Mid-cervical interneuron networks following high cervical spinal cord injury

Abstract

Spinal interneuron (IN) networks can facilitate respiratory motor recovery after spinal cord injury (SCI). We hypothesized that excitatory synaptic connectivity between INs located immediately caudal to unilateral cervical SCI would be most prevalent in a contra-to ipsilateral direction. Adult rats were studied following chronic C2 spinal cord hemisection (C2Hx) injury. Rats were anesthetized and ventilated and a multi-electrode array was used to simultaneously record INs on both sides of the C4-5 spinal cord. The temporal firing relationship between IN pairs was evaluated using cross-correlation with directionality of synaptic connections inferred based on electrode location. During baseline recordings, the majority of detectable excitatory IN connections occurred in a contra-to-ipsilateral direction. However, acute respiratory stimulation with hypoxia abolished this directionality, while simultaneously increasing the detectable inhibitory connections within the ipsilateral cord. We conclude that propriospinal networks caudal to SCI can display a contralateral-to-ipsilateral directionality of synaptic connections and that these connections are modulated by acute exposure to hypoxia.

Spinal Interneurons as Gatekeepers to Neuroplasticity after Injury or Disease

“…Subsequent studies by the Edgerton group showed that interneurons not only contributed spontaneously to plasticity after injury, but they could also be therapeutically harnessed to improve outcome after partial SCI. This was also more recently shown within respiratory networks (Darlot et al, 2012), where chemogenetic (Satkunendrarajah et al, 2018) or neurochemical (Streeter et al, 2020) stimulation of SpINs can modulate and even improve functional output after SCI. Engineering and transplantation of subsets of SpINs have also been shown to enhance plasticity and functional recovery after SCI (White et al, 2010;Brock et al, 2018;Dulin et al, 2018;Kumamaru et al, 2018;Zholudeva et al, 2018b).…”

LAR inhibitory peptide promotes recovery of diaphragm function and multiple forms of respiratory neural circuit plasticity after cervical spinal cord injury

“…Hemisection of the cervical level 2 (C2) spinal cord from the midline to lateral edge has been used extensively to study respiratory plasticity following SCI ( Bezdudnaya et al, 2017 ; Mantilla et al, 2017 ; Streeter et al, 2020 ). C2 hemisection axotomizes descending bulbospinal pathways originating in the rVRG of the medulla, thereby interrupting their connections to the PhMNs located at cervical levels C3-C5.…”

Closed-Loop, Cervical, Epidural Stimulation Elicits Respiratory Neuroplasticity after Spinal Cord Injury in Freely Behaving Rats

“…Interneuronal (Lane, 2011;Lane et al, 2009;Sandhu et al, 2009) pathways near the phrenic motor nucleus have been suggested to play an important role in respiratory neuroplasticity after spinal cord injury. Additionally, these interneurons may modulate the activity of respiratory motoneurons normally or during conditions of altered respiratory drive (Kirkwood et al, 1993;Streeter et al, 2017;Streeter et al, 2020).…”