Miguel Ángel Morales Mendoza

2. Investigamos la plasticidad sináptica responsable de la potenciación a largo plazo (LTP) en la sinapsis ganglionar simpática y su participación en procesos de disfunción del sistema nervioso simpático.

También investigamos los mecanismos de plasticidad sináptica, particularmente los de LTP, una propiedad neuronal descrita originalmente en el hipocampo y relacionada con la memoria y el aprendizaje. A partir de mis estudios de doctorado en los que demostré por primera vez la presencia de LTP en la sinapsis ganglionar in vivo en felinos, he continuado investigando sobre este tema lo que ha llevado a nuestro grupo a postular un modelo de neuromodulación pre y postsináptica que involucra la co-transmisión para explicar la LTP ganglionar. También hemos demostrado que la LTP ganglionar puede ser modulada por neurotrofinas y recientemente completamos un estudio sobre las vías y canales intracelulares involucrados (como el KCNQ) en la modulación de LTP por neurotrofinas. Como en el caso de nuestro trabajo sobre segregación de transmisores, en este caso nos hemos propuesto estudiar si la LTP se modifica en condiciones de disfunción simpática y si GABA participa en estas variaciones. Recientemente publicamos que la HTA modifica la LTP no solo cuando la hipertensión se ha manifestado, sino en etapas previas a la expresión de la hipertensión. Actualmente estamos investigando si la LTP está alterada en otra patología de disfunción simpática como el síndrome metabólico.

In English

COMMUNICATION AND NEURONAL PLASTICITY

1. We study the co-transmission and segregation of transmitters in control and dysfunction conditions of the sympathetic nervous system.

Synaptic co-transmission is the property that neurons have of using two or more transmitters to chemically communicate with each other. When synaptic co-transmission was found in the 1960s, it was established that neurons stored and released the same combination of transmitters in all their synapses. This co-localization mechanism was accepted until the 1990s when some work groups including ours discovered that neurons, in addition to co-localize their transmitters, have the ability to distribute, store and release them separately at their different synapses i.e. we find that in neuronal co-transmission, in addition to the co-localization, there is also a segregation of transmitters. This neuronal ability to store and presumably release different sets of transmitters from individual synaptic terminals allows, among other things, to expand the range of interactions between neurons.

By using the synapse of the peripheral ganglia of sympathetic autonomic neurons, we showed that segregation, like other neuronal processes, shows plasticity, that is, segregation can modify its proportion and distribution according to the requirements of the neuronal environment. First, we found the plasticity of segregation at the experimental level through modifying the presence of neurotrophins, then we explored whether the plasticity of segregation also occurred in pathophysiological changes of sympathetic function. We analyzed stress and arterial hypertension (HT) and find that in effect the segregation of the transmitters acetylcholine and GABA varies in these conditions of sympathetic dysfunction. We are currently investigating whether segregation changes with age and in another pathology that compromises sympathetic function, that in recent times has gained great relevance, the metabolic syndrome.

2. We investigated the synaptic plasticity responsible for long-term potentiation (LTP) in the sympathetic ganglionic synapsis and its participation in processes of sympathetic nervous system dysfunction.

We also investigate the mechanisms of synaptic plasticity, particularly those of LTP, a neuronal property originally described in the hippocampus and related to memory and learning. From my doctoral studies where I demonstrated for the first time the presence of LTP in the ganglionic synapsis in vivo, I have continued research on this subject which has led our group to postulate a pre and postsynaptic neuromodulation model that involves co- transmission to explain ganglionic LTP. We have also shown that ganglionic LTP can be modulated by neurotrophins and we recently completed a study on the intracellular pathways and channels involved (such as KCNQ) in the modulation of LTP by neurotrophins. As in the case of our work on transmitter segregation, in this case we have proposed to study whether LTP is modified under conditions of sympathetic dysfunction and if GABA participates in these variations of LTP. Recently we published that the HT modifies the LTP not only when the hypertension has manifested, but in stages prior to the expression of the hypertension. We are currently investigating whether LTP is altered in another pathology of sympathetic dysfunction such as metabolic syndrome.