Plasticity of connections underlying locomotor recovery after central and/or peripheral lesions in the adult mammals

Abstract

This review discusses some aspects of plasticity of connections after spinal injury in adult animal models as a basis for functional recovery of locomotion. After reviewing some pitfalls that must be avoided when claiming functional recovery and the importance of a conceptual framework for the control of locomotion, locomotor recovery after spinal lesions, mainly in cats, is summarized. It is concluded that recovery is partly due to plastic changes within the existing spinal locomotor networks. Locomotor training appears to change the excitability of simple reflex pathways as well as more complex circuitry. The spinal cord possesses an intrinsic capacity to adapt to lesions of central tracts or peripheral nerves but, as a rule, adaptation to lesions entails changes at both spinal and supraspinal levels. A brief summary of the spinal capacity of the rat, mouse and human to express spinal locomotor patterns is given, indicating that the concepts derived mainly from work in the cat extend to other adult mammals. It is hoped that some of the issues presented will help to evaluate how plasticity of existing connections may combine with and potentiate treatments designed to promote regeneration to optimize remaining motor functions.

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

“…The onset for return of spontaneous function in both humans and animals after complete SCI could be due to the restoration of motoneuron excitability by constitutive expression of 5-HT2C receptors [11,12]. Additionally, adaptations in polysynaptic flexor reflexes involved in locomotor circuits [6,13] and synaptic rearrangements may contribute to this first phase of recovery as well [14]. The temporal differences in the spontaneous functional return onset may be due to the relatively higher metabolism of rodents.…”

Prominent Role of the Spinal Central Pattern Generator in the Recovery of Locomotion after Partial Spinal Cord Injuries

“…After a complete chronic spinal transection, the spinal locomotor CPG is undoubtedly critical for the expression of locomotion, which must involve appropriate reorganization of the spinal circuitry (Frigon and Rossignol, 2006;Rossignol, 2006). In "normal" cats (i.e., without a previous partial spinal lesion as is the case here), the expression of locomotion after a complete spinalization nor- mally takes 2-3 weeks of treadmill training without pharmacological aids (Barbeau and Rossignol, 1987).…”

“…However, locomotor training greatly facilitated the recovery of locomotion after the partial spinal lesion (Lovely et al, 1986(Lovely et al, , 1990Barbeau and Rossignol, 1987;Bélanger et al, 1988Bélanger et al, , 1996Wernig and Muller, 1992;Dietz et al, 1994;de Leon et al, 1998;Van de Crommert et al, 1998;Harkema, 2001;Sullivan et al, 2002;Barbeau and Visintin, 2003;Rossignol, 2006;Plummer et al, 2007). Comparing locomotor abilities in a trained and untrained cat at the same time after the partial lesion showed that treadmill training promoted an earlier recovery of locomotion (Fig.…”

“…The importance of this CPG is made clear by the observation that after a complete spinal section at T13, kittens and adult cats recover hindlimb locomotion on a treadmill (Forssberg et al, 1980a,b;Barbeau and Rossignol, 1987;Lovely et al, 1990). The second control element are the sensory feedback generating phasic signals to the CPG allowing adaptation to real environments made of uneven terrains and obstacles (Rossignol, 2006;Rossignol et al, 2006). Finally, descending pathways (third control element) from the telencephalon and the brainstem are essential in providing start-stop signals, steering, coordination, posture, anticipatory adjustments and also neurochemical drive to the cord (Rossignol, 1996).…”

“…However, after bilateral dorsolateral or ventrolateral lesions, or lateral hemisections at low thoracic levels, cats can recover voluntary quadrupedal locomotion albeit with some deficits specific to each lesion (Kato et al, 1984;Gorska et al, 1993;Helgren and Goldberger, 1993;Jiang and Drew, 1996;Kuhtz-Buschbeck et al, 1996;Brustein and Rossignol, 1998;Rossignol et al, 1999). The recovery of locomotion after partial lesions may depend on multiple cooperative mechanisms that can be regrouped under the general heading of neuroplasticity (Wolpaw and Tennissen, 2001;Nudo, 2006;Rossignol, 2006). After partial SCI, the regeneration of damaged fibers and/or sprouting of undamaged fibers may contribute to recovery (Fouad et al, 2001;Raineteau and Schwab, 2001; Raineteau et al, 2002;Bareyre et al, 2004; Ballermann and Fouad, 2006).…”