Premotor Spinal Network with Balanced Excitation and Inhibition during Motor Patterns Has High Resilience to Structural Division

Abstract

Direct measurements of synaptic inhibition (I) and excitation (E) to spinal motoneurons can provide an important insight into the organization of premotor networks. Such measurements of flexor motoneurons participating in motor patterns in turtles have recently demonstrated strong concurrent E and I as well as stochastic membrane potentials and irregular spiking in the adult turtle spinal cord. These findings represent a departure from the widespread acceptance of feedforward reciprocal rate models for spinal motor function. The apparent discrepancy has been reviewed as an experimental artifact caused by the distortion of local networks in the transected turtle spinal cord. We tested this assumption in the current study by performing experiments to assess the integrity of motor functions in the intact spinal cord and the cord transected at segments D9/D10. Excitatory and inhibitory synaptic inputs to motoneurons were estimated during rhythmic motor activity and demonstrated primarily intense inputs that consisted of qualitatively similar mixed E/I before and after the transection. To understand this high functional resilience, we used mathematical modeling of networks with recurrent connectivity that could potentially explain the balanced E/I. Both experimental and modeling data support the concept of a locally balanced premotor network consisting of recurrent E/I connectivity, in addition to the well known reciprocal network activity. The multifaceted synaptic connections provide spinal networks with a remarkable ability to remain functional after structural divisions.

Lognormal firing rate distribution reveals prominent fluctuation–driven regime in spinal motor networks

“…The array recordings were performed simultaneously with recording of the intracellular activity of a single neuron in parallel with electroneurograms (ENGs) from relevant motor nerves (Figure 2D). Site–specific rhythmic hindlimb scratching was induced by tactile touch of the carapace (Berkowitz et al, 2010; Stein, 2005) and could be reproduced reliably over multiple trials (Petersen et al, 2014; Vestergaard and Berg, 2015). The extracellular multielectrode arrays, which were used, were custom–designed for the spinal cord (Berg64-probe, Neuronexus inc.) to enable efficient polytrode spike sorting (Figure 2E and Figure 2—figure supplement 2).…”

“…This view was essentially predicted much earlier in random walk models (Gerstein and Mandelbrot, 1964). The concept of balanced E/I is now an integrated part of understanding network processing in cortex and elsewhere, but for some reason it has been forgotten in understanding spinal motor networks, with the exception of a few isolated studies (Berg et al, 2007; Petersen et al, 2014). …”

Inhibition downunder: an update from the spinal cord

“…Three recent papers have highlighted the potential contribution that inhibition makes to balanced motor neuron excitability. Berg and his co-authors [49,50], in examining inhibitory and excitatory currents in motor neurons during bouts of fictive scratching, found a parallel increase in excitation and inhibition. This pattern of inputs to motor neurons seems counterintuitive given that flexion-extension movements during scratching involve the production of an alternating pattern of inhibitory and excitatory drive to motor neurons by reciprocal inhibition.…”

“…One possibility is that it changes the gain in motor neurons and thus their dynamic range [51], in much the same way that coupled inhibition-excitation has been proposed regulate the input-output properties of cortical neurons. Berg and colleagues [50] suggest that balanced excitation-inhibition is likely to be important for fine motor control, one example being grip movements. During precision gripping, there is increased phasic and tonic activity in pre-motor interneurons as compared to wrist flexion-extension movements [52].…”

“…The degree of diversity that exists within these broader inhibitory neuron populations has not been determined. The dI4/dIL A population appears to be comprised of multiple populations that are marked by the expression of different neuropeptides and transcription factors [47–50]. This suggests a high degree of complexity in the composition of inhibitory circuits in the spinal cord.…”