Jose Maria Delgado Garcia | Universidad Pablo de Olavide (original) (raw)

Papers by Jose Maria Delgado Garcia

Frontiers in Systems Neuroscience, Jan 28, 2021

Frontiers in Neuroanatomy, Mar 13, 2023

Frontiers in Neuroscience, Jun 26, 2023

HAL (Le Centre pour la Communication Scientifique Directe), Aug 6, 2010

Scientific Reports, Feb 3, 2021

Molecular Autism

Background Fragile X syndrome (FXS), the most common inherited intellectual disability, is caused... more Background Fragile X syndrome (FXS), the most common inherited intellectual disability, is caused by the loss of expression of the Fragile X Messenger Ribonucleoprotein (FMRP). FMRP is an RNA-binding protein that negatively regulates the expression of many postsynaptic as well as presynaptic proteins involved in action potential properties, calcium homeostasis and neurotransmitter release. FXS patients and mice lacking FMRP suffer from multiple behavioral alterations, including deficits in motor learning for which there is currently no specific treatment. Methods We performed electron microscopy, whole-cell patch-clamp electrophysiology and behavioral experiments to characterise the synaptic mechanisms underlying the motor learning deficits observed in Fmr1KO mice and the therapeutic potential of positive allosteric modulator of mGluR4. Results We found that enhanced synaptic vesicle docking of cerebellar parallel fiber to Purkinje cell Fmr1KO synapses was associated with enhanced a...

bioRxiv (Cold Spring Harbor Laboratory), Apr 30, 2022

Journal of Visualized Experiments, 2018

EMBO Molecular Medicine, 2019

Brain, 2019

See Brouillet and Merienne (doi:10.1093/brain/awz274) for a scientific commentary on this article... more See Brouillet and Merienne (doi:10.1093/brain/awz274) for a scientific commentary on this article.Creus-Muncunill et al. report that protein translation is altered in the striatum of Huntington’s disease mouse models, with upregulated expression of proteins from ribosomal and oxidative phosphorylation pathways. Pharmacological normalization of protein translation in R6/1 mice ameliorates motor disturbances and normalizes ribosomal content in the striatum.

Frontiers in Neuroscience, 2019

Scientific Reports, 2018

Spike sorting is one of the most important data analysis problems in neurophysiology. The precisi... more Spike sorting is one of the most important data analysis problems in neurophysiology. The precision in all steps of the spike-sorting procedure critically affects the accuracy of all subsequent analyses. After data preprocessing and spike detection have been carried out properly, both feature extraction and spike clustering are the most critical subsequent steps of the spike-sorting procedure. The proposed spike sorting approach comprised a new feature extraction method based on shape, phase, and distribution features of each spike (hereinafter SS-SPDF method), which reveal significant information of the neural events under study. In addition, we applied an efficient clustering algorithm based on K-means and template optimization in phase space (hereinafter K-TOPS) that included two integrative clustering measures (validity and error indices) to verify the cohesion-dispersion among spike events during classification and the misclassification of clustering, respectively. The proposed...

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 2, 2018

Rapid and effective neural transmission of information requires correct axonal myelination. Modif... more Rapid and effective neural transmission of information requires correct axonal myelination. Modifications in myelination alter axonal capacity to transmit electric impulses and enable pathological conditions. In the central nervous system (CNS), oligodendrocytes (OLs) myelinate axons, a complex process involving various cellular interactions. However, we know little about the mechanisms that orchestrate correct myelination. Here, we demonstrate that OLs express R-Ras1 and R-Ras2. Using female and male mutant mice to delete these proteins, we find that activation of the PI3K/Akt and Erk1/2-MAPK pathways is weaker in mice lacking one or both of these GTPases, suggesting that both proteins coordinate the activity these two pathways. Loss of R-Ras1 and/or R-Ras2 diminishes the number of OLs in major myelinated CNS tracts and increases the proportion of immature OLs. In and null mice, OLs show aberrant morphologies and fail to differentiate correctly into myelin-forming phenotypes. The s...

