Adjustable amplification of synaptic input in the dendrites of spinal motoneurons in vivo

Abstract

The impact of neuromodulators on active dendritic conductances was investigated by the use of intracellular recording techniques in spinal motoneurons in the adult cat. The well known lack of voltage control of dendritic regions during voltage clamp applied at the soma was used to estimate dendritic amplification of a steady monosynaptic input generated by muscle spindle Ia afferents. In preparations deeply anesthetized with pentobarbital, Ia current either decreased with depolarization or underwent a modest increase at membrane potentials above -40 mV. In unanesthetized decerebrate preparations (which have tonic activity in axons originating in the brainstem and releasing serotonin or norepinephrine), active dendritic currents caused strong amplification of Ia input. In the range of -50 to -40 mV, peak Ia current was over four times as large as that in the pentobarbital-anesthetized preparations. Exogenous administration of a noradrenergic agonist in addition to the tonic activity further enhanced amplification (sixfold increase). Amplification was not seen in preparations with spinal transections. Overall, the dendritic amplification with moderate or strong neuromodulatory drive was estimated to be large enough to allow the motoneurons innervating slow muscle fibers to be driven to their maximum force levels by remarkably small synaptic inputs. In these cells, the main role of synaptic input may be to control the activation of a highly excitable dendritic tree. The neuromodulatory control of synaptic amplification provides motor commands with the potential to adjust the level of amplification to suit the demands of different motor tasks.

Fig. 1.

The monosynaptic input from muscle spindle Ia afferents generates prolonged and steady synaptic currents. Vibration was applied for 10 sec while the cell was clamped at −60 mV.

Fig. 2.

Measurement of the effect of active dendritic conductances on Ia synaptic input. The motoneuron illustrated is in the standard neuromodulatory state (see Materials and Methods).A, Top trace, The relationship between current and voltage generated by the use of single-electrode voltage clamp to apply a linearly rising voltage command that was slow enough to approximate steady-state conditions (Lee and Heckman, 1998b). The onset of I_PIC is evident as the start of a negative slope region. Bottom trace, The effect of applying a steady background of synaptic input from muscle spindle Ia afferents throughout the duration of the voltage ramp. Note the shift in onset of I_PIC. B, Subtraction of the current in the bottom trace inA from that in the top trace revealing the effective synaptic current generated at the soma by the Ia input (Ia I_N) as a function of voltage. In a passive neuron, Ia I_N would have declined with voltage. Instead, Ia I_N underwent strong amplification because of dendritic voltage-dependent conductances.

Fig. 3.

Changing neuromodulatory drive changed the amplification of Ia synaptic input. Each panel of the figure shows the changes in Ia I_N as a function of voltage in two cells, one with low input conductance (thick line; Lo Gn) and one with high input conductance (thin line; Hi Gn). See Materials and Methods for techniques used to alter the neuromodulatory state of the cells. A, Amplification is highest in the enhanced neuromodulatory state. B, Amplification in the standard state is shown. C, Amplification is reduced or absent in the minimal state.

Fig. 4.

Peak Ia I_N plotted as a function of input conductance for each cell in each neuromodulatory state (see legend symbols). Only the cells in the control state (Standard) exhibited a statistically significant relation between the two parameters (dashed line; r = 0.75; p < 0.01). There were however large differences in the values of peak IaI_N across the different states.

Fig. 5.

Comparison of peak IaI_N, which occurs at depolarized levels (typically −50 to −40 mV), with the Ia I_Nrecorded at hyperpolarized levels (−65 to −75 mV). Averages and SDs are given for the cells in each of the three neuromodulatory states listed on the x-axis. The hyperpolarized IaI_N reflected the influence of Ia input with reduced activation of voltage-sensitive dendritic conductances. Thus the difference between peak and hyperpolarized points, which increases as neuromodulatory drive increases, gives an estimation of the influence of active dendritic currents. See Results for statistical comparisons.

Fig. 6.

The voltage for peak amplification of Ia synaptic input varied systematically with the input conductance of the motoneuron. In the sample of cells in the standard neuromodulatory state, there was a statistically significant trend for amplification to occur at more depolarized levels in high-input conductance cells (r = 0.71; n = 12;p < 0.05; slope, 8.15; intercept, −55.02). A similar relationship was observed in the sample of cells in the enhanced neuromodulatory state (r = 0.78;n = 14; p < 0.01; slope, 11.54; intercept, −54.59). The difference between the slopes for the standard and enhanced states was not significant (p > 0.05, t tests for slopes).