Ph.D.: Complutense University and Cajal Institute, Madrid,
Spain, 1987
Research Interests
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
Selected Publications
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. |
