The analytical characteristics of the dynamics of interneuronal functional connections during conditioned-reflex activity]

The dynamics of functional relations between neurons was studied in the frontal cortex of dogs performing reversal conditioning task. To reveal the functionally relevant relationships between the temporal patterns of correlated firing and behavioral events, we developed an original processing technique. The technique included the following procedures: a) isolation of the "coupled spikes" (CS) from simultaneously recorded impulse trains: b) search for the temporal patterns of correlated firings and their classification by clustering single trials with similar temporal distribution of CS; c) assessment of behavioral significance of the identified patterns by evaluation of the probabilities of coincidence of behavioral events and different CS patterns. Significant correlations between impulse trains were revealed in 38 neuronal pairs of 456 analyzed. The effects of change in behavioral context on the CS dynamics during the task performance were found in 87% of neuronal pairs with correlated activity. In 17 pairs the behavioral conditions were identified, under which potentially connected neurons fired independently during all the periods of the behavioral task. The potentialities of the advanced processing technique are discussed. We suggest that this analysis can provide useful information about the temporal distribution of correlated firings under conditions of nonstereotyped behavior, when an animal reacts in the dynamically organized experimental context.     

The outlook for the experimental study of the network functions of cortical cells during learning]

The main outcome of the experiments described in the paper is an idea on the gnostic cortical microset. Multineuronal activity recorded from the motor cortex of cats with a conditioned response to time and the following cross-correlation analysis revealed a strict distribution of interneuronal connections within the microsystems (between the adjacent neurons) and variable connections between the remote neurons during the active waiting stage of two minute interval. Additional analysis of the narrow (0.5 ms) peaks of the histograms allowed to form a view on the synaptic interaction in time. It was found that there was different temporal distribution of the spikes in the peak obtained due to correlograms of neuronal pairs. Some cortical neurons demonstrated a visible synaptic activation at the end of the waiting period when other signs of the temporary behaviour were absent. Pharmacological testing functional interneuronal connections with acetylcholine and Ca(2+)-suppressing drug EGTA have raised a question on the neurochemical specificity of the intra- and extracortical synapses.     

Temporal organization of interneuronal relations in the cerebral cortex of the cat in relation to the level of alimentary motivation

By means of records of multicellular activity, interneuronal relations and their modifications in two cortical zones (Visual and motor) were studied in cats at different levels of alimentary motivation. For quantitative evaluation of interneuronal relations the statistic method of cross-correlation analysis of impulse trains was used in determining the probability of the appearance of the discharge of one neurone after the impulse of the other one. For groups of neurones in both investigated cortical areas, three-neurones microsystems were singled out and their activity was analyzed by temporal parameters of interaction between neurones at the interval of 120 ms, both within one microarea (intraanalyzer connections) and between microareas of two cortical zones. The correlation of temporal parameters of interneuronal connections (temporal delays in the activity of neuronal pairs) changed depending on spatial localization of neurones and functional condition of the animals. The existence is suggested of "informational" (1-30 ms) and "motivational" (90-120 ms) values of interneuronal relations for interanalyser connections.     

Possible organization pattern of interaction between the generators of cyclic motor activity and inputs from supraspinal and afferent systems

Possible organization patterns of scratching and locomotor generators that allow interpretation of experimentally demonstrated reorganizations in temporal parameters of these generator activities after electrical stimulation of descending and peripheral afferent systems were analyzed with application of mathematical simulation of neuronal generator systems. The results obtained led to the conclusion that patterns of such reorganizations influenced by signals from suprasegmental and/or peripheral systems may be determined by only two factors: 1) the structure of synaptic connections between interneuronal functional groups underlying these generator associations, and 2) the structure of connections between these groups of interneurons and fibers from suprasegmental and peripheral afferent sources. The existence of inhibitory-excitatory actions from descending and afferent systems upon the neurons of locomotor or scratching generator half-centers is a sufficient condition to ensure phasic changes in the sensitivity of these generators to supraspinal and afferent signals. The locomotor generator, unlike the scratching generator, is apparently characterized by a more complex organization of connections between functional neuronal groupings and descending fibers.Translated from Neirofiziologiya, Vol. 25, No. 1, pp. 45–50, January–February, 1993.     

Organization of neocortical neuronal networks

Multiple unit activity in deep layers of the frontal and motor cortices was recorded by chronically implanted semimicroelectrodes in waking cats with different levels of food motivation. From four to seven neuronal spike trains were selected from the recorded multiunit activity. Interactions between neighbouring neurons in the motor and frontal areas of the neocortex (within the local neuronal networks) and between the neurons of these areas (distributed neuronal networks) were estimated by means of statistical crosscorrelation analysis of spike trains within the range of delays from 0 to 100 ms. Neurons in the local networks were divided in two subgroups: the neurons with higher spike amplitudes with the dominance of divergent connections and neurons with lower spike amplitudes with the dominance of convergent connections. