Plateau Potentials in Sacrocaudal Motoneurons of Chronic Spinal Rats, Recorded In Vitro

Abstract

Intracellular recordings were made from sacrocaudal tail motoneurons of acute and chronic spinal rats to examine whether plateau potentials contribute to spasticity associated with chronic injury. The spinal cord was transected at the S2 level, causing, over time, exaggerated long-lasting reflexes (hyperreflexia) associated with a general spasticity syndrome in the tail muscles of chronic spinal rats (1-5 mo postinjury). The whole sacrocaudal spinal cord of chronic or acute spinal rats was removed and maintained in vitro in normal artificial cerebral spinal fluid (ACSF). Hyperreflexia in chronic spinal rats was verified by recording the long-lasting ventral root responses to dorsal root stimulation in vitro. The intrinsic properties of sacrocaudal motoneurons were studied using intracellular injections of slow triangular current ramps or graded current pulses. In chronic spinal rats, the current injection triggered sustained firing and an associated sustained depolarization (plateau potential; 34/35 cells; mean, 5.5 mV; duration >5 s; normal ACSF). The threshold for plateau initiation was low and usually corresponded to an acceleration in the membrane potential just before recruitment. After recruitment and plateau activation, the firing rate changed linearly with current during the slow ramps [63% of cells had a linear frequency-current (F-I) relation] despite the presence of the plateau. The persistent inward current (I(PIC)) producing the plateau and sustained firing was estimated to be on average 0.8 nA as determined by the reduction in injected current needed to stop the sustained firing [DeltaI = -0.8 +/- 0.6 (SD) nA], compared with the current needed to start firing (I = 1.7 +/- 1.5 nA; 47% reduction). In motoneurons of acute spinal rats, plateaus were rarely seen (3/22), although they could be made to occur with bath application of serotonin. In motoneurons of chronic spinal rats there were no significant changes in the mean passive input resistance, rheobase or amplitude of the spike afterhyperpolarization (AHP) as compared with acute spinal rats. However, there were significant increases in AHP duration and initial firing rate at recruitment and decreases in minimum firing rate and F-I slope. We suggest that the higher initial firing rate resulted from the plateau activation at recruitment and the lower F-I slope resulted from an increase in active conductance during firing, due to I(PIC). Brief dorsal root stimulation also triggered a plateau and sustained discharge (long-lasting reflexes; 2-5 s) in motoneurons of chronic (but not acute) spinal rats. When the plateau was eliminated by a hyperpolarizing current bias, the reflex response was significantly shortened (to 1 s). Thus plateaus contributed substantially to the long-lasting reflexes in vitro and therefore should contribute significantly to the corresponding exaggerated reflexes and spasticity in awake chronic spinal rats.

Beginning at the end: Repetitive firing properties in the final common pathway

“…In the acutely transected spinal cord, PICs are not present in either cat lumbar motoneurons (Hounsgaard et al, 1988) or rat sacral motoneurons (Bennett et al, 2001). Following chronic injury, however, Bennett et al (2001) showed that PICs are readily expressed. They attributed this, at least in part, to a developed hypersensitivity of motoneurons to serotonin.…”

Spasticity after spinal cord injury

“…Recent animal research suggested that a recovery of relatively normal motor neuron excitability and plateau potential behavior (sustained depolarizations), in the absence of normal inhibitory control to turn off plateaus and associated sustained firing, may be implicated in the recovery of spinal shock following SCI. 32 Intrinsic tonic spasticity Decq 2 has differentiated intrinsic tonic spasticity (increased muscle tone) as that component of spasticity resulting from an exaggeration of the tonic component of the stretch reflex. Briefly, the stretch reflex is a monosynaptic reflex pathway that originates in the muscle spindles embedded parallel to the muscle fibers and travels via a Ia afferent to the spinal cord, where it synapses either first with interneurons or directly with an alpha motor neuron innervating the muscle from which the stimulus originated.…”

Spinal shock revisited: a four-phase model

“…19,20 5-HT and NE act on spinal motor neurons yielding plateau potentials, which may amplify excitatory inputs including reflex inputs. [21][22][23] Plateau potentials originate on dendrites and amplify excitatory inputs up to six-fold, thus leading to sustained firing with minimal excitatory input. 24 This effect may be due to prolonged activation of Ca 2 þ channels.…”

“…108 Spinal motoneurons below a transection show lowthreshold, prolonged, self-sustained motor-unit firing (minutes to hours) in association with hyper-reflexia; this hyperexcitable motoneuron behavior is present by 30 days after cord transection in rats but not at 2 days. 23,108 The late appearance of plateau potentials below SCI is proposed as a factor in late developing hyper-reflexia. Plateau potentials may result from synthesis of new ionic channels yielding recruitment of new voltage-activated calcium conductance.…”