depolarization of motoneurons in vivo by the 5-HT 2 agonist DOI and its effect on synaptic noise. Lee, R.H., J.F. Miller, W.Z. Rymer and C.J. Heckman. Department of Physiology, Northwestern University School of Medicine, Chicago, IL 60611.
APStracts 2:0290N, 1995.
SUMMARY AND CONCLUSIONS
1. The enhanced excitability of extensor motoneuron pools generated by the 5- HT 2 agonist DOI was investigated using intracellular recording from medial gastrocnemius (MG) and lateral gastrocnemius-soleus (LGS) motoneurons in the spinalized decerebrate preparation. Our primary hypothesis was that DOI actions were not just due to direct depolarization of motoneurons but also involved activation of a synaptic input system. 2. Because DOI increased blood pressure, before and after DOI measurements within single cells were only achieved in a small sample (n = 5). DOI strongly depolarized all 5 cells (mean: 13 mV; range: 10-16 mV) while at the same time sharply increasing membrane noise. The DOI-induced depolarization reduced the rheobases of 3 cells with control values of > 20 nA by 13 to 18 nA. Input resistance measurements in 3 cells revealed small increases (4% in 2 cells, 27% in the third cell). 3). An extensive analysis of the effect of DOI was carried out by comparing two separate cell samples, one control (n = 52) and one following DOI administration (n = 56). Several intrinsic motoneuron properties were not statistically different in the two samples: input resistance, afterhyperpolarization (AHP) amplitude, and conduction velocity. However, the average rheobase in the post-DOI sample (7.8+/-7.1 nA) was significantly lower than in the control sample (13.0+/-8.0 nA). Moreover, in 10 of the 56 cells in the post-drug sample, rheobases were actually negative, that is, the cells exhibited persistent rhythmic firing. 4). The reduction in rheobase did not alter the slope of the regression relations between it and the other intrinsic properties (input resistance, AHP amplitude, and conduction velocity). Given the known correlations between motoneuron electrical properties and the mechanical properties of the muscle fiber it innervates, this means that DOI had approximately equal effects on motoneurons innervating slow twitch (S) and fast twitch (F) muscle fibers. 5). The amplitude of the membrane noise in the post-drug sample was approximately twice as large as in the control sample. Large spontaneous depolarizations of up to 10 mV were sometimes seen, but both the noise and the large depolarizations were highly irregular and did not resemble locomotor drive potentials. 6). Rhythmic firing in response to injected current steps was extremely variable. Accelerations and pauses were frequent and the average discharge rate to a constant amplitude step could vary by a factor of 2. Firing sometimes persisted after the end of the current step and some of these afterdischarges appeared to have been due to plateau potentials, but this impression could not be verified because of the frequent presence of spontaneous but irregular depolarizations. 7). Comparisons of the fluctuations in membrane potential in single cells and variations in the electroneurograms (ENG) of the MG and LGS nerves showed that single cell noise and population discharge patterns closely covaried when DOI was present. In control conditions, application of steady stretch produced cell-ENG correlations (r 2 mean+/-standard deviation: 0.16+/-0.03 in 10 cells) that were much smaller than those generated by DOI (0.54+/-0.05 in 6 cells). 8) These findings indicate the DOI activated a previously quiescent set of spinal interneurons. The identity of these interneurons is as yet unknown, but it is clear the input they generate is highly irregular but yet highly correlated across many motoneurons simultaneously. The presence of this input made it difficult to assess what proportion of the DOI depolarization was due to changes in intrinsic motoneuron voltage sensitive channels vs. increases in synaptic current. The relevance of the uniform effect of DOI on S vs. F motoneurons for enhancement of gain of the system input-output function for the entire motoneuron pool is discussed. 

Received 17 March 1995; accepted in final form 14 September 1995.
APS Manuscript Number J178-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95