Biomedical subjects

A E Villa

Publications and source records attributed to A E Villa.

At least 19 recordsLinked to original sources

PubMed2001

Different tonic regulation of neuronal activity in the rat dorsal raphe and medial prefrontal cortex via 5-HT(1A) receptors.

It has been established that 5-HT(1A) receptors are expressed both presynaptically as autoreceptors by 5-HT containing neurones, and postsynaptically by a variety of other neurones. Activation of either somatodendritic 5-HT(1A) autoreceptors or postsynaptic 5-HT(1A) receptors induces hyperpolarisation and inhibition of action potential discharge of the neurones, but it is unclear whether 5-HT(1A) receptors are under a general tonic influence by 5-HT. In the present study, using single unit recordings from both anesthetized and non-anesthetized rats, we show that the activity of neurones in the medial prefrontal cortex is not altered by systemic administration of the selective 5-HT(1A) receptor antagonist, WAY 100635. In contrast, WAY 100635 increased the firing rate of 5-HT neurones in the dorsal raphe nucleus. Our findings indicate a tonic activation of presynaptic somatodendritic but not postsynaptic cortical 5-HT(1A) receptors.

Animals↗

PubMed2001

A pattern grouping algorithm for analysis of spatiotemporal patterns in neuronal spike trains. 1. Detection of repeated patterns.

The existence of precise temporal relations in sequences of spike intervals, referred to as 'spatiotemporal patterns', is suggested by brain theories that emphasize the role of temporal coding. Specific analytical methods able to assess the significance of such patterned activity are extremely important to establish its function for information processing in the brain. This study proposes a new method called 'pattern grouping algorithm' (PGA), designed to identify and evaluate the statistical significance of patterns which differ from each other by a defined and small jitter in spike timing of the order of few ms. The algorithm performs a pre-selection of template patterns with a fast computational approach, optimizes the jitter for each spike in the template and evaluates the statistical significance of the pattern group using three complementary statistical approaches. Simulated data sets characterized by various types of known non stationarities are used for validation of PGA and for comparison of its performance to other methods. Applications of PGA to experimental data sets of simultaneously recorded spike trains are described in a companion paper (Tetko IV, Villa AEP. A pattern grouping algorithm for analysis of spatiotemporal patterns in neuronal spike trains. 2. Application to simultaneous single unit recordings. J Neurosci Method 2000; accompanying article).

Action Potentials↗

PubMed2001

A pattern grouping algorithm for analysis of spatiotemporal patterns in neuronal spike trains. 2. Application to simultaneous single unit recordings.

This study demonstrates the practical application of the pattern grouping algorithm (PGA), presented in the companion paper (Tetko IV, Villa AEP. A pattern grouping algorithm for analysis of spatiotemporal patterns in neuronal spike trains. 1. Detection of repeated patterns. J. Neurosci. Methods 2000; accompanying article), to data sets including up to 30 simultaneously recorded spike trains. The analysis of a large network of simulated neurons shows that the incidence of patterns cannot be simply related to an increase in firing rates obtained after Hebbian learning. Patterns that disappeared and reappeared in the thalamus of anesthetized rats when the cerebral cortex was reversibly inactivated suggest that widespread cell assemblies contribute to the generation and propagation of precisely timed activity. In an another experiment multiple spike trains were recorded from the temporal cortex of freely moving rats performing a complex two-choice discrimination task. The presence or absence of particular patterns in the period preceding the cue was associated with changes in reaction time. In conclusion, neuronal network interactions may generate spatiotemporal firing patterns detectable by PGA. We provide evidence of such patterned activity associated with specific animal's behavior, thus suggesting the existence of complex temporal coding schemes in the higher nervous centers of the brain.

Action Potentials↗

PubMed2000

[Neuroheuristics, a new paradigm in neuroscience].

The recent advances of Molecular Biology and Computer Sciences in Neurosciences open unprecedented perspectives for biomedical investigation. Neuroheuristics offers as a new paradigm where these disciplines are no longer restricted to their technical expertise, but rather subserve a dynamical approach to the clinical and fundamental research for the neurological sciences.

Animals↗

PubMed1999

c-Fos expression in the auditory pathways related to the significance of acoustic signals in rats performing a sensory-motor task.

