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A Aertsen

Publications and source records attributed to A Aertsen.

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Dynamics of ongoing activity: explanation of the large variability in evoked cortical responses.

Evoked activity in the mammalian cortex and the resulting behavioral responses exhibit a large variability to repeated presentations of the same stimulus. This study examined whether the variability can be attributed to ongoing activity. Ongoing and evoked spatiotemporal activity patterns in the cat visual cortex were measured with real-time optical imaging; local field potentials and discharges of single neurons were recorded simultaneously, by electrophysiological techniques. The evoked activity appeared deterministic, and the variability resulted from the dynamics of ongoing activity, presumably reflecting the instantaneous state of cortical networks. In spite of the large variability, evoked responses in single trials could be predicted by linear summation of the deterministic response and the preceding ongoing activity. Ongoing activity must play an important role in cortical function and cannot be ignored in exploration of cognitive processes.

Animals

Neural dynamics in cortex-striatum co-cultures--II. Spatiotemporal characteristics of neuronal activity.

Neural dynamics in organotypic cortex-striatum co-cultures grown for three to six weeks under conditions of dopamine deficiency are described. Single neuron activities were recorded intra- and extracellularly, and spatiotemporal spreading of population activity was mapped using voltage-sensitive dyes. The temporal properties of spike firing were characterized by interspike interval histograms, autocorrelation and crosscorrelation. Cortical pyramidal neurons (n = 40) showed irregular firing with a weak tendency to burst or to oscillate. Crosscorrelations revealed strong near-coincident firing and synaptic interactions. Disinhibition was a notable feature in a strongly firing cortical interneuron. Cortical activity spread in the co-culture, thus inducing an overall, homogeneous depolarization in the striatal part. Striatal cells were divided into principal cells and type I and II secondary cells. Principal cells (n = 40) were similar to those reported previously in vivo. Spiking activity ranged from irregular spiking at very low rates to episodic bursting, with an average burst duration of 1 s. Interspike intervals were single-peaked. Intracellular recordings revealed characteristic, long-lasting subthreshold depolarizations ("enabled state") that were shortened by local muscarinic receptor blockade. During prolonged time periods in the "enabled state", locally applied bicuculline induced strong firing in most principal neurons. Striatal secondary type I neurons (n = 25) showed high spiking rates, single- and double-peaked interval histograms and low-threshold, short-lasting stereotyped bursting activity and occasional rhythmic bursting. The firing of these neurons was increased by bicuculline. Crosscorrelations showed synchronization of these cells with principal cell activity. Secondary type II neurons (n = 15) revealed tonic, irregular firing patterns similar to cortical neurons, except with occasional firing in doublet spikes. We conclude that under conditions of dopamine deficiency in corticostriatal co-cultures (i) the cortex induces the "enabled" state and typical bursting mode in striatal principal neurons; (ii) principal neurons are strongly inhibited during the "enabled" state; (iii) muscarinic activity, presumably from tonically active striatal cholinergic interneurons, stabilizes the "enabled" state; (iv) striatal GABAergic interneurons receives synaptic inhibition and take part in synchronized activity among striatal principal cells. Our results favor the view of the striatum as a lateral inhibition network.

Animals

Neural dynamics in cortex-striatum co-cultures--I. anatomy and electrophysiology of neuronal cell types.

An in vitro system was established to analyse corticostriatal processing. Cortical and striatal slices taken at postnatal days 0-2 were co-cultured for three to six weeks. The anatomy of the organotypic co-cultures was determined using immunohistochemistry. In the cortex parvalbumin-positive and calbindin-positive cells, which resembled those seen in vivo, had laminar distributions. In the striatum, strongly stained parvalbumin-positive cells resembling striatal GABAergic interneurons and cholinergic interneurons were scattered throughout the tissue. The soma area of these interneuron classes was larger than the average striatal soma area, thus enabling visual selection of cells by class before recording. Cortical neurons with projections to the striatum showed similar morphological features to corticostriatal projection neurons in vivo. No projections from the striatum to the cortex were found. Intracellular recordings were obtained from 94 neurons. These were first classified on the basis of electrophysiological characteristics and the morphologies of cells in each class were reconstructed. Two types of striatal secondary neurons with unique electrophysiological dynamics were identified: GABAergic interneurons (n = 17) and large aspiny, probably cholinergic, interneurons (n = 15). The electrophysiological and morphological characteristics of cortical pyramidal cells (n = 27), cortical interneurons (n = 1), as well as striatal principal neurons (n = 34), were identical to those reported for similar ages in vivo. Organotypic cortex-striatum co-cultures are therefore suitable as an in vitro system in which to analyse corticostriatal processing. The network dynamics, which developed spontaneously in that system, are examined in the companion paper.

