One of the essential requirements for accurate functioning of the nervous system is that synaptic connections are formed and neural circuits are assembled with precision. Two major contributors to the establishment of selective synapse formation are thought to be the positional and molecular identities of neurons. In many instances, the fine-grained precision of synaptic connectivity is thought to occur through a process of molecular recognition that depends on the interaction of complementary recognition molecules expressed on pre- and post-synaptic partners. However, the lack of experimental observations suggests that this is perhaps not the predominant mechanism used in assembling neural networks. In addition to molecular recognition mechanisms, the range of alternative postsynaptic targets can be reduced by organized patterns of neuronal position and axonal growth and termination to deliver the terminals of appropriate pre- and postsynaptic partners to restricted volumes of the developing nervous system. Thus, the positional identities of neurons carry significance in establishing neural networks. The selectivity with which sensory axons form connections with spinal motor neurons drives coordinated motor behavior. The precise profile of monosynaptic sensory-motor connectivity has been suggested to have its origins in the recognition of motor neuron subtypes by group Ia sensory afferents. Here I present an analysis of sensory-motor connectivity patterns in mice in which the normal clustering and positioning of motor neurons has been scrambled through genetic manipulations to conditionally knock out the transcription factor FoxP1. FoxP1, together with an intricate network of Hox genes, drives molecular differentiation programs that give rise to the molecular diversity observed in limb level motor neurons. Conditional ablation of FoxP1 in motor neurons causes scrambling of the motor neurons as well as normalization of molecular identity among all limb level motor neurons. My findings in the conditional FoxP1 mutant mice indicate that critical steps in the patterning of sensory-motor connectivity are governed more by the dorsoventral position of motor neurons than by their identity. My findings imply that sensory-motor specificity in monosynaptic reflex arcs depends on the ability of group Ia sensory afferents to target discrete dorsoventral domains of the spinal cord in a manner that is independent of motor neuron subtype identities, and even of motor neurons themselves. Motor pool clustering and positioning may therefore have evolved to ensure that the motor neurons that innervate a specific limb muscle are able to receive synaptic input from the group Ia sensory afferents supplying the same muscle.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/D80V8KS1 |
| Date | January 2012 |
| Creators | Surmeli, Gulsen |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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