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Biomedical subjects

M A Nicolelis

Publications and source records attributed to M A Nicolelis.

At least 19 recordsLinked to original sources

Somatotopic maps within the zona incerta relay parallel GABAergic somatosensory pathways to the neocortex, superior colliculus, and brainstem.

Neurons located in the zona incerta (ZI) of the ventral thalamus project to several regions of the central nervous system, including the neocortex, superior colliculus, and brainstem. However, whether these projections are functionally segregated remains unknown. This issue was addressed here by combining neuroanatomical tracers with immunohistochemical staining for gamma-aminobutyric acid (GABA) and/or parvalbumin, coupled with neurophysiological mapping. GABAergic projection neurons were found in four distinct subregions of the ZI including: (1) the rostral pole of the ZI, from which neurons project to the supragranular layers of the neocortex (especially layer I); (2) the dorsal subregion of the ZI, where both ascending projections to the neocortex and descending projections to the pretectal area were observed; (3) the ventral subregion of the ZI, whose neurons project to the superior colliculus; and 3) the caudal pole of the ZI, from which descending projections to the lower brainstem and spinal cord were observed. Somatotopic representations of the contralateral cutaneous periphery were also identified in the dorsal and ventral subregions of ZI, both of which were found to receive dense direct afferent projections from the trigeminal complex, and dorsal column nuclei. These results suggest that the rat ZI is a major somatosensory relay in the ventral thalamus, carrying feed-forward inhibitory signals to neocortical and subcortical targets, in parallel with the excitatory somatosensory pathways.

Afferent Pathways

Neonatal whisker removal in rats stabilizes a transient projection from the auditory thalamus to the primary somatosensory cortex.

A normally transient cross-modal thalamocortical projection from the magnocellular subdivision of the medial geniculate nucleus (MGm) to the primary somatosensory (SI) cortex of rats was found to remain unchanged throughout adulthood following unilateral removal of whiskers in newborn animals. The normal MGm projection to the auditory cortex is not lost in these neonatally whisker-deprived adults rats but some of the MGm neurons send collaterals to both primary auditory and SI cortices. Parallel electrophysiological experiments demonstrated the multimodal character of some MGm neurons, since they responded to both auditory and cutaneous stimulation. These results suggest that the areal distribution in the cortex of thalamocortical projections arising from a multimodal thalamic nucleus, such as the MGm, may be determined during early postnatal development by the normal flow of sensory information from the periphery to the thalamus and that an early postnatal somatosensory deprivation may prevent the normal withdrawal of a cross-modal projection from the MGm to the SI.

Aging

Thalamic plasticity induced by early whisker removal in rats.

Neurophysiological mapping was used to study the effects of early postnatal removal of mystacial whiskers on the organization of cutaneous receptive fields (RFs) within the ventral posterior thalamus (VP) of rats. This sensory deprivation induced an extensive reorganization of the thalamus, as reflected in larger facial or continuous overlapping face-body RFs and a higher proportion of slowly-adapting responses. Mapping of the VP of young rats (2-3 weeks old) demonstrated that the functional organization of the immature VP thalamus resembles that of the sensory-deprived VP, suggesting that an early postnatal sensory deprivation may interfere with the normal process of thalamic development.

Aging

Structural analysis of neural circuits using the theory of directed graphs.

A new approach to analysis of structural properties of biological neural circuits is proposed based on their representation in the form of abstract structures called directed graphs. To exemplify this methodology, structural properties of a biological neural network and randomly wired circuits (RC) were compared. The analyzed biological circuit (BC) represented a sample of 39 neural nuclei which are responsible for the control of the cardiovascular function in higher vertebrates. Initially, direct connections of both circuits were stored in a square matrix format. Then, standard algorithms derived from the theory of directed graphs were applied to analyze the pathways of the circuits according to their length (in number of synapses), degree of connectedness, and structural strength. Thus, the BC was characterized by the presence of short, reciprocal, and unidirectional pathways which presented a high degree of heterogeneity in their strengths. This heterogeneity was mainly due to the existence of a small cluster of reciprocally connected neural nuclei in the circuit that have access, through short pathways, to most of the network. On the other hand, RCs were characterized by the presence of long and mainly reciprocal pathways which showed lower and absolute homogeneous strengths. Through this study the proposed methodology was demonstrated to be a simple and efficient way to store, analyze, and compare basic neuroanatomical information.

Animals

Rhythmic bacterial susceptibility to antibiotics at a large hospital.

The in vitro susceptibility response of Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa to a set of antibiotics was investigated in a survey comprising 19,380 positive cultures over a period of 5 years in a large hospital environment. Four out of the five species (P. aeruginosa being the exception) presented a species-specific, drug-independent, rhythmic variation of their level of susceptibility to several antibiotics over the time of the study. The species-specific rhythmic responses were further characterized by spectral analysis, autocorrelation and cross-correlation functions. Through this analysis it was possible to rank the species according to their main period of oscillation. The longest period of oscillation was detected for S. aureus (38 months). K. pneumoniae and E. coli presented intermediate values (25 and 23 months respectively), and P. mirabilis the shortest period of oscillation (11 months). Species displaying long periods of oscillation tended to present very low levels of susceptibility, while species displaying short periods of oscillation usually presented the highest levels of susceptibility observed. Although some hospital environmental factors, such as drug consumption, were also analyzed, no correlation was found between them and the in vitro bacterial cyclic responses to antibiotics.

