Abel Sanchez-Jimenez

Consistent Phosphenes Generated by Electrical Microstimulation of the Visual Thalamus. An Experimental Approach for Thalamic Visual Neuroprostheses

Most work on visual prostheses has centered on developing retinal or cortical devices. However, when retinal implants are not feasible, neuroprostheses could be implanted in the lateral geniculate nucleus (LGN) of the thalamus, the intermediate relay station of visual information from the retina to the visual cortex (V1). The objective of the present study was to determine the types of artificial stimuli that when delivered to the visual thalamus can generate reliable responses of the cortical neurons similar to those obtained when the eye perceives a visual image. Visual stimuli {Si} were presented to one eye of an experimental animal and both, the thalamic {RThi} and cortical responses {RV1i} to such stimuli were recorded. Electrical patterns {RThi*} resembling {RThi} were then injected into the visual thalamus to obtain cortical responses {RV1i*} similar to {RV1i}. Visually- and electrically generated V1 responses were compared. Results: During the course of this work we: (i) characterized the response of V1 neurons to visual stimuli according to response magnitude, duration, spiking rate, and the distribution of interspike intervals; (ii) experimentally tested the dependence of V1 responses on stimulation parameters such as intensity, frequency, duration, etc., and determined the ranges of these parameters generating the desired cortical activity; (iii) identified similarities between responses of V1 useful to compare the naturally and artificially generated neuronal activity of V1; and (iv) by modifying the stimulation parameters, we generated artificial V1 responses similar to those elicited by visual stimuli. Generation of predictable and consistent phosphenes by means of artificial stimulation of the LGN is important for the feasibility of visual prostheses. Here we proved that electrical stimuli to the LGN can generate V1 neural responses that resemble those elicited by natural visual stimuli.

Phytoestrogen Metabolism by Adult Human Gut Microbiota

Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed.

Chronic electrical stimulation of transected peripheral nerves preserves anatomy and function in the primary somatosensory cortex.

The structure and function of the central nervous system strongly depend on the organization and efficacy of the incoming sensory input. A disruption of somesthetic input severely alters the metabolic activity, electrophysiological properties and even gross anatomical features of the primary somatosensory cortex. Here we examined, in the rat somatosensory cortex, the neuroprotective and therapeutic effects of artificial sensory stimulation after irreversible unilateral transection of a peripheral sensory nerve (the infraorbital branch of the trigeminal nerve). The proximal stump of the nerve was inserted into a silicon tube with stimulating electrodes, through which continuous electrical stimulation was applied for 12 h/day (square pulses of 100 μs, 3.0 V, at 20 Hz) for 4 weeks. Deafferented animals showed significant decreases in cortical evoked potentials, cytochrome oxidase staining intensity (layers II–IV), cortical volume (layer IV) and number of parvalbumin‐expressing (layers II–IV) and calbindin‐D28k‐expressing (layers II/III) interneurons. These deafferentation‐dependent effects were largely absent in the nerve‐stimulated animals. Together, these results provide evidence that chronic electrical stimulation has a neuroprotective and preservative effect on the sensory cortex, and raise the possibility that, by controlling the physical parameters of an artificial sensory input to a sectioned peripheral nerve, chronically deafferented brain regions could be maintained at near‐‘normal’ conditions. Our findings could be important for the design of sensory neuroprostheses and for therapeutic purposes in brain lesions or neural degenerative processes.

Thalamic visual neuroprostheses: Comparison of visual percepts generated by natural stimulation of the eye and electrical stimulation of the thalamus

Thalamic visual neuroprostheses to be implanted in the lateral geniculate nucleus of the thalamus (the intermediate relay station of visual information from the retina to the cortex) could be used to provide visual information to blind people when retinal implants are not feasible. The main objective of the present work was to (i) determine a way to compare visual percepts generated by electrical stimulation of the thalamus and percepts elicited by natural stimulation of the eye and (ii) apply this method to contrast the responses of the cortical neurons under these two conditions.

Analysis of gene expression of bifidobacteria using as the reporter an anaerobic fluorescent protein

ObjectivesTo determine the effectiveness of evoglow-Pp1 as a reporter to study gene expression in bifidobacteria. To choose a strong and constitutive promoter to track fluorescently labelled bifidobacteria in environments under anaerobic conditions.ResultsThe elongation factor P (EF-P) promoter from Bifidobacterium longum CECT 4551 produced the highest emission of fluorescence signal and was therefore able to produce the highest gene expression of the promoters studied. The promoters from B. longum CECT 4551 showed different fluorescence signal intensities which, in descending order, were: EF-P, initiation factor IF-2, elongation factor G, elongation factor Tu, elongation factor Nus A, elongation factor Ts and 30S ribosomal protein S12.ConclusionsThe consistency of the methods employed (fluorescence imaging system, fluorescence microscopy, fluorimetry and flow cytometry) showed that the construction pNZ:Prom.GFPana contained the anaerobic fluorescent protein evoglow-Pp1 could be exploited as a tool for analysing the gene expression in bifidobacteria strains.