Neuronal activity was established in the auditory pathways in relation to behavioural response and cognitive information processing during a sensory-motor acoustic learning. Rats were trained in three consecutive phases. The first phase was an association between an auditory stimulus and a food reward; the second phase a simple discrimination between two sounds of different frequency components, and the third phase a more complex discrimination involving both spectral and spatial sound dimensions. Auditory stimuli were bursts of complex sounds lasting 500 ms. Neuronal activity related to the behaviourally relevant stimuli was established in 20 "learning" rats undergoing this protocol, which were progressively sacrificed at the beginning, middle and end of each phase. For comparison, activity was also established in four "control" rats exposed to the same stimuli delivered pseudo-randomly, thus carrying no behavioural meaning. Neuronal activity was assessed immunocytochemically using the functional marker Fos. To establish a baseline, two rats were unexposed to controlled acoustic stimulation ("unstimulated" rats). In the superior olivary complex (SOC), inferior colliculus (IC) and medial geniculate body (MGB), the number of Fos-like immunopositive cells was comparable in "learning" and "control" animals, but higher than in the "unstimulated" rats. In the auditory cortex (AC), most prominently in the secondary area Te2, the number of Fos-like positive cells differed between "learning" and "control" rats, suggesting that the auditory cortical areas may be involved in the encoding of the behavioural significance of the acoustic stimuli.

Acoustic Stimulation↗

PubMed1999

Pharmaceutical fingerprinting in phase space. 1. Construction of phase fingerprints.

The present study proposes a general method for constructing pharmaceutical fingerprints in the analysis of HPLC trace organic impurity patterns. The approach considers signals in phase space and accounts for two different types of noise: additive and perturbative. The first type, additive noise, contributes to distortion of the absolute values of signal peaks. The second type, perturbative noise, contributes to variations of the retention times of signal peaks and distorts the time scale of the trace organic impurity patterns. The ability of the proposed approach to consider both types of noise significantly distinguishes it from existing methods of data analysis that are usually designed to treat only the additive noise. Analysis of the HPLC signals in phase space eliminates the problem of perturbation noise and enables detection and comparison of similar signal segments recorded at different retention times. The current study analyzes the chromatographic trace organic impurity patterns collected from six different manufacturers of L-tryptophan using three HPLC columns. For five manufacturers the variability of data recorded with the same column are in perfect agreement with the proposed model. A significant variance of parameters is detected for one manufacturer, thus indicating a possible change in its product consistency. The analysis in phase space is also used to explain the previously detected variability of HPLC signals across columns. The accompanying paper reports an application of the proposed approach for the pattern recognition of HPLC data.

Algorithms↗

PubMed1999

Pharmaceutical fingerprinting in phase space. 2. Pattern recognition.

The current study introduces an approach for pattern recognition of drug manufacturers according to their HPLC trace impurity data. This method considers signals in phase space and accounts for two different types of noise: additive and perturbative. The pharmaceutical fingerprints are estimated as mean trajectories of HPLC trace impurity data and are used as reference models for recognition of new data by the minimal length classifier. The chromatographic trace organic impurity patterns collected from six different manufacturers of L-tryptophan are analyzed as an example. The prediction ability of the new method tested using three different cross-validation procedures remains about 95% even if the number of available data in the training sets decreases by 5 times. The accuracy of prediction in phase space is superior compared to results calculated using a Window Preprocessing method and artificial neural networks. The difference in performance between new and previous methods becomes more significant under particular conditions that are more adequate for practical application of the method. In addition, the current approach enables simple and comprehensive interpretation of the calculated results.

Artificial Intelligence↗

PubMed1999

Spatiotemporal activity patterns of rat cortical neurons predict responses in a conditioned task.

