Active Dendritic Integration of Inhibitory Synaptic Inputs In Vivo

Abstract

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.

Serotonin Affects Movement Gain Control in the Spinal Cord

“…This unspecific control can be negated by reciprocal inhibition mediated by spindle Ia afferents and Ia interneurons (Hyngstrom et al, 2007;Bui et al, 2008). Dendritic persistent inward current, which is the main mechanism of serotonergic control of motoneuron gain, is highly sensitive to this inhibition (Hultborn et al, 2003;Kuo et al, 2003). Thus, the nervous system can still offer specific control with a diffusive neuromodulation background if the descending motor commands are coupled to both brainstem monoaminergic nuclei and to reciprocal inhibitory interneurons in the spinal cord (Heckman et al, 2008).…”

Disturbances of motor unit rate modulation are prevalent in muscles of spastic-paretic stroke survivors

“…Thus far, only the interactions between the PIC and sources of excitatory synaptic input have been considered. The PIC, however, is also known to be highly sensitive to inhibitory synaptic input (Bui et al 2008a(Bui et al , 2008bHounsgaard et al 1988;Kuo et al 2003). In fact, Powers et al (2012) suggested that the contribution of PICs to rate modulation is likely to depend on a mixture of excitatory and inhibitory synaptic currents contributing to the net synaptic drive to the motoneuron pool.…”

Staircase Currents in Motoneurons: Insight into the Spatial Arrangement of Calcium Channels in the Dendritic Tree

“…However, voltage-activated calcium currents in motoneuron dendrites, which generate "persistent inward currents" (PICs), appear to ensure integration of even distal inputs Li and Bennett, 2003). PICs generate plateau potentials (Hounsgaard and Kiehn, 1989;Lee and Heckman, 1996) and amplify synaptic inputs to motoneurons, both excitatory (Brownstone et al, 1994;Bennett et al, 1998;Lee and Heckman, 2000;Jones and Lee, 2006;Powers et al, 2008) and inhibitory (Hultborn et al, 2003;Kuo et al, 2003;Bui et al, 2008a).…”