Organization and connectivity of premotor interneurons in the mouse spinal cord

Movement is the final behavioral output of neuronal activity in the spinal cord. In all
vertebrates, motor neurons are grouped into motor neuron pools, the functional units
innervating individual muscles. Spinal interneurons receive a variety of inputs from the
brain, cerebellum and sensory afferents, process this information and as the final outcome, the information reaches the motor neurons that control the activation of the innervated muscles. For generation of movement, precise activation of distinct motor neuron pools at the right moment in time is crucial and this precision is possible due to the cohorts of spinal interneurons, connected with specificity to distinct motor neuron pools that regulate motor neuronal activity. How premotor circuits connect to distinct motor neuron pools with specificity is poorly understood and represented a main question of my PhD thesis work.
In my thesis, I present the results of my studies on connectivity of premotor
interneuron populations to specific motor neuron pools in two layers - as general
distribution patterns specific to control the regulation of particular muscles and by closer
examination of the connection specificity of one class of the spinal pre-motor interneurons, the cholinergic partition cells. One significant part of this project was to develop a tool that allowed studying the pre-motor interneurons innervating defined motor neuron pools. For this purpose, I have adapted a novel rabies virus based tool (Wickersham et al. (2007b)) for mono- transsynaptic tracing of neuronal circuits in the spinal cord in vivo. I was successful in establishing an anatomical rabies-virus based connectivity assay in early postnatal mice in order to study the connectivity scheme of premotor neurons, the neuronal cohorts monosynaptically connected to motor neurons. The main parts of my thesis focus on:
1) motor neuron pools connectivity with premotor interneurons that appear to
be widely-distributed when analysed at the segmental level, yet group into stereotypic
populations, and differing for pools innervating functionally-distinct muscles;
2) local or segmental distribution of interneurons depending on their molecular identity; 3) specificity of the connectivity of cholinergic partition cells involved in the regulation of motor neuron excitability - this subpopulation of premotor interneurons segregate into ipsilaterally and bilaterally projecting populations, the latter exhibiting preferential connections to equivalent motor neuron pools bilaterally. A minor part of my thesis is devoted to the connectivity of the spinal pre-motor interneurons in α2-chimaerin mutant mice. Data presented in this part are preliminary and this project needs continuation, but the results begin to provide insight into the function of the α2-chimaerin molecule in the axon guidance and perhaps connectivity process of the bilaterally projecting subclass of partition cells and a dorsal subgroup of premotor interneurons. I demonstrate that the distribution of cholinergic partition cells connected to a particular motor neuron pool is different in α2-chimaerin mutant mice than in the wild-type mice. I also show that the distribution pattern of ectopic bilaterally projecting premotor interneurons in α2-chimaerin mutant mice what concerns the dorsal population of premotor interneurons. These studies of premotor interneurons visualize the widespread but precise nature of connectivity with motor neuron pools, reveal exquisite synaptic specificity for bilaterally projecting cholinergic partition cells and show the importance of the α2-chimaerin molecule in axon guidance and connectivity processes for the establishment of the appropriate premotor circuits in the spinal cord.