Loss of ETV1/ER81 in Motor Neurons Leads to Reduced Monosynaptic Inputs From Proprioceptive Sensory Neurons

Document Type

Article

Publication Date

3-2023

Abstract

Abstract

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Presynaptic inputs determine the pattern of activation of postsynaptic neurons in a neural circuit. Molecular and genetic pathways that regulate the selective formation of subsets of presynaptic inputs are largely unknown, despite significant understanding of the general process of synaptogenesis. In this study, we have begun to identify such factors using the spinal monosynaptic stretch reflex circuit as a model system. In this neuronal circuit, Ia proprioceptive afferents establish monosynaptic connections with spinal motor neurons that project to the same muscle (termed homonymous connections) or muscles with related or synergistic function. However, monosynaptic connections are not formed with motor neurons innervating muscles with antagonistic functions. The E26 transformation-specific (ETS) transcription factor ER81 (also known as ETV1) is expressed by all proprioceptive afferents, but only a small set of motor neuron pools in the lumbar spinal cord of the mouse. Here, we use conditional mouse genetic techniques to eliminate Er81 expression selectively from motor neurons. We find that ablation of Er81 in motor neurons reduces synaptic inputs from proprioceptive afferents conveying information from homonymous and synergistic muscles, with no change observed in the connectivity pattern from antagonistic proprioceptive afferents. In summary, these findings suggest a role for ER81 in defined motor neuron pools to control the assembly of specific presynaptic inputs and thereby influence the profile of activation of these motor neurons.

NEW & NOTEWORTHY In the stretch reflex circuit, proprioceptive afferents establish monosynaptic connections with spinal motor neurons that project to the same muscle. The ETS transcription factor ETV1/ER81 is expressed in all proprioceptive afferents, but only certain groups of motor neurons in the spinal cord of the mouse. Conditional ablation of Er81 expression from motor neurons reveals selective defects in the establishment of stretch reflex connections within motor pools that would normally express Er81.

DOI

10.1152/jn.00172.2022

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