Anti-Bacterial Agents

Ontogeny of corticocortical projections of the rat somatosensory cortex.

Rhodamine-coated microspheres (RCMs) were injected into the primary somatosensory cortex (SI) of rats ranging in age from postnatal (PN) day 1 to adulthood. Ipsilateral corticocortical and callosal projections within the SI were identified as early as PN day 1. At the end of the first PN week, ipsilaterally projecting neurons located in sublayer VIb were the first to assume an adult-like pattern of connectivity. Injections at subsequent postnatal ages revealed that an adult pattern of lamination of ipsilateral corticocortical projections within the SI is established between PN weeks 2 and 3, comprising projection neurons from layers II/III, layer V, and sublayer VIb. Therefore, local interactions in the rat SI are mediated not only by pyramidal neurons of layers III and V, derived from the cortical plate, but also by a subpopulation of ontogenetically older neurons located in the sublayer VIb, which may correspond to the subplate neurons of other species. Overall, these results suggest the existence of three independent short-range corticocortical systems of projections within the rat SI, which differ in terms of the laminar distribution and ontogenetic origin of their cells.

Aging

A major direct GABAergic pathway from zona incerta to neocortex.

Retrograde fluorescent tracers were used to demonstrate a previously unknown but sizable direct gamma-aminobutyric acid (GABA)-containing neuronal pathway from the zona incerta to the neocortex in rats. This incertocortical pathway was found to project bilaterally to the entire neocortex and exhibited a rough corticotopic organization. Many of the zona incerta neurons projecting to the parietal and occipital cortices could also be immunohistochemically stained with antibodies to glutamic acid decarboxylase and GABA. Few of these neurons were immunoreactive to tyrosine hydroxylase antibodies, which identify dopamine-containing neurons. Injections in the frontal and entorhinal cortices labeled many neurons near or within the dopaminergic A13 subdivision of the zona incerta. In addition, the incertocortical system was found to be significantly larger during early postnatal (2 to 3 weeks) development. The projection pattern of this newly discovered pathway resembles that of the monoaminergic and cholinergic systems, arising from the brainstem and forebrain, suggesting possible similarities of function.

Animals

Connection, a microcomputer program for storing and analyzing structural properties of neural circuits.

The application of a microcomputer-based system (the Connection system) designed to deal with neuroanatomical information commonly analyzed by researchers and involved in the study of structural properties of neural circuits is presented. This system can be employed at first as a readily-accessible database containing physiological and anatomical data from nuclei of the central nervous system which define a network with up to 45 elements and their subdivisions and connections. Once the database from a specific network is built and stored in a file, routines of this system can be used to classify the nuclei in term of their afferents and efferents and also to display all possible pathways linking any pair of nuclei and their respective length (number of synapses). The role of such a system as an auxiliary tool in neuroanatomical and electrophysiological research is discussed by presenting the results obtained from the analysis of the neural circuits involved in cardiovascular function control in higher vertebrates.

Algorithms

Structural characterization of the neural circuit responsible for control of cardiovascular functions in higher vertebrates.

A comparison of structural properties of a biological neural system responsible for cardiovascular function control in higher vertebrates with randomly connected networks was pursued using matrix representations of those circuits. The biological circuit was characterized by the presence of some heavily connected nuclei in contrast to the random networks that had equally distributed connections between their elements. This property of the analysed biological circuit was shown to account for a high logarithmic correlation found between two indexes defined to represent pointwise features of the nuclei and their global contribution to the whole network. The first index is obtained by the product of the number of inputs and of outputs of a nucleus and was called power index (PI). The second one, called occurrence index (OI), defines how many times a specific nucleus is crossed when all possible pathways joining two nuclei of the circuit are obtained. This PI-OI correlation was clearly dependent on the pathway length distribution (expressed in number of synapses), and was maximal considering pathways with a low number of synapses. When randomly connected circuits were analysed lower correlation was found between the same two indexes and only for much longer pathways. Therefore, it is proposed that the analysis of the PI-OI correlation can be useful to quantify structural differences between biological neural circuits as distinguished from randomly connected networks and also between neural systems at different levels of phylogenetic and ontogenetic development.

Animals

Collagen fibril diameters in arteries of mice. A comparison of manual and computer-aided morphometric analyses.

