 24%, and had no effect on Ih in 33% of the neurons. ACh decreased Ih in 67% of EGFP+ neurons ( n = 18) with unchanged Ih in 33% of the neurons. This study characterizes the Ih in locomotor-related interneurons and is the first to demonstrate the variable effects of 5-HT and ACh on Ih in rodent spinal interneurons. The finding of 5-HT and ACh-induced reduction of Ih in EGFP+ neurons suggests a novel mechanism that the motor system could use to limit the participation of certain neurons in locomotion.

The Translesional Spinal Network and Its Reorganization after Spinal Cord Injury

2020 ◽  
pp. 107385842096627 ◽  
Author(s):  
Petr Krupa ◽  
Ahad M. Siddiqui ◽  
Peter J. Grahn ◽  
Riazul Islam ◽  
Bingkun K. Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Research ◽  
Functional Recovery ◽  
Motor Training ◽  
Motor Functions ◽  
Sensory Inputs ◽  
Cord Injury ◽  
Spinal Network ◽  
Motor Signals

Evidence from preclinical and clinical research suggest that neuromodulation technologies can facilitate the sublesional spinal networks, isolated from supraspinal commands after spinal cord injury (SCI), by reestablishing the levels of excitability and enabling descending motor signals via residual connections. Herein, we evaluate available evidence that sublesional and supralesional spinal circuits could form a translesional spinal network after SCI. We further discuss evidence of translesional network reorganization after SCI in the presence of sensory inputs during motor training. In this review, we evaluate potential mechanisms that underlie translesional circuitry reorganization during neuromodulation and rehabilitation in order to enable motor functions after SCI. We discuss the potential of neuromodulation technologies to engage various components that comprise the translesional network, their functional recovery after SCI, and the implications of the concept of translesional network in development of future neuromodulation, rehabilitation, and neuroprosthetics technologies.

scholarly journals An injury-induced serotonergic neuron subpopulation contributes to axon regrowth and function restoration after spinal cord injury in zebrafish

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chun-Xiao Huang ◽  
Yacong Zhao ◽  
Jie Mao ◽  
Zhen Wang ◽  
Lulu Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Spinal Neurons ◽  
Knock Out ◽  
Spinal Interneurons ◽  
Axonal Regrowth ◽  
Robust Model ◽  
Cord Injury ◽  
And Function

AbstractSpinal cord injury (SCI) interrupts long-projecting descending spinal neurons and disrupts the spinal central pattern generator (CPG) that controls locomotion. The intrinsic mechanisms underlying re-wiring of spinal neural circuits and recovery of locomotion after SCI are unclear. Zebrafish shows axonal regeneration and functional recovery after SCI making it a robust model to study mechanisms of regeneration. Here, we use a two-cut SCI model to investigate whether recovery of locomotion can occur independently of supraspinal connections. Using this injury model, we show that injury induces the localization of a specialized group of intraspinal serotonergic neurons (ISNs), with distinctive molecular and cellular properties, at the injury site. This subpopulation of ISNs have hyperactive terminal varicosities constantly releasing serotonin activating 5-HT1B receptors, resulting in axonal regrowth of spinal interneurons. Axon regrowth of excitatory interneurons is more pronounced compared to inhibitory interneurons. Knock-out of htr1b prevents axon regrowth of spinal excitatory interneurons, negatively affecting coordination of rostral-caudal body movements and restoration of locomotor function. On the other hand, treatment with 5-HT1B receptor agonizts promotes functional recovery following SCI. In summary, our data show an intraspinal mechanism where a subpopulation of ISNs stimulates axonal regrowth resulting in improved recovery of locomotor functions following SCI in zebrafish.

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