Structural preservation of deafferented cortex induced by electrical stimulation of a sensory peripheral nerve

Any manipulation to natural sensory input has direct effects on the morphology and physiology of the Central Nervous System. In the particular case of amputations, sensory areas of the brain undergo degenerative processes with a marked reduction in neuronal activity and global disinhibition. This is probably due to a deregulation of the circuits devoted to the control of the cortical activity. These changes are detected in the organization of the representational maps, the metabolic labeling by 2-deoxyglucose or cytochrome oxidase, the density of afferent and efferent axonal connections and the reduced expression of inhibitory neurotransmitters. In the present study, performed in animals, we have evaluated the therapeutic potential of Brain Machine Interfaces in reversing or limiting the degenerative/deregulation processes of amputations. Applying electrical stimulation on amputated peripheral nerves, we have achieved to maintain in approximately normal values 1) the cortical activity and 2) the expression of GABA-associated molecules of the inhibitory interneurons of the primary somatosensory cortex.

Single unit oscillations in rat trigeminal nuclei and their control by the sensorimotor cortex.

Oscillatory activity at both the single and multiunit levels has been reported in most central nervous system structures, and is postulated as a key factor in information processing and coding. Rats provide an excellent model for oscillation-based information processing, since tactile perception of the environment is achieved by rhythmic movements of their whiskers and information-related rhythmic activity has been identified in the thalamus and cortex. However, rhythmic activity related to information processing has never been reported in the sensory trigeminal complex (STC), the first brain stem relay station for whisker-related tactile information. In the present work, we demonstrate the existence of neural oscillations in the vibrissae-related neurons of the nuclei principalis (Pr5), oralis (Sp5o), interpolaris (Sp5i) and caudalis (Sp5c). Rhythmic activity was associated with the main task of each nucleus, prominent in nuclei responsible for tactile vibrissae information processing (up to 17% oscillating neurons in Pr5 and 26% in Sp5i) and less conspicuous in those concerned with pain (8% oscillating neurons in Sp5o and in Sp5c). The higher percentage of oscillating neurons and higher frequencies in Sp5i than in Pr5 suggests an active role for rhythmic activity in integrating multivibrissa inputs. Oscillations are generated within the brainstem; data obtained from decorticated animals suggest the existence of a differential cortical control of the rhythmic processes in STC nuclei. Corticofugal activity modifies oscillation frequency and synchronization strength of the rhythmic activity mainly during tactile stimulation of the vibrissae.

Effects of Spike Anticipation on the Spiking Dynamics of Neural Networks

Synchronization is one of the central phenomena involved in information processing in living systems. It is known that the nervous system requires the coordinated activity of both local and distant neural populations. Such an interplay allows to merge different information modalities in a whole processing supporting high-level mental skills as understanding, memory, abstraction, etc. Though, the biological processes underlying synchronization in the brain are not fully understood there have been reported a variety of mechanisms supporting different types of synchronization both at theoretical and experimental level. One of the more intriguing of these phenomena is the anticipating synchronization, which has been recently reported in a pair of unidirectionally coupled artificial neurons under simple conditions (Pyragiene and Pyragas, 2013), where the slave neuron is able to anticipate in time the behavior of the master one. In this paper, we explore the effect of spike anticipation over the information processing performed by a neural network at functional and structural level. We show that the introduction of intermediary neurons in the network enhances spike anticipation and analyse how these variations in spike anticipation can significantly change the firing regime of the neural network according to its functional and structural properties. In addition we show that the interspike interval (ISI), one of the main features of the neural response associated with the information coding, can be closely related to spike anticipation by each spike, and how synaptic plasticity can be modulated through that relationship. This study has been performed through numerical simulation of a coupled system of Hindmarsh–Rose neurons.

Incomplete metabolism of phytoestrogens by gut microbiota from children under the age of three

Abstract Phytoestrogens are plant-derived polyphenols with structural and functional similarities to mammalian oestrogens. The aim of this work was to study the metabolism of phytoestrogens by children’s intestinal microbiota and to compare it with previous results in adults. Faecal samples of 24 healthy children were subjected to phytoestrogen fermentation assay. Only one child produced equol, while O-desmethylangolensin was found in all. Urolithin production was detected in 14 children and enterolactone in 10. Further comparison with the metabolism of phytoestrogens by adult intestinal microbiota reflected that glycitein, dihydrogenistein, urolithins D and E, enterolactone, secoisolariciresinol and arctigenin were the most important metabolites differentiating between adult and child microbial gut metabolism. Although the child intestinal microbiota showed the ability to metabolise isoflavones, ellagitannins and lignans to a certain extent, it generally showed a reduced metabolism of phytoestrogens, with a lack of 5-hydroxy equol and enterodiol, and less urolithins and enterolactone producers.

Controlling selective stimulations below a spinal cord hemisection using brain recordings with a neural interface system approach

In this work we address the use of realtime cortical recordings for the generation of coherent, reliable and robust motor activity in spinal-lesioned animals through selective intraspinal microstimulation (ISMS). The spinal cord of adult rats was hemisectioned and groups of multielectrodes were implanted in both the central nervous system (CNS) and the spinal cord below the lesion level to establish a neural system interface (NSI). To test the reliability of this new NSI connection, highly repeatable neural responses recorded from the CNS were used as a pattern generator of an open-loop control strategy for selective ISMS of the spinal motoneurons. Our experimental procedure avoided the spontaneous non-controlled and non-repeatable neural activity that could have generated spurious ISMS and the consequent undesired muscle contractions. Combinations of complex CNS patterns generated precisely coordinated, reliable and robust motor actions.