Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB302

Poster Communications

Feedforward and internal feedback motor circuit dysfunction impairs reaching movements in EphA4 knockout mice

J. Jiang1

1. Department of Integrative Medical Biology, Section of Physiology, Umea University, Umea, Sweden.

Skilled reaching movements are thought to be initiated by feedforward motor commands conveyed by supraspinal motor pathways1, and modified by peripheral feedback as well as internal feedback systems that transmit copies of motor commands to cerebellar circuits for rapid online updating2,3. Mutation of the axon guidance molecule EphA4 has been shown to produce axonal misrouting of the corticospinal tract4 and spinal interneurons5. Mice lacking EphA4 receptors display a specific motor deficit, a rabbit-like hopping gait in hind limbs4. However, it remains unknown whether the loss of EphA4 signaling disrupts the function of forelimb motor circuits and the execution of dexterous movements. In this study, we use behavioral and in vivo electrophysiological techniques to investigate how loss of EphA4 function affects feedforward command and internal feedback neural circuits that influence forelimb motor neurons (MNs) and the execution of skilled forelimb movements. We show that EphA4 knockout mice display an impairment in goal-directed reaching. We demonstrate that cortico-reticulospinal excitation of forelimb MNs is increased, whereas direct reticulospinal excitation of MNs is decreased in EphA4 knockout mice. We further identify reduced direct propriospinal neurons excitation of forelimb MNs and dysfunction in the lateral reticular nucleus - cerebellar pathway in EphA4 knockout mice. Together, our findings reveal that loss of EphA4 produces abnormal transmission in both descending feedforward command pathways as well as ascending internal feedback pathways, resulting in impaired reaching movements.

Where applicable, experiments conform with Society ethical requirements