, 2011) (Figure 3C). Dorsal extensor premotor interneurons receive a high density of synaptic input by proprioceptive sensory neurons in contrast to the more laterally located flexor premotor interneurons (Tripodi et al., 2011) (Figure 3C). These findings provide anatomical evidence for the electrophysiologically well-studied disynaptic pathway from proprioceptors to extensor motor neurons (Angel et al., 2005, Conway et al., 1987,

McCrea, 1998 and Pearson et al., 1998) and offer another example of a correlative link between the spatial distribution and synaptic connectivity and/or function of spinal populations. AZD6738 ic50 An additional important factor for the acquisition of neuronal identity is the choice of DAPT purchase neurotransmitter expressed by a given neuronal population. The majority of spinal interneurons signal through either the excitatory neurotransmitter glutamate or the inhibitory neurotransmitter(s)

GABA and/or glycine. Neurotransmitter identity is tightly linked to neuronal subpopulation fate. The transcriptional specification of neuronal subpopulations in the dorsal spinal cord provides an impressive illustration of this fact since transcriptional fate is tightly linked to neurotransmitter choice (Glasgow et al., 2005 and Mizuguchi et al., 2006). Acquisition of inhibitory fate in the dorsal spinal cord is in large part dictated by the transcription factor Ptf1a, and Ptf1a mutant mice exhibit a complete absence of dorsal spinal inhibition ( Glasgow et al., 2005). The balance between excitation and inhibition mediated Calpain by a variety of different interneuron populations controls many of the functional properties and parameters

of motor output bursting behavior. Several recent approaches using mouse genetics provide evidence that interfering with excitatory and inhibitory connectivity can have profound effects on motor behavior. One of the most striking behavioral consequences was reported for mice with mutations in components of the EphrinB3-EphA4 signaling pathway, including the downstream Rac-GAP effector molecule alpha2-Chimerin (Beg et al., 2007, Iwasato et al., 2007, Kullander et al., 2003 and Wegmeyer et al., 2007) (Figure 4A). Mutations in any of these signaling molecules lead to aberrant axonal midline crossing by yet-to-be-identified spinal interneuron subpopulations (Beg et al., 2007, Iwasato et al., 2007, Kullander et al., 2003, Restrepo et al., 2011 and Wegmeyer et al., 2007). This conversion from normally ipsilaterally projecting to “pseudocommissural” interneurons (Figure 4A) is a likely reason for the hopping gait that deviates from the rodent-typical alternating gait. Future work will determine the precise circuit mechanism(s) at the level of neuronal subpopulations responsible for this species-aberrant behavior.