Compensatory plasticity restores locomotion after chronic removal of descending projections

Abstract

Homeostatic plasticity is an important attribute of neurons and their networks, enabling functional recovery after perturbation. Furthermore, the directed nature of this plasticity may hold a key to the restoration of locomotion after spinal cord injury. Here we studied the recovery of crawling in the leech Hirudo verbana after descending cephalic fibers were surgically separated from crawl central pattern generators shown previously to be regulated by dopamine. We observed that immediately after nerve cord transection leeches were unable to crawl, but remarkably, after a day to weeks, animals began to show elements of crawling and intersegmental coordination. Over a similar time course, excessive swimming due to the loss of descending inhibition returned to control levels. Additionally, removal of the brain did not prevent crawl recovery, indicating that connectivity of severed descending neurons was not essential. After crawl recovery, a subset of animals received a second transection immediately below the anterior-most ganglion remaining. Similar to their initial transection, a loss of crawling with subsequent recovery was observed. These data, in recovered individuals, support the idea that compensatory plasticity directly below the site of injury is essential for the initiation and coordination of crawling. We maintain that the leech provides a valuable model to understand the neural mechanisms underlying locomotor recovery after injury because of its experimental accessibility, segmental organization, and dependence on higher-order control involved in the initiation, modulation, and coordination of locomotor behavior.

Functional Recovery of a Locomotor Network after Injury: Plasticity beyond the Central Nervous System

“…Several studies have reported that motor recovery is realized via the regrowth and reconnection of neural fibers across the site of injury ( Parker, 2017 ; Rasmussen and Sagasti, 2017 ; Joven and Simon, 2018 ). In contrast, and somewhat more enigmatic, are findings that the restoration of motor function can occur without the successful reconnection of damaged central pathways ( Edgerton et al, 2004 ; Sakurai and Katz, 2009 ; Rossignol and Frigon, 2011 ; Harley et al, 2015 ). Thus, a critical problem in the neurosciences is to understand how a neural system can functionally recover when its higher-order descending inputs, critical for action selection and movement, are permanently lost.…”

“…For many decades, the medicinal leech has served as a well-established model system for revealing the network and cellular bases of behavior, including swimming and crawling ( Kristan et al, 2005 ). We have shown previously that leeches can recover their ability to crawl after a complete transection of the ventral nerve cord below the brain, which serves to remove identified descending fibers normally necessary for crawl initiation and coordination ( Harley et al, 2015 ). Crawling is the terrestrial form of locomotion and is defined, at its core, as alternating elongations and contractions of the body with associated attachments of the anterior and posterior muscular suckers ( Stern-Tomlinson et al, 1986 ).…”

“…After complete transection (i.e., injury) of the CNS, leeches immediately lose their ability to generate crawl-specific movements ( Harley et al, 2015 ), presumably because R3b-1 signaling is interrupted. Several days later, however, rudimentary crawl-like movements begin to be expressed, although proper intersegmental coordination is lacking.…”

“…After several weeks, coordinated crawling movements are reestablished and overt crawling is difficult to distinguish from uninjured animals. This crawl recovery is not reliant on the regrowth and reconnectivity of the damaged CNS fibers; in fact, additional experimental efforts have been made to prevent reconnections from forming ( Harley et al, 2015 ). Thus, some type of homeostatic plasticity must be in play to enable the 21 independent crawl CPGs to regain their coordination (i.e., normal phase relationships) with each other.…”

Consequences of acute and long-term removal of neuromodulatory input on the episodic gastric rhythm of the crabCancer borealis

“…When the spinal cord is severed action potential propagation is lost through the lesion, and these isolated networks may develop pathological, spastic activity patterns that can cause significant difficulties for the patient (Beauparlant et al 2013;Little et al 1989). Recent work in other central pattern generator (CPG) systems has investigated how proper function might be restored after similar injuries and how underlying neuronal variability affects individual vulnerability to the loss of modulatory input (Harley et al 2015;Sakurai et al 2014;Sakurai and Katz 2009). …”