Scientific reports, Jan 21, 2017

While movie edition creates a discontinuity in audio-visual works for narrative and economy-of-st... more While movie edition creates a discontinuity in audio-visual works for narrative and economy-of-storytelling reasons, eyeblink creates a discontinuity in visual perception for protective and cognitive reasons. We were interested in analyzing eyeblink rate linked to cinematographic edition styles. We created three video stimuli with different editing styles and analyzed spontaneous blink rate in participants (N = 40). We were also interested in looking for different perceptive patterns in blink rate related to media professionalization. For that, of our participants, half (n = 20) were media professionals, and the other half were not. According to our results, MTV editing style inhibits eyeblinks more than Hollywood style and one-shot style. More interestingly, we obtained differences in visual perception related to media professionalization: we found that media professionals inhibit eyeblink rate substantially compared with non-media professionals, in any style of audio-visual edition.

PloS one, 2017

This article explores whether there are differences in visual perception of narrative between the... more This article explores whether there are differences in visual perception of narrative between theatrical performances and screens, and whether media professionalization affects visual perception. We created a live theatrical stimulus and three audio-visual stimuli (each one with a different video editing style) having the same narrative, and displayed them randomly to participants (20 media professionals and 20 non-media professionals). For media professionals, watching movies on screens evoked a significantly lower spontaneous blink rate (SBR) than looking at theatrical performances. Media professionals presented a substantially lower SBR than non-media professionals when watching screens, and more surprisingly, also when seeing reality. According to our results, media professionals pay higher attention to both screens and the real world than do non-media professionals.

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 14, 2017

The prelimbic (PrL) cortex constitutes one of the highest levels of cortical hierarchy dedicated ... more The prelimbic (PrL) cortex constitutes one of the highest levels of cortical hierarchy dedicated to the execution of adaptive behaviors. We have identified a specific local field potential (LFP) pattern generated in the PrL cortex and associated with cognition-related behaviors. We used this pattern to trigger the activation of a visual display on a touch screen as part of an operant conditioning task. Rats learned to increase the presentation rate of the selected θ to β-γ (θ/β-γ) transition pattern across training sessions. The selected LFP pattern appeared to coincide with a significant decrease in the firing of PrL pyramidal neurons and did not seem to propagate to other cortical or subcortical areas. An indication of the PrL cortex's cognitive nature is that the experimental disruption of this θ/β-γ transition pattern prevented the proper performance of the acquired task without affecting the generation of other motor responses. The use of this LFP pattern to trigger an oper...

Cell reports, Jun 6, 2017

The role of neurotrophic factors as endogenous survival proteins for brain neurons remains conten... more The role of neurotrophic factors as endogenous survival proteins for brain neurons remains contentious. In the cerebellum, the signals controlling survival of molecular layer interneurons (MLIs) are unknown, and direct evidence for the requirement of a full complement of MLIs for normal cerebellar function and motor learning has been lacking. Here, we show that Purkinje cells (PCs), the target of MLIs, express the neurotrophic factor GDNF during MLI development and survival of MLIs depends on GDNF receptors GFRα1 and RET. Conditional mutant mice lacking either receptor lose a quarter of their MLIs, resulting in compromised synaptic inhibition of PCs, increased PC firing frequency, and abnormal acquisition of eyeblink conditioning and vestibulo-ocular reflex performance, but not overall motor activity or coordination. These results identify an endogenous survival mechanism for MLIs and reveal the unexpected vulnerability and selective requirement of MLIs in the control of cerebellar-...

Frontiers in Behavioral Neuroscience, 2015

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 2, 2004

An exciting topic regarding integrative properties of the nervous system is how transient motor c... more An exciting topic regarding integrative properties of the nervous system is how transient motor commands or brief sensory stimuli are able to evoke persistent neuronal changes, mainly as a sustained, tonic action potential firing. A persisting firing seems to be necessary for postural maintenance after a previous movement. We have studied in vitro and in vivo the generation of the persistent neuronal activity responsible for eye fixation after spontaneous eye movements. Rat sagittal brainstem slices were used for the intracellular recording of prepositus hypoglossi (PH) neurons and their synaptic activation from nearby paramedian pontine reticular formation (PPRF) neurons. Single electrical pulses applied to the PPRF showed a monosynaptic glutamatergic projection on PH neurons, acting on AMPA-kainate receptors. Train stimulation of the PPRF area evoked a sustained depolarization of PH neurons exceeding (by hundreds of milliseconds) stimulus duration. Both duration and amplitude of t...

