Main interests and research lines:
Transcranial Current Stimulation
Transcranial direct-current stimulation (tDCS) is a non-invasive brain stimulation technique that has been successfully applied for modulation of cortical excitability. The medical interest in the use of this technique is growing as a cheap non-invasive tool for basic and clinical research in various neurologic pathologies, including chronic pain, stroke, and depression. tDCS is capable of inducing changes in neuronal membrane potentials in a polarity-dependent manner. When tDCS is of sufficient length, synaptically driven after-effects are induced. Nevertheless, the mechanisms underlying these after-effects are largely unknown.
At present I'm involved in the development of new animal models for testing the immediate effects and after-effects induced by transcranial current stimulation (direct current tDCS and alternating current tACS) in different cortical areas and to explore the mechanisms underlying the induced neural changes. This work is carried out in the context of FP7 European project titled “Hyper Interaction Viability Experiments” (HIVE). In a recent paper we show that tDCS applied over the somatosensory cortex of rabbits is able to modulate tactile perception in a polarity-dependent manner (Márquez-Ruiz et al., 2012 PNAS USA). This effect last for many minutes after cathodal current application when longer stimulation periods are applied. Consistently, the acquisition of classical eyeblink conditioning is potentiated or depressed when simultaneous anodal or cathodal current is applied over the somatosensory cortex. We also show that blocking the activation of adenosine A1 receptors prevents the long-term depression (LTD) evoked in the somatosensory cortex after cathodal tDCS, indicating that the selective pharmacologic manipulation of adenosine receptors during simultaneous tDCS may have important clinical applications.
In collaboration with the research team directed by Fabrice Wendling (France) we recently published a novel computational model, based on experimental results from rabbits, in order to investigate the local effects of tDCS on cortical neuronal populations (Malaee-Ardekani et al., 2012 Brain Stimul).
Learning and Memory
Neural mechanisms underlying learning and memory processes constitute one of the most fascinating topics in modern neurosciences. Synaptic plasticity occurring at different places in the brain in the form of long-term plasticity (long-term potentiation and depression) has been proposed as the neural substrate to store acquired learning abilities.In particular, I’m interested in the role of motor and cerebellar cortices in motor task learning.
Up to now, in vitro studies have supported the occurrence of long-term depression (LTD) in the cerebellum, an interaction between the parallel fibers and Purkinje cells (PC) that requires the combined activation of the parallel and climbing fibers. Very recently, in collaboration with PhD. Guy Cheron (Université Libre de Bruxelles, Belgium), I investigated the existence of LTD plasticity in alert mice by using electrical stimulation of the whisker pad. We found that LTD occurred in the N3 local field potential (LFP) component (amplitude decrease and delayed latency), after 10 min of whisker stimulation at a frequency of 8 Hz. The LFP N2-N3 component coincided with the early evoked simple spikes (SS) of the PC, and was followed by an evoked complex spike (CS); this conjugated activation of the PC was reinforced during the 8 Hz-stimulation (Márquez-Ruiz and Cheron, 2012 PLoS One). This result provided the first demonstration that LTD can be induced in the cerebellum of alert animals in response to sensory peripheral input.
Motor control during sleep
Mammalian sleep is not a homogenous state, and different variables have traditionally been used to distinguish different periods during sleep. Of these variables, eye movement is one of the most paradigmatic, and has been used to differentiate between the so-called rapid eye movement (REM) and non-REM (NREM) sleep periods. Despite this, eye movements during sleep are poorly understood, and the behaviour of the oculomotor system remains almost unknown.
During last years, in collaboration with PhD. Miguel Escudero (University of Seville, Spain), I have tried to characterize the behavior of the oculomotor systems during spontaneous and pharmacologically induced sleep. Thanks to a precise description of eye movements (Márquez-Ruiz and Escudero, 2008 J Physiol-London) and the behavior of extraocular motoneurons (Escudero and Márquez-Ruiz, 2008 J Physiol-London) during the wake–sleep cycle, we showed that the oculomotor system is controlled by tonic and phasic signals that fully explain eye movements during sleep. Tonic inhibition and a complex pattern of bilateral activation–inhibition of extraocular motoneurons are responsible for the exclusive characteristics of rapid eye movements during sleep.
In addition, we demonstrated in recent papers that microinjection of carbachol in the nucleus reticularis pontis oralis (NRPO) seems to activate the structures responsible for the exclusive oculomotor behavior observed during REM sleep, validating this pharmacological model and enabling a more efficient exploration of phasic and tonic phenomena underlying eye movements during REM sleep (Márquez-Ruiz and Escudero, 2009 SLEEP). In contrast, the cholinergic activation of the nucleus reticularis pontis oralis (NRPC) induces oculomotor phenomena that are somewhat similar to those described during REM sleep (Márquez-Ruiz and Escudero, 2010 SLEEP). The precise comparison of the dynamics and timing of the eye movements induced by NRPC activation further suggests that a temporal organization of both NRPCs is needed to reproduce the complexity of the oculomotor behavior during REM sleep.