Animals

'Dynamics of neuronal interactions' cannot be explained by 'neuronal transients'.

In a recent paper, Vaadia et al. demonstrated that patterns of firing correlation between single neurons in the cortex of behaving monkeys can be modified within a fraction of a second. These changes occur in relation to sensory stimuli and behavioral events, and even without modulations of the neurons' firing rates. These findings call for a revision of prevailing models of neural coding that solely rely on single neuron firing rates. In a defense of these models, Friston put forward an alternative explanation, proposing that the observed correlation dynamics emerge solely from co-modulations of the firing rates of each of the neurons, while the strength of their interaction remains constant. To test this possibility we re-examined the data, adopting Friston's 'neuronal transients' model, and the associated equations and procedures. We found that, to explain the dynamic correlation between a pair of neurons, the alternative interpretation requires that each neuron's response to a single stimulus is composed of a relatively large number of independent components, which co-vary with their counterparts in the companion neuron. This large number of components and their shapes lead us to conclude that, although in principle possible, the neuronal transients model: (i) does not provide a simpler explanation of the experimental results; and (ii) cannot explain these results without itself deviating significantly from most rate code models.

Animals

Dynamics of neuronal interactions in monkey cortex in relation to behavioural events.

It is possible that brain cortical function is mediated by dynamic modulation of coherent firing in groups of neurons. Indeed, a correlation of firing between cortical neurons, seen following sensory stimuli or during motor behaviour, has been described. However, the time course of modifications of correlation in relation to behaviour was not evaluated systematically. Here we show that correlated firing between single neurons, recorded simultaneously in the frontal cortex of monkeys performing a behavioural task, evolves within a fraction of a second, and in systematic relation to behavioural events. Moreover, the dynamic patterns of correlation depend on the distance between neurons, and can emerge even without modulation of the firing rates. These findings support the notion that neurons can associate rapidly into a functional group in order to perform a computational task, at the same time becoming dissociated from concurrently activated competing groups. Thus, they call for a revision of prevailing models of neural coding that rely solely on single neuron firing rates.

Animals

Detecting higher-order interactions among the spiking events in a group of neurons.

We propose a formal framework for the description of interactions among groups of neurons. This framework is not restricted to the common case of pair interactions, but also incorporates higher-order interactions, which cannot be reduced to lower-order ones. We derive quantitative measures to detect the presence of such interactions in experimental data, by statistical analysis of the frequency distribution of higher-order correlations in multiple neuron spike train data. Our first step is to represent a frequency distribution as a Markov field on the minimal graph it induces. We then show the invariance of this graph with regard to changes of state. Clearly, only linear Markov fields can be adequately represented by graphs. Higher-order interdependencies, which are reflected by the energy expansion of the distribution, require more complex graphical schemes, like constellations or assembly diagrams, which we introduce and discuss. The coefficients of the energy expansion not only point to the interactions among neurons but are also a measure of their strength. We investigate the statistical meaning of detected interactions in an information theoretic sense and propose minimum relative entropy approximations as null hypotheses for significance tests. We demonstrate the various steps of our method in the situation of an empirical frequency distribution on six neurons, extracted from data on simultaneous multineuron recordings from the frontal cortex of a behaving monkey and close with a brief outlook on future work.

Action Potentials

Synapses on axon collaterals of pyramidal cells are spaced at random intervals: a Golgi study in the mouse cerebral cortex.

