Interactions between focused synaptic inputs and diffuse neuromodulation in the spinal cord.

Spinal motoneurons (MNs) amplify synaptic inputs by producing strong dendritic persistent inward currents (PICs), which allow the MN to generate the firing rates and forces necessary for normal behaviors. However, PICs prolong MN depolarization after the initial excitation is removed, tend to "wind-up" with repeated activation and are regulated by a diffuse neuromodulatory system that affects all motor pools. We have shown that PICs are very sensitive to reciprocal inhibition from Ia afferents of antagonist muscles and as a result PIC amplification is related to limb configuration. Because reciprocal inhibition is tightly focused, shared only between strict anatomical antagonists, this system opposes the diffuse effects of the descending neuromodulation that facilitates PICs. Because inhibition appears necessary for PIC control, we hypothesize that Ia inhibition interacts with Ia excitation in a "push-pull" fashion, in which a baseline of simultaneous excitation and inhibition allows depolarization to occur via both excitation and disinhibition (and vice versa for hyperpolarization). Push-pull control appears to mitigate the undesirable affects associated with the PIC while still taking full advantage of PIC amplification.