Frontiers in Systems Neuroscience, Jan 28, 2021

Frontiers in Neuroanatomy, Mar 13, 2023

Frontiers in Neuroscience, Jun 26, 2023

HAL (Le Centre pour la Communication Scientifique Directe), Aug 6, 2010

Scientific Reports, Feb 3, 2021

Molecular Autism

bioRxiv (Cold Spring Harbor Laboratory), Apr 30, 2022

Journal of Visualized Experiments, 2018

EMBO Molecular Medicine, 2019

Brain, 2019

Frontiers in Neuroscience, 2019

Scientific Reports, 2018

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 2, 2018

Scientific reports, Jan 21, 2017

PloS one, 2017

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 14, 2017

Cell reports, Jun 6, 2017

Frontiers in Behavioral Neuroscience, 2015

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 2, 2004

The long-term effects of botulinum neurotoxin (BoNt) type A injected in the extraocular lateral r... more The long-term effects of botulinum neurotoxin (BoNt) type A injected in the extraocular lateral rectus muscle have been investigated in atort behaving cats. Animals were prepared for the chronic recording of synaptic neu-romuscular field potentials, eye movements, and the un¡tary actívity of identified abducens motoneurons and internuclear neurons. Paraltet tight and electron microscopy and immunohistochemical studies were also carríed out. Single BoNt ¡njections at doses from 0.01 to 0.3 ng/kg (that is, ín the range of those used for thenpeutíc applications) reduced, or even compte-tely eliminated, eye movements in the abducüng directíon for up to two months.These doses did not affectthe discharge profile of inneruating moto-nelJrons, which remained related to the actual movements of the contralate-ral, unparalyzed, eye. This result indicates that abducens motoneurons are still under the ¡nfluence of the oculomotor system when low BoNt doses are applied, and that paralysis per se is not sufficient to initiate axotomy-like neural responses in extraocular motoneurons. Single injections at a dose of 3 ng/kg produced significant changes in the discharge pattern of abducens motoneurons lasting up to six months, the maximum time checked. panllel studies in acute animals showed a loss of synapt¡c ¡nputsto abducens moto-neurons iniected with this high dose of BoNt. H¡stologicalanalyses indicated that there is no cell death, but large ultrastructunl changes that underlie the

The electrophysiological measurement of changes in synaptic strength taking place during the acqu... more The electrophysiological measurement of changes in synaptic strength taking place during the acquisition of new motor and cognitive abilities, and during other physiological conditions, is an excellent tool for studying the role of different receptors and/or ion channels in the nervous system of alert behaving experimental animals. Many different molecular and subcellular components, including their complex mechanisms , have specifi c roles and underlie the physiological basis of learning and memory phenomena. In the past few years, various sophisticated methods (genetically manipulated animals, light stimulation systems, pharmacokinetic protocols, etc.) have emerged as valuable tools to be considered together with the more classic in vivo electrophysiological techniques. Recent methodological and technical (use of multiple recording microelectrodes, telemetric recordings, etc.) improvements will help to refi ne the level of collected results. In addition, new mathematical routines and modeling procedures are also exponentially increasing the level of data analysis and representation. The aim of all these classic and contemporary procedures is, as far as possible, to study motor and cognitive processes in vivo. The present chapter will deal with different stimulating and recording procedures that can be used in alert behaving mammals during the acquisition, retrieval, or extinction of new abilities. Abbreviations EMG Electromyography fEPSP Field excitatory postsynaptic potential HFS High-frequency stimulation LTP Long-term potentiation PSTH Peristimulus time histogram In the past few years, there has been a notable advance in the knowledge of the structure and localization of many different neu-rotransmitter receptors and/or ion channels that are essential for the proper understanding of the specifi c roles of different neuronal structures. Moreover, these functions are currently studied in agrumas@upo.es

