Enhancement of Bistability in Spinal Motoneurons In Vivo by the Noradrenergic α₁ Agonist Methoxamine

Abstract

Enhancement of bistability in spinal motoneurons in vivo by the noradrenergic alpha1 agonist methoxamine. Like many types of motoneurons, spinal motoneurons in the adult mammal can exhibit bistable behavior. This means that short periods of excitatory input can initiate long periods of self-sustained firing and that equally short periods of inhibition can return the cell to the quiescent state. Usually, the presence of one of the monoamines (either serotonin or norepinephrine) is required for spinal motoneurons to express bistable behaviors. Because the decerebrate cat preparation has tonic activity in monoaminergic fibers that originate in the brain stem and project to spinal motoneurons, these cells sometimes exhibit bistable behavior. However, exogenous application of the noradrenergic alpha1 agonist methoxamine greatly enhances bistable behavior in the decerebrate. The goal of this study was to identify the mechanisms of this action of methoxamine. The total persistent inward current (IPIC) in spinal motoneurons in the decerebrate cat was measured from I-V functions generated by triangular voltage commands applied using discontinuous single electrode voltage clamp. The effect of methoxamine on IPIC was assessed by comparing its properties in a control cell sample without methoxamine to its properties in a sample of cells obtained after application of methoxamine. In most experiments, at least one cell was obtained from each sample. Our results showed that methoxamine approximately doubled the amplitude of IPIC without changing its onset voltage, its offset voltage, or its persistence. The reduced amplitude was a consistent finding within experiments and so was unlikely to be caused by interanimal variability. In addition, methoxamine depolarized motoneurons without altering their input conductances, so that a smaller amount of current was required to reach the onset voltage of IPIC. These effects of methoxamine were approximately equal in all cells. As a result of these changes, methoxamine greatly enhanced the tendency for motoneurons to become bistable. It is proposed that the methoxamine-induced increase in the amplitude of IPIC is effective in enhancing the duration of bistable firing because this increase makes IPIC more resistant to the deactivating effects of the afterhyperpolarizations between spikes.

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

“…Much of the work to date has focused on monoaminergic regulation of motoneuron properties. Specifically, serotonin and noradrenaline have been studied and shown to modulate PICs (Section 6; see also Lee and Heckman, 1999;Heckman et al, 2003) and voltage threshold (Fedirchuk and Dai, 2004).…”

Spastic Long-Lasting Reflexes in the Awake Rat After Sacral Spinal Cord Injury

“…Prior to spinal cord injury, PICs are present and prominently amplify normal motoneuron output (Hounsgaard et al 1988;Lee and Heckman 1999); however, low-threshold long EPSPs do not appear to be prominent, and there is strong descending and segmental inhibitory control that can terminate motoneuron firing, even though it is maintained by intrinsic PICs (Fig. 7, long inhibitory reflex).…”

“…Acutely, hours or days after the injury, the spinal cord is nonexcitable. This lack of excitability is predictable from a number of studies of the intrinsic electrical properties of motoneurons, which have shown that motoneuron excitability is dependent on inputs descending from the brain stem and releasing the neuromodulators serotonin and norepinephrine, and this is lost after injury (Conway et al 1988;Hounsgaard et al 1988;Lee and Heckman 1999). Such neuromodulators allow the motoneuron to exhibit sustained depolarizations known as plateau potentials, which are due to slowly activating voltage-dependent persistent inward currents (PICs), in large part mediated by the low-voltage-activated Cav1.3 L-type calcium channels in the dendrites (Hounsgaard and Kiehn 1989;Perrier and Hounsgaard 2003;Powers and Binder 2001).…”

Motor Neuron Firing Dysfunction in Spastic Patients With Primary Lateral Sclerosis

“…The stable firing rates of motor neurons of PLS patients would be compatible with activation of a plateau potential, albeit at an abnormally low membrane potential. Low-voltage plateau potentials could occur if channels were activated at an extremely low voltage, even below threshold for firing, as could theoretically occur under conditions of high monoaminergic tone (Hounsgaard and Kiehn 1989;Lee and Heckman 1999) or if the numbers of channels were reduced. In animal models of chronic spinal injury, the voltage threshold for persistent inward currents was found to be less than the firing threshold for the motor neuron (Li and Bennett 2003;Li et al 2004).…”