Francisco J. Alvarez

Our lab is interested in the development of synaptic circuits in the spinal cord. Newborns express immature spinal circuits reflected in abnormal reflexes and limited capacity to make effective postural adjustments or fine movements. The neurobiological principles that drive the postnatal maturation of spinal cord motor circuits, in particular the development of inhibitory synapses and interneurons that modulate motoneuron activity are largely unknown. Our laboratory uses electron microscopy, confocal microscopy and electrophysiological methods to study the postnatal maturation of structure, molecular composition and synaptic function of key inhibitory circuits in the spinal cord.
Much of our work in recent years concentrated on the differential recruitment of glycine receptors, GABAA receptors and the protein gephyrin to the postsynaptic densities of inhibitory synapses on different spinal cord neurons. For example, one type of interneuron denominated the Renshaw cell expresses inhibitory synapses with rich gephyrin clusters and large postsynaptic areas. These synapses cluster glycine receptors and a a3-5b3g2 containing GABAA receptors. In contrast, motoneurons display inhibitory synapses with small gephyrin clusters containing glycine receptors and a a2b3g2 GABAA receptors. In our work we characterize this variability, investigate its functional significance and use experimental manipulations in vivo to study how it is generated during circuit maturation. Our quantitative analyses of receptor clustering on central neurons developed in several international collaborations with laboratories in Canberra (Australia), Seville (Spain), Madrid (Spain), London (UK) and Quebec (Canada) as well as in the US (MCO, Toledo, Ohio).
Our latest work uses transgenic mouse models developed by Dr. Martyn Goulding (Salk Institute) to analyze the postnatal specification of adult inhibitory interneurons from embryonic spinal neuronal groups. Using transgenic mice that carry linage markers for the subpopulation of embryonic neurons derived from the V1 group, we have shown that several different types of segmental ventral inhibitory adult interneurons derive from this group and therefore share a similar genetic background. Thus, we are currently investigating other factors that could influence the process of differentiation of V1-derived interneurons into the different major subclasses of ventral inhibitory interneurons.