1. The effects ofbotulinum neurotoxin (BoTx) injected into the lateral rectus muscle were examine... more 1. The effects ofbotulinum neurotoxin (BoTx) injected into the lateral rectus muscle were examined in alert cats by recording the extracellular activity ofabducens motoneurons during spontaneous eye movements. 2. A single high dose (3 nglkg) of BoTx produced a complete paralysis of abduction that lasted for more than 2 mo. In addition, changes were found in the discharge pattern ofabducens motoneu-rons. Motoneurons discharged steadily at a low firing rate (l5-50 spikes/s), which in some instances showed a complete independence of eye position. Their increases in activity during oN-directed saccades were markedly reduced with respect to controls. The loss ofinhibitory signals for o¡r-directed saccades was even more eüdent.-i. A low dose (0.3 nglkg) of BoTx also produced a paralysis of the lateral rectus muscle that lasted for-I mo. In this case, only minor modifications in the firing characteristics ofabducens moto-neurons were observed. 4. The present findings indicate that the effects of BoTx observed in the discharge pattern of abducens motoneurons might be due not only to target disconnection, but also to a central action of the neurotoxin on the motoneuron.

Many of the physiological and morphological studies aimed at evaluating the dependence of neurons... more Many of the physiological and morphological studies aimed at evaluating the dependence of neurons on their target cells have been performed by sectioning the axons of the afferent neurons as a means of producing the disconnection with thei¡ target. However, axotomy comprises also a cellular lesion. Thus, the effects it produces can reflect complex phenomena in response not only to target disconnection but also to the damage itself. Nevertheless, this type of study has greatly contributed to the understanding of both the regulatory role of the interactions between neurons and the plastic capabilities of the peripheral and central nervous system (CNS) after lesion. Thus, it is well established that axotomy in the peripheral nervous system is generally followed by regeneration and restitution of function. In contrast, ner¡rons in the CNS often die after axonal injury @anon, 1989). The causes of this differential response are still uncertain, although some mechanisms have begun to be envisioned as likely explanations. At present, it is generally accepted that this opposite response is due, at least in part, to the characteristics of the neuronal environment, which are different between peripheral and CNS. Thus, Schwann cells in the peripheral nervous system have been shown to constitute a suitable substrate for regeneration (Ide and Kato, 1990; Waxman, 1989). In addition, the failure of CNS neurons to regenerate does not 41

Journal of Neuroscience, 2016

The dual-specificity tyrosine phosphorylation-regulated kinase DYRK1A is a serine/threonine kinas... more The dual-specificity tyrosine phosphorylation-regulated kinase DYRK1A is a serine/threonine kinase involved in neuronal differentiation and synaptic plasticity and a major candidate of Down syndrome brain alterations and cognitive deficits. DYRK1A is strongly expressed in the cerebral cortex, and its overexpression leads to defective cortical pyramidal cell morphology, synaptic plasticity deficits, and altered excitation/inhibition balance. These previous observations, however, do not allow predicting how the behavior of the pre-frontal cortex (PFC) network and the resulting properties of its emergent activity are affected. Here, we integrate functional, anatomical, and computational data describing the prefrontal network alterations in transgenic mice overexpressing Dyrk1A (TgDyrk1A). Using in vivo extracellular recordings, we show decreased firing rate and gamma frequency power in the prefrontal network of anesthetized and awake TgDyrk1A mice. Immunohistochemical analysis identified a selective reduction of vesicular GABA transporter punctae on parv-albumin positive neurons, without changes in the number of cortical GABAergic neurons in the PFC of TgDyrk1A mice, which suggests that selective disinhibition of parvalbumin interneurons would result in an overinhibited functional network. Using a conductance-based computational model, we quantitatively demonstrate that this alteration could explain the observed functional deficits including decreased gamma power and firing rate. Our results suggest that dysfunction of cortical fast-spiking interneurons might be central to the pathophysiology of Down syndrome.