Renshaw cell responses to intra-arterial injection of muscle metabolites into cat calf muscles.

Metabolites released during fatiguing muscle contractions excite group III IV muscle afferents which might inhibit skeleto-motoneuron firing, hypothetically via Renshaw cells. This was tested, in decerebrated, spinalized cats, by recording changes in Renshaw cell spontaneous discharges and responses to antidromic electrical stimulation of motor axons when small-diameter calf muscle afferents were excited by intra-arterially injected bradykinin, serotonin, lactic acid and KCI. Whenever such injections had an effect, it transiently raised or lowered the spontaneous firing rate and almost always decreased the antidromic response to motor axon stimulation. Injection of bradykinin and serotonin commonly decreased the blood pressure and concomitantly the spinal blood flow (as measured using laser Doppler flowmetry), which could have indirectly influenced Renshaw cell firing. But in general, blood pressure and flow changed after the Renshaw cell discharge did, which thus, appears to be modulated independently by group III-IV afferents. These results suggest that the Renshaw cell-mediated effects of neurochemically excited afferents would predominantly disinhibit rather than inhibit motoneurons.

Effects of neurochemically excited group III-IV muscle afferents on motoneuron afterhyperpolarization.

When humans voluntarily and maximally contract a muscle under isometric conditions, the average firing rate of motor units decreases from an initially high value over several tens of seconds. The mechanisms underlying the rate reduction are probably manifold. One mechanism could involve changes in the motoneuron afterhyperpolarization, another reflex effects of group III-IV muscle afferents that are excited during developing muscle fatigue. It appears possible that changes in motoneuron afterhyperpolarization are mediated by these afferent inputs. We therefore studied effects on motoneuron afterhyperpolarization of small-diameter muscle afferents excited by intra-arterially injected metabolites such as bradykinin and serotonin. In decerebrate and mostly spinalized cats, lumbosacral alpha-motoneurons were recorded intracellularly. Current pulses were injected to test for input resistance and elicit action potentials and afterhyperpolarizations. Afterhyperpolarizations were averaged from c. 10 successive stimulus repetitions. Measurements were taken of afterhyperpolarization amplitude, half-width and area; and exponential functions were fitted to the afterhyperpolarization decay phase to determine afterhyperpolarization decay time-constants. In selected cases, the entire afterhyperpolarization trajectory was fitted with a sum of two exponentials to assess more precisely changes in afterhyperpolarization trajectory. Small catheters were inserted into side-branches of the sural artery and the accompanying vein to apply substances like bradykinin, serotonin and KCl to the calf muscles. Concentrations were in the range of those used by other workers. Intra-arterial injection of bradykinin and serotonin usually decreased blood pressure, which may at times have affected mean motoneuron membrane potentials. Afterhyperpolarization amplitude usually changed with membrane potential in a way expected from ensuing changes in driving potential. Whenever excitation of group III-IV muscle afferents caused moderate to strong increases in motoneuron synaptic noise, afterhyperpolarization amplitudes were reduced, usually in parallel to decreases in input resistance. Afterhyperpolarization half-widths were mostly unaffected, but occasionally decreased. There was a significant trend for afterhyperpolarization decay time-constants to increase during increased synaptic noise, this increase being inversely correlated with the reduction in afterhyperpolarization amplitude. The reduction in input resistance was associated with a decrease in the membrane time-constant, which could therefore not account for the prolongation of the afterhyperpolarization decay time-constant. The afterhyperpolarization area decreased, indicating that the reduction of afterhyperpolarization amplitude outweighed the prolongation of afterhyperpolarization decay time-constant. During a prolonged fatiguing muscle contraction group III-IV afferents become increasingly excited, produce augmenting synaptic inputs in motoneurons, and will change afterhyperpolarization properties. On average, these changes per se tend to diminish the effect of afterhyperpolarization on motoneuron discharge.

Renshaw cells and recurrent inhibition: comparison of responses to cyclic inputs.

