Neurobiology of mental, neurodegenerative and neuro-oncological diseases

– EMBRIOLOGÍA EXPERIMENTAL :
Mediante manipulaciones en embriones de ratón y pollo estudiamos los
factores celulares y moleculares que dirigen la regionalización del
tubo neural, la proliferación, la diferenciación y la migración celular en el Sistema Nervioso Central. Nos centramos en el análisis de las moléculas que controlan el desarrollo y la actividad citogenética de los organizadores secundarios en el encéfalo, como son Shh, Wnts y Fgfs, en el organizador ístmico (IsO), en la zona limitans intratalámica (ZLI) y el organizador anterior (ANR).

– NEUROGENÉTICA :
Estudiamos las expresiones de genes importantes en la organización
estructural del cerebro a lo largo del desarrollo. Las manipulaciones
experimentales, el estudio de mutantes y de ratones knock-out nos
permiten conocer el papel funcional de estos genes.
Anlizamos también genes humanos de importancia en mutaciones que cursan con: Lisencefalia/ heterotopias corticales , esclerosis múltiple y neuropatías periféricas sensitivo-motoras, así como el síndrome de Down. Estudiamos genes implicados en el desarrollo cortical en pacientes con psicosis funcionales (esquizofrenia y procesos bipolares).

– CÉLULAS MADRE :
Estamos desarrollando modelos experimentales que permiten de mostrar la potencialidad neural de células madre de la médula ósea, sobretodo de tipo hematopoyético. En modelos animales de enfermedades
desmielinizantes (esclerosis múltiple) y neurodegenerativas (ataxia
cerebelo espinal y esclerosis lateral amiotrófica) estamos observando
que las células madre hematopoyéticas tienen un efecto trófico y
parcialmente regenerativo.

Lines of investigation Dr. Emilio Geijo:

1. The study of the basic physiological mechanisms of the cortical local circuits, and in particular of the prefrontal cortex circiuts; this cortical area is implicated in several cognitive functions, including a crucial role in the working memory. Also, prefrontal cortex is densely innervated by dopaminergic and serotoninergic fibres arising in diencephalon and brain stem which participate in the control of cortical functions. We currently use intracellular recordings with microelectrodes and patch electrodes from cortical pyramidal neurons visually identified with infrared differential interference contrast microscopy (IR-DIC) and we measure membrane potential and currents and synaptic responses. The main lines of work are the study of:

a. The intrinsic electrophysiological properties of cortical neurons, the voltage-dependent ionic currents and their modulation by dopamine.
b. The mechanisms of excitatory and inhibitory synaptic transmission at the level of local circuits, their modulation by dopamine and the role of intrinsic electrophysiological properties on the processes of synaptic integration.
c. The electrophysiology of the cerebral cortex of a genetically modified mouse that is a model of a human disease (the mutant mouse of the gene Lis1; the mutations of the LIS1 gene in man produce lissencephaly). This line of research is conducted as a collaboration with Dr. Salvador Martínez, from the Unit of Development of the IN:

2. The physiology of the type I cells of the carotid body; these are quimioreceptor cells and are sensitive to the O2 and CO2 partial pressure and to the blood pH. We use current and membrane potential recordings with patch electrodes from dissociated cells from the carotid body kept in primary cultures. The main lines of work are the study of:

a. The calcium currents present in the cell membrane and their role in the secretion of catecholamines.
b. The effect of natural stimuli and of several metabolic venoms on the electrical responses of these cells.