Arteries of mice were studied by a silver impregnation technique, by the Picrosirius-polarization method and by transmission electron microscopy. The histochemical results obtained coincided with the electron-microscopic observations in showing the presence of two distinct collagen populations, segregated into different compartments of each artery. The fibrous component of the tunica media was comprised of reticulin fibers, which displayed a distinct argyrophilia when studied by means of the silver impregnation technique, and showed up as thin, weakly birefringent, greenish fibers when examined with the aid of the Picrosirius-polarization method. In addition, the electron-microscopic studies disclosed the presence of thin collagen fibrils in the tunica media, contrasting with the thicker fibrils that could be localized ultrastructurally to the tunica adventitia where nonargyrophil, coarse collagen fibers had been characterized by the histochemical methods used. In this respect, collagen distribution in arteries of mice is very similar to the pattern that was consistently observed in the other species studied, which argues in favor of the existence of a uniform structural pattern of collagen distribution that is a general phenomenon in vertebrate arteries. Experimental results comparing the traditional method and the computer-aided measurement of collagen fibril diameters showed that the system provides results equivalent to those produced by manual execution. In addition, the advantage in speed of the computer-aided method should prove useful in complicated studies where numerous structures are involved.

Animals

Time series analysis of rhythmic bacterial resistance development to antibiotics.

The sensitivity data of Staphylococcus aureus and Escherichia coli to a large set of antibiotics have undergone time series procedures of analysis in order to highlight possibly periodical behavior in time. These oscillational patterns have been characterized through the use of FFT and cross-correlational and variance analysis and were proved to be species-specific and drug-independent. S. aureus was shown to have a large period of oscillation (40 months) when compared to E. coli (from 7 to 11 months). A perfect species distinction was only possible through cross correlation. These results may reflect the influence of the local environment, since this finding was not referred to in the literature.

Analysis of Variance

A mathematical model for spirometry.

A model originally designed to fit population growth data was investigated to determine whether it could fit spirometric traces as a function of time in normal and ill humans and in normal rats, obtained, respectively, by spirometer and whole-body plethysmography. The model showed great accuracy when applied to a simple spirometer coupled with an analog-to-digital converter interfaced with a personal computer. It also proved to be a good alternative for the more expensive and less accurate electronic devices, as derivative systems, and may be an attractive method for research and/or diagnostic centers.

Animals

Mathematical model of Klebsiella pneumoniae resistance to amikacin and gentamicin.

1. The resistance of Klebsiella pneumoniae to amikacin and gentamicin was studied by a mathematical model to predict the rate of sensitivity decrease. The results accurately matched experimental data, showing that the model is a reliable predicting tool. 2. The observations were carried out over six years and included 2677 cultures that were positive for K. pneumoniae. At the beginning of the observation period, 85.7% of the cultures were sensitive to amikacin and 40.8% were sensitive to gentamicin. Sensitivity to amikacin showed a surprisingly rapid decrease; at the end of the experimental period, amikacin and gentamicin sensitivities were 33.3% and 27.8%, respectively. 3. We conclude that patterns of resistance of other bacteria could be investigated using this method.

Amikacin

Pulmonary function of rats exposed to ethanol and gasoline fumes.

This paper describes the effects of repeated exposure to gasoline and ethanol exhaust fumes on the pulmonary mechanics of rats assessed by whole-body plethysmography. Two groups of 12 male Wistar albino rats each were tested before and after exposure to diluted gasoline or ethanol exhaust gases for 5 weeks, 8 h per day and 5 days per week. An additional group of 12 rats were exposed to clean air under the same experimental conditions. The variations of the functional parameters observed in the three groups before and after exposure were compared. Peak Expiratory Flow and Forced Expiratory Mean Flows in the ranges 0-25%, 25-50% and 50-75% of Forced Vital Capacity were significantly reduced in animals exposed to gasoline exhaust fumes, whereas the group exposed to ethanol exhaust fumes did not differ from the control group. This respiratory impairment is probably due to the presence of SO2 and the quality of the hydrocarbons in gasoline exhaust gases.

Animals

Application of a microcomputer-based system in the analysis of infection data at the emergency units of a large hospital.

After three years of retrospective study in four emergency units from a large hospital (2000 beds) and analysis of 6283 positive cultures, a microcomputer database system was built to store information concerning nosocomial infections in order to help the clinical staff from those units to study the incidence of 20 bacterial species and their sensitivity pattern evolutions for 27 antibiotics (from samples in 15 different collecting sites). This system was developed as an alternative to the hospital mainframe computer microbiological reports. It put emphasis on graphical outputs instead of the coded tables generated by the bigger system. This orientation and the possibility of sectorial infection data analysis were responsible for the general acceptance of the microcomputer-based system by the clinical staff. As the first practical results, the system was able to detect a particular increase in the incidence of Staphylococcus aureus in surgical emergency units (up to 21.6% in 1982) as well as the dissemination of the antimicrobial resistance patterns of S. aureus and Klebsiella pneumoniae from the surgical units to the clinical ones. The time evolution behaviour of Pseudomonas aeruginosa, Escherichia coli and other nonfermentative Gram negative bacilli was also studied to complete the analysis of the most pathogenic bacterial species found in our emergency units.

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