Francisco J. Alvarez, Ph.D.
Ph.D.: Complutense University and Cajal Institute, Madrid, Spain, 1987
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.
See also: Excitatory/Inhibitory Balance
Gonzalez-Forero D, Alvarez FJ (2005) Differential postnatal maturation of GABAA1, glycine receptor and mixed synaptic currents in Renshaw cells. J Neurosci 25:2010-2023.
Gonzalez-Forero D, Pastor AM, Geiman EJ, Benitez-Termiño B, Alvarez FJ (2005) Regulation of gephyrin cluster size and inhibitory synaptic currents on Renshaw cells by motor axon excitory inputs. J Neurosci 25:417-420.
Alvarez FJ, Jonas P, Sapir T, Hartley R, Geiman EG, Todd A, Goulding M (2005) Postnatal phenotype and localization of spinal cord V1 derived interneurons. J Comp Neurol 493:177-192.
Mentis GZ, Alvarez FJ, Bonnot A, Richards DS, Gonzalez-Forero D, Zerda R, O'Donovan MJ (2005) Non-cholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord. PNAS 102: 7433-7349.
Gonzalez-Forero D, Morcuende SR, Alvarez FJ, de la Cruz RR, Pastor AM (2005) Transynaptic functional effects of tetanus neurotoxin in the oculomotor system. Brain 128:2175-2188.
Richards DS, Villalba RM, Alvarez FJ, Stern JE (2005) Cell-type difference in the expression of GABAB receptors in magnocellular neurosecretory cell of male, virgin female and lactating rats. J Neuroendocrinol 17:413-423.
Lilly SM, Alvarez FJ, Tietz EI (2005) Synaptic and subcellular localization of AKAP150 in rat hippocampal CA1 pyramidal cells: co-localization with exciatory synaptic markers. Neuroscience 134:155-163.
Alvarez FJ, Villalba RM, Zerda R, Schneider SP (2004) Vesicular glutamate transporters in the spinal cord with special reference to sensory primary afferent synapses. J Comp Neurol 472:259-282.
Sapir T, Geiman EJ, Wang Z, Velasquez T, Frank E, Alvarez FJ, Goulding M (2004) Pax6 and En1 regulate two critical aspects of Renshaw cell development. J Neurosci 24:1255-1264.
Gonzalez-Forero D, Pastor AM, Delgado-Garcia JM, De la Cruz RR, Alvarez FJ (2004) Synaptic structural modification following changes in activity induced by tetanus neurotoxin in abducens neurons. J Comp Neurol 471:201-218.
Aguayo LG, van Zundert B, Tapia JC, Carrasco MA, Alvarez FJ (2004)
Changes on the properties of glycine receptors during development. Brain Res Reviews 47:33-45.
van Zundert B, Alvarez FJ, Tapia JC, Yeh HH, Diaz E, Aguayo LG (2004)
Developmental-dependent action of microtubule depolymerization on the function and structure of synaptic glycine receptor clusters in spinal neurons. J Neurophysiol 91:1036-1094.
Previous key papers include:
Alvarez FJ, Kavookjian AM, Light AR (1992) Synaptic interactions between GABA-immunoreactive profiles and the terminals of functionally defined myelinated nociceptors in the monkey and cat spinal cord. J Neurosci 12:2901-2917.
Alvarez FJ, Dewey DE, Harrington DA, and Fyffe REW (1997) Cell-type specific organization of glycine receptor clusters in the mammalian spinal cord. J Comp Neurol 379:150-169.
Alvarez FJ, Dewey DE, McMillin P, Fyffe REW (1999) Distribution of cholinergic contacts on Renshaw cells in the rat spinal cord. J Physiol 512:787-797.
Lim R, Alvarez FJ, Walmsley B (1999) Quantal size is determined by receptor cluster area at glycinergic synapses in the rat brainstem. J Physiol 516:505-512.
Geiman EJ, Knox MC, Alvarez FJ (2000) Postnatal maturation of gephyrin/glycine receptor clusters on spinal cord Renshaw cells. J Comp Neurol 426:130-142.
Geiman EJ, Zheng W, Fitschy J-M, Alvarez FJ (2002) Co-localization and molecular composition of GABAa and glycine receptors inside gephyrin patches postsynaptic to glycine or mixed GABA-glycine synapses on Renshaw cells. J Comp Neurol 444:275-289.