Systematic Shifts in the Balance of Excitation and Inhibition Coordinate the Activity of Axial Motor Pools at Different Speeds of Locomotion

Abstract

An emerging consensus from studies of axial and limb networks is that different premotor populations are required for different speeds of locomotion. An important but unresolved issue is why this occurs. Here, we perform voltage-clamp recordings from axial motoneurons in larval zebrafish during "fictive" swimming to test the idea that systematic differences in the biophysical properties of axial motoneurons are associated with differential tuning in the weight and timing of synaptic drive, which would help explain premotor population shifts. We find that increases in swimming speed are accompanied by increases in excitation preferentially to lower input resistance (Rin) motoneurons, whereas inhibition uniformly increases with speed to all motoneurons regardless of Rin. Additionally, while the timing of rhythmic excitatory drive sharpens within the pool as speed increases, there are shifts in the dominant source of inhibition related to Rin. At slow speeds, anti-phase inhibition is larger throughout the pool. However, as swimming speeds up, inhibition arriving in-phase with local motor activity increases, particularly in higher Rin motoneurons. Thus, in addition to systematic differences in the weight and timing of excitation related to Rin and speed, there are also speed-dependent shifts in the balance of different sources of inhibition, which is most obvious in more excitable motor pools. We conclude that synaptic drive is differentially tuned to the biophysical properties of motoneurons and argue that differences in premotor circuits exist to simplify the coordination of activity within spinal motor pools during changes in locomotor speed.

Peeling back the layers of locomotor control in the spinal cord

“…2A). A recent study using voltage-clamp recordings in larval zebrafish has begun to elucidate the synaptic basis for synchronizing activity among heterogeneous motor neurons during rhythmic locomotion [19]. In particular, increases in the frequency of fictive swimming are associated with a preferential increase in excitatory drive to less excitable motor neurons (Fig.…”

“…A recent anatomical study in larvae has demonstrated that more dorsal V2a neurons have the potential to make systematically more connections to less-excitable motor neurons by virtue of convergent intersegmental axonal projections [24]. This could provide the observed bias in rhythmic excitation during faster swimming [19]. In juvenile/adult zebrafish young enough to use Chx10 expression to identify V2a neurons [25], the spatial recruitment pattern is obscured by neuronal migration, but there are still differences in V2a activation patterns from low to medium frequencies of swimming evoked by bulk electrical stimulation [26].…”

“…Critically, both models predict the same maximal distribution of excitatory drive across the motor pool at the fastest speeds. A new model (bottom) based on [19] has maximal drive (grey arrows) weighted to neuronal excitability across the motor pool. (b) In larval and juvenile zebrafish, V2a neurons comprise the UBG and provide appropriately biased drive to the motor pool [24,27].…”

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

“…by blocking inhibition (Dichter and Ayala, 1987; Bazhenov et al, 2008). The concept of balanced excitation (E) and inhibition (I) (balanced networks in short) was introduced two decades ago (Shadlen and Newsome, 1994; van Vreeswijk and Sompolinsky, 1996) and has sparked numerous studies both theoretical (Amit and Brunel, 1997; Ozeki et al, 2009; van Vreeswijk and Sompolinsky, 1998; Kumar et al, 2008) as well as experimental (Berg et al, 2007; Okun and Lampl, 2008; Higley and Contreras, 2006; Wehr and Zador, 2003; Kishore et al, 2014). The primary purpose of theoretical models of balanced networks was initially to understand irregular spiking, which was widely observed in experiments (Bell et al, 1995; Shadlen and Newsome, 1994).…”

A Gradient in Synaptic Strength and Plasticity among Motoneurons Provides a Peripheral Mechanism for Locomotor Control

“…Within the axial motoneuron pool in the zebrafish spinal cord, early born, large primary motoneurons (PMns) have lower input resistance (Rin) and require larger currents to be recruited; later born, smaller secondary motoneurons (SMns) have higher Rin and can be activated by smaller input currents [5–10]. Anatomical studies have shown that PMns and SMns have various axonal projection patterns to skeletal muscles [8, 11].…”