CONICET | Buscador de Institutos y Recursos Humanos

Locomotor activity in mammals is generated by neural networks known as central pattern generators (CPGs), which are comprised of interneurons located in the ventromedial spinal cord. Genetic characterization of transcription factor expression at early embryonic time points has led to the identification of discrete interneuronal populations in the central nervous system. Electrophysiological analysis of the firing properties of these populations allow for the identification of component interneurons of the locomotor CPG. We have focussed our study on Dbx1-derived interneurons as well as a small population of closely related cells that differentiate from Lbx1-expressing progenitors. These cells are located in lamina VIII of the postnatal mouse spinal cord and can be subdivided into at least 4 genetically distinct subpopulations, each potentially playing a unique role in the production of locomotor behavior. In an initial approach, we performed targeted whole-cell patch-clamp recording from these neurons and demonstrated, that taken together, they display one of three distinct sets of electrophysiological properties. Approximately 15% are rhythmically active during fictive locomotion and likely inhibit contralateral motor neurons. Approximately 45% oscillate during fictive locomotor activity and display conditional bursting properties. These interneurons are candidate rhythm-generating components of the locomotor CPG. Neuronal activity in the remaining cells is unrelated to fictive locomotion. In this project we perform patch-clamp recording as well as population recordings based on multiphoton/confocal Ca2+ imaging using the membrane-permeant dye Fluo-8-AM. These experiments allow us to investigate the intrinsic firing properties of each specific genetic subpopulation and provide insights into the structure and mechanism of function of the locomotor CPG.