RIG:Identification of Pacemaker Neurons Controlling Locomotor Behavior

University Of Puerto Rico Medical Sciences Campus, San Juan PR

Investigators

Abstract

The basic motor signals that direct limb movements during walking (locomotion) are generated by circuits of neurons called central pattern generators (CPGs) which are located within the spinal cord. Networks of interneurons control the activity of motor neurons which send signals that control muscles that produce flexion and extension movements in both sides of the body to generate the normal alternating gait seen during locomotion. The identity and contribution of defined interneuron populations to mammalian locomotor behaviors is poorly understood. It has been suggested that ipsilateral excitatory interneurons (IINs), those whose nerve fibers (axons) do not cross the spinal cord midline, are involved in the generation and maintenance of locomotion. This research project will use the neonatal mouse spinal cord preparation to identify IINs which are believed to initiate the locomotor pattern (termed pacemaker neurons). The timing and pattern of the firing properties of IINs will be electrophysiologically recorded and assessed during a drug-induced locomotor-like motor pattern using serotonin (5-HT) and glutamate (known to be essential for producing locomotion in mammals). Additionally, pacemaker-like properties in the IINs will be identified based on the effects of 5-HT and glutamate on the IINs intrinsic membrane properties. Finally, the effects of 5-HT and glutamate on the flow of calcium (essential for the release of neurotransmitters during behaviors such as locomotion) through voltage-activated calcium channels of the IINs will be assessed using fluorescent dyes sensitive to calcium and visualized using fast confocal microscopy. This study will provide a better understanding of important general principles for how neuronal populations and their membrane properties interact to shape motor behaviors such as locomotion. The research projects conducted will provide training opportunities to undergraduate and graduate-level students from under-represented minority groups by engaging and exposing them to state-of-the-art anatomical, physiological and biophysical research techniques using the mouse spinal cord as their research model.