Spinal recurrent inhibition influences the discharge patterns of motoneurons and spinal interneurons. The precise pattern of this influence depends on the static and dynamic characteristics of this feedback system. It is thus of importance to quantify its characteristics as well as possible. We here compare nonlinear features (hysteresis) in Renshaw cells and recurrent inhibition in response to cyclic stimulation of motor axons. In pentobarbitone-anaesthetized or decerebrate cats, intracellular recordings were obtained from 26 hindlimb muscle nerves skeleto-motoneurons and extracellular recordings from nine Renshaw cells. Various hindlimb muscle nerves (dorsal roots cut) or ventral roots (dorsal roots intact) were prepared for electrical stimulation to elicit recurrent inhibition in motoneurons or discharges in Renshaw cells. Stimulus patterns consisted of repetitive pulse trains whose rates varied cyclically between around 10 pulses/s and several tens of pulses/s, at modulation frequencies between 0.1 and 1.0 Hz, in one of two waveforms: triangular or sinusoidal. Recurrent inhibitory potentials in motoneurons and discharge patterns of Renshaw cells were averaged with respect to triggers (cycle-triggers) marking a fixed phase in the stimulation cycle. In another two experiments, motor axons to hindlimb muscles (soleus and medial gastrocnemius) were stimulated with sinusoidal and distorted temporal patterns to show their effects on force production. Most often the cycle-averaged motoneuron membrane potential changed in a temporally asymmetrical way, i.e. it fairly rapidly hyperpolarized early in the stimulus cycle (during increasing rate) and then depolarized more slowly throughout the rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Waveform parameters of recurrent inhibitory postsynaptic potentials in cat motoneurons during time-varying activation patterns.

A considerable number of theoretical and experimental studies have been undertaken to establish quantitative relationships between the time course of postsynaptic potentials in a neuron and the change in firing probability thereby induced. Depending on background synaptic noise level, the time course of the postsynaptic potential per se as well as its time derivative are both of importance in varying proportion. We have recently begun to study recurrent inhibitory potentials in cat hindlimb motoneurons during rhythmically varying rates of stimulation of motor axons. The amplitude-rate relationship exhibits hysteresis in that amplitudes are usually larger during augmenting than decrementing rates in the cycle. We here report results on the other important variable, that is the slope of recurrent inhibitory potential development, which need not a priori be correlated with amplitude. We found that the slope has a relation to stimulus rate similar to amplitude, so that both parameters are correlated. In pentobarbitone anaesthetized or decerebrate cats, intracellular recordings were obtained from hindlimb skeleto-motoneurons. Various hindlimb muscle nerves were prepared for electrical stimulation to elicit recurrent inhibitory potentials, with dorsal roots cut. Test stimulus patterns consisted of repetitive pulse trains whose rates varied, at modulation frequencies between 0.1 and 1.0 Hz, in one of two waveforms: triangular or sinusoidal. Modulation depths were either "full", with rates varying between a minimum of less than 10 and a maximum of around 50 pulses per s. Or they were about "half" this depth, with mean rates shifted into a "low", "medium" or "high" rate region. Recurrent inhibitory potentials were averaged with respect to stimuli occurring during different phases of the stimulation cycle. Most often when, throughout the cycle, the amplitude changed in a consistent way, so did the slopes of the inhibitory potentials. That is, when the amplitudes rhythmically declined with increasing and recovered with decreasing stimulus rate, the rate of hyperpolarization followed the same pattern. With prominent hysteresis in amplitude, a corresponding hysteresis appeared in slopes. Hence, amplitude and slopes were correlated, occasionally showing a hysteresis among themselves. To a certain extent, these results can be explained by Renshaw cell behaviour, the contribution of the Renshaw cell-motoneuron synapse being unknown and difficult to assess experimentally. For the inhibitory effect of Renshaw cells on motoneurons (and reciprocal Ia inhibitory interneurons), both its magnitude and its time course probably play an important role in determining the efficacy of counteracting local excitatory inputs. The change in slope of inhibitory potentials, and likely its underlying conductance, during cyclic motoneuron activation can be presumed to significantly contribute to the temporal pattern of discharge of motoneurons, in particular in relation to the prevention of synchronization leading to enhanced tremor.