Precise and repeated spike-train timings within and across neurons define spatiotemporal patterns of activity. Although the existence of these patterns in the brain is well established in several species, there has been no direct evidence of their influence on behavioral output. To address this question, up to 15 neurons were recorded simultaneously in the auditory cortex of freely moving rats while animals waited for acoustic cues in a Go/NoGo task. A total of 235 significant patterns were detected during this interval from an analysis of 13 hr of recording involving over 1 million spikes. Of particular interest were 129 (55%) patterns that were significantly associated with the type of response the animal made later, independent of whether the response was that prompted by the cue because the response occurred later and the cue was chosen randomly. Of these behavior-predicting patterns, half (59/129) were associated with an enhanced tendency to go in response to the stimulus, and for 11 patterns of this subset, trials including the pattern were followed by significantly faster reaction time than those lacking the pattern. The remaining behavior-predicting patterns were associated with an enhanced NoGo tendency. Overall mean discharge rates did not vary across trials. Hence, these data demonstrate that particular spatiotemporal patterns predict future behavioral responses. Such presignal activity could form templates for extracting specific sensory information, motor programs prespecifying preference for a particular act, and/or some intermediate, associative brain process.

Acoustic Stimulation↗

PubMed1999

Preferential induction of fos-like immunoreactivity in granule cells of the cochlear nucleus by acoustic stimulation in behaving rats.

Neuronal activity in the cochlear nucleus was mapped in relation to acoustic stimuli that signalled a sensory-motor response, using Fos-like immunoreactivity. Rats were trained to associate an acoustic stimulus with a reward and then to discriminate between two sounds ('learning' rats; n = 18). The same stimuli carrying no behavioural significance were pseudo-randomly presented to 'control' rats (n = 4) to differentiate stimulus related- from learning related-activity. To establish a baseline, Fos-like immunoreactivity was determined in rats (n = 2) unexposed to acoustic stimulation. The number of Fos-positive cells was significantly increased in the rats exposed to sounds ('learning' and 'control') as compared to the non-stimulated animals. This stimulus related increase of Fos-like activity in the cochlear nucleus was most prominent in a subpopulation of small neurons, whose spatial distribution corresponds to that of the granule cells. There was also an increase in the number of Fos-positive neurons of larger size, but less prominent than for the small cells. Brief exposure to sounds (30 s) was sufficient to induce Fos-like activity.

Acoustic Stimulation↗

PubMed1999

Corticofugal modulation of functional connectivity within the auditory thalamus of rat, guinea pig and cat revealed by cooling deactivation.

Microelectrode recordings were simultaneously performed at multiple sites in the medial geniculate body (MGB) of anesthetized cats, rats and guinea pigs. We studied the effect of cortical deactivation on the association of neural activity within the thalamus during spontaneous activity. The corticofugal influence was suppressed by temporary cooling of the auditory cortex. Pairs of spike trains recorded from the same electrode were distinguished from cases where units were in MGB but recorded with different electrodes. Time domain analyses included crosscorrelations and search for precise repetition of complex spatiotemporal firing patterns of reverberating thalamic circuits. As a complementary approach we performed bispectral analyses of simultaneously recorded local field potentials in order to uncover the frequency components of their power spectra which are non linearly coupled. All results suggest that new functional neuronal circuits might appear at the thalamic level in the absence of input from the cortex. The newly active intrathalamic connections would provide the necessary input to sustain the reverberating activity of thalamic cell assemblies and generate low frequency non-linear interactions. The dynamic control exerted by the cortex over the functional segregation of information processing carried out in the thalamus conforms with theoretical neural network studies and with the functional selectivity-adaptive filtering theory of thalamic neuronal assemblies. Although this general conclusion remains valid across species, specific differences are discussed in the frame of known differences of the microcircuitry elements.

Animals↗

PubMed1999

Prediction of partition coefficient based on atom-type electrotopological state indices.

The aim of this study was to determine the efficacy of atom-type electrotopological state indices for estimation of the octanol-water partition coefficient (log P) values in a set of 345 drug compounds or related complex chemical structures. Multilinear regression analysis and artificial neural networks were used to construct models based on molecular weights and atom-type electrotopological state indices. Both multilinear regression and artificial neural networks provide reliable log P estimations. For the same set of parameters, application of neural networks provided better prediction ability for training and test sets. The present study indicates that atom-type electrotopological state indices offer valuable parameters for fast evaluation of octanol-water partition coefficients that can be applied to screen large databases of chemical compounds, such as combinatorial libraries.

Chemical Phenomena↗

PubMed1999

Estimation of the fraction of an ingested dose of fluoride excreted through urine in pre-school children.

