Active Dendritic Integration of Inhibitory Synaptic Inputs in Vivo

Synaptic integration in vivo often involves activation of many afferent inputs whose firing patterns modulate over time. In spinal motoneurons, sustained excitatory inputs undergo enormous enhancement due to persistent inward currents (PICs) that are generated primarily in the dendrites and are dependent on monoaminergic neuromodulatory input from the brain stem to the spinal cord. We measured the interaction between dendritic PICs and inhibition generated by tonic electrical stimulation of nerves to antagonist muscles during voltage clamp in motoneurons in the lumbar spinal cord of the cat. Separate samples of cells were obtained for two different states of monoaminergic input: standard (provided by the decerebrate preparation, which has tonic activity in monoaminergic axons) and minimal (the chloralose anesthetized preparation, which lacks tonic monoaminergic input). In the standard state, steady inhibition that increased the input conductance of the motoneurons by an average of 38% reduced the PIC by 69%. The range of this reduction, from <10% to >100%, was proportional to the magnitude of the applied inhibition. Thus nearly linear integration of synaptic inhibition may occur in these highly active dendrites. In the minimal state, PICs were much smaller, being approximately equal to inhibition-suppressed PICs in the standard state. Inhibition did not further reduce these already small PICs. Overall, these results demonstrate that inhibition from local spinal circuits can oppose the facilitation of dendritic PICs by descending monoaminergic inputs. As a result, local inhibition may also suppress active dendritic integration of excitatory inputs.