Pharmacological Activation and Modulation of the Central Pattern Generator for Locomotion in the Cat^a

Abstract

Pharmacological agents have been shown to be capable of inducing a pattern of rhythmic activity recorded in muscle nerves or motoneurons of paralyzed spinal cats that closely resembles the locomotor pattern seen in intact cats. Further work, using intraperitoneal or intrathecal injections, suggests that different neurotransmitters may be involved in various aspects of locomotor control, e.g., initiation and modulation of the pattern. Although precursors, agonists or the neurotransmitters themselves of several systems have been investigated (noradrenergic, dopaminergic, serotonergic, glutamatergic), the noradrenergic system seems the most efficient in triggering locomotion in complete spinal cats, with the alpha-2 agonists (clonidine, tizanidine, oxymetazoline) being more potent than the alpha-1 agonist, methoxamine. Moreover, the potency of the drugs may depend on the time of application after the spinal lesion. In chronic spinal cats capable of spontaneous walking on hindlimbs on the treadmill, all neurotransmitters appear to exert distinct recognizable effects on the locomotor pattern. More recent work also suggests that the effects of drugs may differ significantly depending on the type of spinal lesion. For instance, clonidine further reduces the level of weight support during quadrupedal locomotion of cats with lesions of the ventral-ventrolateral funiculi, possibly due to an interference of clonidine with essential compensatory mechanisms used by these animals to walk. Such considerations as the type of drugs, type of lesions, and the time after the lesion will be important for future studies in spinal cord injured patients.

Inhibiting Epidermal Growth Factor Receptor Improves Structural, Locomotor, Sensory, and Bladder Recovery from Experimental Spinal Cord Injury

“…Initiation of hindlimb movement is influenced by 5-HT activation of motor output via a central pattern generator (Rossignol et al, 1998;Grillner and Wallen, 2002) that organizes automated execution of hindlimb movements. Administration of 5-HT or quipazine has been shown to lead to immediate improvement of locomotion (Antri et al, 2005).…”

Cerebellar Contributions to Locomotor Adaptations during Splitbelt Treadmill Walking

“…In many animals, central pattern generators (CPGs) afford the spinal cord nearly autonomous control of basic locomotor rhythms [lamprey (Grillner, 1985;Grillner et al, 1995); frog (Arshavsky et al, 1993;Roberts et al, 1995); turtle (Lennard and Stein, 1977); cat (Brown, 1911;Grillner and Zangger, 1979;Rossignol et al, 1998)]. In humans and other primates, the behavioral and neurophysiological evidence for CPGs remains incomplete, although studies of humans with spinal cord injury (Calancie et al, 1994;Dimitrijevic et al, 1998) and infant stepping patterns (Yang et al, 1998(Yang et al, , 2004 support the existence of similar circuitry.…”

Ontogeny of Modulatory Inputs to Motor Networks: Early Established Projection and Progressive Neurotransmitter Acquisition

“…In vertebrates, adult CPGs can produce multiple motor outputs under the control of different modulatory signals (Sillar et al, 1997;Rossignol et al, 1998;Lieske et al, 2000). These CPGs are present very early in development (Sillar et al, 1997;Fenelon et al, 1998b;Kudo and Nishimaru, 1998;Branchereau et al, 2001) and also express multiple outputs in response to distinct modulatory environments (Sillar et al, 1998;Branchereau et al, 2001).…”