In this study we investigated the arrangement of synapses on local axon collaterals of Golgi-stained pyramidal neurons in the mouse cerebral cortex. As synaptic markers we considered axonal swellings visible at high magnification under the light microscope. Such axonal swellings coincide with synaptic boutons, as has been demonstrated in a number of combined light and electron microscopic studies. These studies also indicated that, in most cases, one bouton corresponds precisely to one synapse. Golgi-impregnated axonal trees of 20 neocortical pyramidal neurons were drawn with a camera lucida. Axonal swellings were marked on the drawings. Most swellings were 'en passant'; occasionally, they were situated at the tip of short, spine-like processes. On axon collaterals, the average interval between swellings was 4.5 microns. On the axonal main stem, the swellings were always less densely packed than on the collaterals. Statistical analysis of the spatial distribution of the swellings did not reveal any special patterns. Instead, the arrangement of swellings on individual collaterals follows a Poisson distribution. Moreover, the same holds to a large extent for the entire collection of pyramidal cell collaterals. This suggests that a single Poisson process, characterized by only one rate parameter (number of synapses per unit length), describes most of the spatial distribution of synapses along pyramidal cell collaterals. These findings do not speak in favour of a pronounced target specificity of pyramidal neurons at the synaptic level. Instead, our results support a probabilistic model of cortical connectivity.

Animals

Current source density profiles of optical recording maps: a new approach to the analysis of spatio-temporal neural activity patterns.

Spatio-temporal spreading of activity in the CA1 region of the rat hippocampal slice was studied by two experimental approaches. At identical locations in the tissue we measured both the extracellular field potential distribution with microelectrode recordings and the intracellular potential distribution by optical recording, using voltage-sensitive fluorescent dyes. Current source density analysis (CSD) was applied to the extracellular field potential distributions (eCSD) to enhance the spatial resolution. In order to obtain an analogous improvement for the optical recordings, we developed a new CSD transformation, which calculates the locations of the transmembrane current generators from the intracellular potential distributions (iCSD). Compared to the underlying fluorescence maps, the new iCSD profiles exhibit a considerable improvement in spatial resolution. Results can be directly interpreted in terms of physiological membrane processes, such as postsynaptic potentials and action potentials. The iCSD profiles show a surprisingly good correspondence with the classical eCSD profiles both qualitatively and quantitatively, the only difference being that cell body activity is reduced in amplitude. Thus, this new optical CSD analysis paves the way for a quantitative interpretation, rather than the hitherto predominantly qualitative interpretation of spatio-temporal activity profiles from optical recording measurements.

Action Potentials

Response synchronization in the visual cortex.

Recently, the classic idea of a 'relational' code in the brain received new impetus from the observation of stimulus-dependent synchronizations in the visual cortex. Work over the past two years has focused on documenting the functional dependencies of such synchronizations. We review and classify the experimental findings with respect to separate spatial and temporal schemes. Thus, we distinguish between different signal classes (spikes, continuous signals), and different types of time-locking to the stimulus. These various classes of synchronization phenomena are discussed with regard to their properties, the underlying mechanisms and their possible relevance for visual processing.

Animals

Rate coherence and event coherence in the visual cortex: a neuronal model of object recognition.

We propose a function-oriented model of the visual cortex. The model addresses an essential task of the visual system: to detect and represent objects. These are defined as sets, which reappear in the input with invariant inner relations. A network, incorporating an idealized description of anatomical and physiological data, is presented with a movie showing various moving objects. In the course of time, as a result of Hebbian plasticity, a connection scheme develops which embodies in its forward and lateral connections the information necessary to perform the operations involved in object recognition. We demonstrate that coherent neural activity can exploit this information. Two types of coherence have to be distinguished in this respect. Rate coherence performs invariance operations and association, while event coherence accomplishes segmentation tasks. The model reproduces and explains experimental findings made both in physiological recordings from the visual cortex and in psychophysical studies.

Animals

Morphological organization of rat hippocampal slice cultures.

Using various histological methods, we investigated the cellular and morphological organization of rat hippocampal slice cultures. Many of the typical features of the hippocampus were retained in vitro over a long period of time. The principal cell types of the hippocampus and dentate gyrus, the pyramidal cells and granule cells, were well preserved and matured in vitro. Nonpyramidal cells and gamma-aminobutyric-acid (GABA) cells were also present in slice cultures and exhibited a strikingly similar dendritic appearance at the light microscopic level. Moreover, GABA-immunoreactive cell bodies and presynaptic terminals could be identified at the electron microscopic level; they expressed typical symmetric synaptic contacts with cell bodies and dendrites. The course of the intrinsic hippocampal fiber pathways--the mossy fibers, Schaffer collaterals, and alveus--was generally retained in vitro. Additional aberrant fiber projections could be identified. Finally, three types of nonneuronal cells could be distinguished on the basis of immunocytochemical methods.