OBJECTIVE: To determine the fraction of an ingested fluoride dose of 1 mg in 50 mL orange juice that is excreted through the urine (FUEF) of children aged 3-5 years. METHODS: Eighty-eight controlled determinations involving 24-hour urinary collections from a total of 48 children were carried out during consecutive control and test days. Net fluoride urinary excretion due to the ingested dose was calculated as the difference between the total amount of fluoride excreted by each child on test and control days. RESULTS: Excretion of the fluoride ingested from the single fluoride dose presented an average value of 30.7% (95% CI: 28.9-32.5%). No significant associations were found between individual FUEF values with either anthropometrical variables or urinary pH values. The average FUEF value found in the present study lies between previously reported values for infants and young adults. The epidemiological usefulness of the FUEF values in estimating daily fluoride dose in pre-school children is discussed.

Administration, Oral↗

PubMed1998

Computer assisted neurophysiology by a distributed Java program.

We have developed a distributed software package which allows neurophysiologists to have at hand a set of network and graphic tools in order to perform the analysis of data collected from the electrical activity of neurons, studied in the experimental laboratory. This system is built around three major components. First, the experimental data are processed in order to select specific data files from the networked computer and display the spike trains as raster dots. The second part selects one type of analysis (e.g., cross-correlation, out of a set of possible choices) after configuration of some specific parameters. Finally, the third component deals with the results of data analyses, which are selected and displayed on a multi-parameter graphic "ring binder." We have used the Java programming language to implement this application. This recent object-oriented language offers platform-independent software tools including graphic package and standard network protocols.

Algorithms↗

PubMed1998

Discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus of the rat.

The aim of the present study was to characterize the discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the rat. In the absence of acoustic stimulation, two types of spontaneous discharge patterns were observed: units tended to fire in a bursting or in a nonbursting mode. The distribution of units in the DNLL based on spontaneous firing rate followed a rostrocaudal gradient: units with high spontaneous rates were most commonly located in the rostral part of the DNLL, whereas in the caudal part units had lower spontaneous discharge rates. The most common response pattern of DNLL units to 200 ms binaural noise bursts contained a prominent onset response followed by a lower but steady-state response and an inhibitory response in the early-off period. Thresholds of response to noise bursts were on average higher for DNLL units than for units recorded in the inferior colliculus under the same experimental conditions. The DNLL units were arranged according to a mediolateral sensitivity gradient with the lowest threshold units in the most lateral part of the nucleus. In the rat, as in other mammals, the most common DNLL binaural input type was an excitatory response to contralateral ear stimulation and inhibitory response to ipsilateral ear stimulation (EI type). Pure tone bursts were in general a more effective stimulus compared to noise bursts. Best frequency (BF) was established for 97 DNLL units and plotted according to their spatial location. The DNLL exhibits a loose tonotopic organization, where there is a concentric pattern with high BF units located in the most dorsal and ventral parts of the DNLL and lower BF units in the middle part of the nucleus.

Acoustic Stimulation↗

PubMed1998

Estimation of optimal concentration of fluoride in drinking water under conditions prevailing in Chile.

The purpose of this comparative study of caries and dental fluorosis experience in Chilean children was to estimate the optimal range of fluoride concentration in tap water under conditions currently prevailing in Chile. The sample included 2431 schoolchildren 7, 12 and 15 years old, life-long residents of five communities with fluoride concentrations in their tap water in the range 0.07-1.1 mg/L. The study population received an oral clinical examination including caries experience and an enamel fluorosis evaluation of the permanent dentition (Dean's scoring system). For 15-year-old children, the DMFT index changed from 5.06 to 2.60, and for 12-year-olds it changed from 3.10 to 1.36 when fluoride water concentration changed from 0.07 to 1.10 mg/L. For 7-year-old children the dmft index correspondingly changed from 3.67 to 1.59. The relationship between DMFT for 12-year-olds and water fluoride concentration was best fitted by a logarithmic function (r2=0.98). The Community Fluorosis Index (CFI) was used to assess enamel fluorosis in the study population, and it showed a linear relationship (r2=0.983) with increasing fluoride concentration of water for the 12-year-old group. Results obtained suggest that under current Chilean conditions, the optimal range of fluoride concentration in potable water should lie in the 0.5-0.6 mg/L range.

