Serotonin Modulates the Properties of Ascending Commissural Interneurons in the Neonatal Mouse Spinal Cord

Abstract

The interneuron populations that constitute the central pattern generator (CPG) for locomotion in the mammalian spinal cord are not well understood. We studied the properties of a set of commissural interneurons whose axons cross and ascend in the contralateral cord (aCINs) in the neonatal mouse. During N-methyl-D-aspartate (NMDA) and 5-HT-induced fictive locomotion, a majority of lumbar (L2) aCINs examined were rhythmically active; most of them fired in phase with the ipsilateral motoneuron pool, but some fired in phase with contralateral motoneurons. 5-HT plays a critical role in enabling the locomotor CPG to function. We found that 5-HT increased the excitability of aCINs by depolarizing the membrane potential, reducing the postspike afterhyperpolarization amplitude, broadening the action potential, and decreasing the action potential threshold. Serotonin had no significant effect on the input resistance and sag amplitude of aCINs. These results support the hypothesis that aCINs play important roles in coordinating left-right movements during fictive locomotion and thus may be component neurons in the locomotor CPG in neonatal mice.

Intrinsic and Functional Differences among Commissural Interneurons during Fictive Locomotion and Serotonergic Modulation in the Neonatal Mouse

“…4 A). In two cells, serotonin additionally evoked small (3.4 Ϯ 0.4 mV) membrane oscillations that resembled truncated action potentials; these were seen more often in our previous study of aCINs, in which they were shown to arise from electrical coupling to unknown spiking neurons (Zhong et al, 2006). The depolarizing effect of 5-HT peaked at or shortly after the end of 5-HT application (Fig.…”

“…Furthermore, 5-HT de-polarizes and increases the excitability of dCINs but has no effect on adCINs. In a previous study (Zhong et al, 2006), we showed that aCINs also fire rhythmically during fictive locomotion and are excited by 5-HT. Our results suggest that these anatomically distinct CINs can be functionally differentiated: dCINs and aCINs, but not adCINs, are potential components of the spinal locomotor network of the neonatal mouse.…”

“…Commissural interneurons were identified by a collision test (Fig. 1C), in which orthodromic action potentials evoked by current injection in the soma collided with and eliminated appropriately timed antidromic action potentials evoked by stimulation of the contralateral hemicord (Zhong et al, 2006). Cells were accepted as CINs if they passed a collision test with hemicord stimulation with glutamatergic, GABAergic, and glycinergic fast synaptic transmission blocked.…”

“…A cycle of motor nerve activity started at the onset of a contralateral L2 (cL2) ventral root burst and ended at the onset of the next cL2 burst; these onsets were determined by a custom-made program in Spike2 to detect when the rectified signal exceeded the average noise level between bursts by a preset amount. A double normalization process was used in this study to analyze the phasing of neural activity during the locomotor cycle (Shefchyk and Jordan, 1985;Berkowitz and Stein, 1994;Zhong et al, 2006). The period of cL2 activity was divided into the first five equal time bins, whereas the rest of the cycle (monitored with iL2 Figure 1.…”

“…The action potential properties and other membrane properties of dCINs and adCINs are compared in Table 1. To allow full comparison, we also include in this table the corresponding data for aCINs (Zhong et al, 2006). Collectively, there were no significant differences between dCINs, aCINs, and adCINs for any of the parameters we measured.…”