Animals

Neural interactions in the frontal cortex of a behaving monkey: signs of dependence on stimulus context and behavioral state.

In order to gain an understanding of the processes taking place within and between neuronal assemblies, we made simultaneous recordings of spike trains from groups of up to 11 neurons in the frontal cortex of a rhesus monkey, that was trained to perform a sensorimotor behavioral task. We report here on preliminary results from correlation analysis of these neuronal activities, with special emphasis on signs of behaviorally induced modifications of neural interaction, possibly due to rapid modulations of discharge synchronization among the neurons. Our findings suggest that different functional groups of neurons may co-exist within each small volume of cortex, and that neurons may be dynamically recruited into such a group to fulfil a specific function.

Animals

Synaptic plasticity in rat hippocampal slice cultures: local "Hebbian" conjunction of pre- and postsynaptic stimulation leads to distributed synaptic enhancement.

A central theme in neurobiology is the search for the mechanisms underlying learning and memory. Since the seminal work, first of Cajal and later of Hebb, the synapse is thought to be the basic "storing unit." Hebb proposed that information is stored by correlation: synapses between neurons, which are often coactive, are enhanced. Several recent findings suggest that such a mechanism is indeed operative in the central nervous system. Pairing of activity on presynaptic fibers with strong postsynaptic depolarization results in synaptic enhancement. While there is substantial evidence in favor of a postsynaptic locus for detection of the synchronous pre- and postsynaptic event and subsequent initiation of synaptic enhancement, the locus of this enhancement and its ensuing persistence is still disputed: both pre- and postsynaptic contributions have been suggested. In all previous studies, the enhancement was presumed to be specific to the synapses where synchronous pre- and postsynaptic stimulation was applied. We report here that two recording techniques--optical recording, using voltage-sensitive dyes, and double intracellular recordings--reveal that synaptic enhancement is not restricted to the stimulated cell. Although we paired single afferent volleys with intracellular stimulation confined to one postsynaptic cell, we found that strengthening also occurred on synapses between the stimulated presynaptic fibers and neighboring cells. This suggests that synaptic enhancement by the "paired-stimulation paradigm" is not local on the presynaptic axons and that, in fact, the synapses of many neighboring postsynaptic cells are enhanced.

Animals

The neurochrome. An identity preserving representation of activity patterns from neural populations.

Recording of simultaneous but separated activity of neural populations overwhelms the experimenter with a large amount of information. A clearly structured display technique the "Neurochrome" is introduced, usable on-line and real-time. It shows neural activity patterns while preserving neural identity by employing a color code. The Neurochrome assists the experimenter in generating and verifying hypotheses about neural correlations and stimulus-event relations already during the experiment. In auditory research single neurons are characterized by their spectro-temporal sensitivity to auditory stimuli. A straightforward generalization of this concept, applicable to neural populations, is proposed leading to a global indication of a populations' activity to stimuli: the Multi-Unit Spectro-Temporal Sensitivity. This approach is inversely related to the Neurochrome, the latter however containing more information. The combination of both approaches seems quite powerful in the investigation of neural assemblies. The procedures are illustrated with examples of extracellular multiunit recordings from the auditory midbrain of the grassfrog (Rana temporaria L.).

Animals

Statistical and dimensional analysis of the neural representation of the acoustic biotope of the frog.

The field of investigation is the neural representation of acoustic stimuli occurring in the natural environment of the frog. The point of departure is the description of a stimulus ensemble consisting of natural sounds: the acoustic biotope. A relation of statistical and dimensional structure of the acoustic biotope is indicated. The animal used in the neurophysiological experiments is the grass frog, Rana temporaria L.; microelectrode recordings are made in the auditory midbrain. A method is described to determine the existence of a relation between acoustic stimulus and neural events. The form of this relation has been investigated by first- and second-order stimulus-event correlation. While the first one does not give significant results, the second one leads to the spectrotemporal receptive field of the neuron for natural stimuli. Questions are formulated to estimate the value of this receptive field as a functional descriptor of the neuron. Finally, an outline is sketched for a synthetic construction of the bioacoustic space from neuroacoustic subspaces.

Acoustic Stimulation