Adolescent↗

PubMed1998

Dental fluorosis in Chilean children: evaluation of risk factors.

The purpose of this case-control study was to determine the association between very-mild-to-moderate enamel fluorosis and exposure during early childhood to fluoridated water, mainly through ingestion of powdered milk. Analysis was performed on 136 residents of the optimally fluoridated community of San Felipe in the Chilean Fifth Region, who were categorised into one of three groups according to their age when water fluoridation was introduced in 1986: Group I was born after 1986; Group II was 16-24 months old in 1986; and Group III was >24 months of age. The case and control subjects were selected on the basis of a clinical examination given in July 1996. Dean's scoring system was used to determine fluorosis status. Risk factor exposure was ascertained by a questionnaire used in interviews with mothers of participating children. Logistic regression analysis, after adjustment for confounding variables, revealed that very-mild-to-moderate enamel fluorosis of permanent central maxillary incisors (CMI) was strongly associated both with the age of the subjects when water fluoridation began and with breast-feeding duration for children belonging to Group I. Subjects in Group I were 20.44 times more likely (95% CI: 5.00-93.48) to develop CMI fluorosis than children who were older than 24 months (Group III) when fluoridation began. Subjects who were between 16 and 24 months old when water fluoridation began were 4.15 times more likely (95% CI: 1.05-16.43) to have CMI fluorosis than children older than 24 months. An inverse association was found with breastfeeding duration (OR=0.86, 95% CI: 0.75-0.98) among Group I subjects but not in Groups II and III. Results obtained suggest that the current fluoride concentration in drinking water may be contributing to fluorosis. Further studies will be necessary to determine the relative competing risks of dental fluorosis and dental caries in Chilean children in order to establish the most appropriate water fluoridation level in Chile.

Analysis of Variance↗

PubMed1997

Ketamine modulation of the temporal pattern of discharges and spike train interactions in the rat substantia nigra pars reticulata.

This study compares the temporal pattern of discharges of extracellularly recorded substantia nigra pars reticulata (SNr) single units in two experimental conditions: Equithesin- and ketamine-induced anesthesia. The analysis of the statistical properties of the spike trains recorded in the Equithesin group of animals showed that this experimental condition could be considered as a control condition with respect to previous data reported in the literature. We investigated the glutamatergic modulation of SNr activity at spike train level in a steady-state condition by using the anesthetic agent ketamine, which is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) glutamatergic receptors. The most relevant effect of ketamine at single unit level was to induce burst discharges, with an intraburst frequency rate near 50 Hz, specifically in units characterized by an initial long refractoriness in the Equithesin condition. The other classes of single units tended to discharge at a higher rate without any significant change in their temporal pattern of firing. Simultaneous recording of the spike trains of 108 SNr pairs (46 and 62 during Equithesin and ketamine condition, respectively) were equally distributed between pairs of units simultaneously recorded from the same electrode and from distinct electrodes at a distance up to 400 microm in the same hemisphere. Ketamine induced a significant increase in the number of pairs with synchronous firing (from 4 to 49%), which was strongly, but not exclusively, associated with an increased tendency to fire in bursts. Neighboring cells tended to fire with a similar pattern in either condition of recording, whereas synchronous firing between distant cells was observed only during ketamine condition.

Action Potentials↗

PubMed1996

Low-dimensional chaotic attractors in the rat brain.

The existence of chaotic attractors for discrete time series, derived from the occurrences of spikes during electrophysiological recordings, was investigated. The time series included between 800 and 5200 points per analyzed record. The spike trains were recorded in the substantia nigra pars reticulata (n = 13) and in the auditory thalamus (n = 14). The experiments were performed on anesthetized rats during spontaneous activity and during auditory stimulation. According to standard methods of dynamical systems theory, an embedding space was constructed using delay coordinates. The embedding and correlation dimensions were computed by means of the correlation integrals. For 7 of 27 samples, a deterministic structure with a low embedding dimension (ranging between 2 and 6) and a correlation dimension between 0.14 and 3.3 could be determined. Evidence was found that the sensory stimulation may affect the chaotic behavior. Single units recorded simultaneously from the same electrode tip may display different chaotic dynamics, even with a similar time-locked response to the stimulus onset.

Acoustic Stimulation↗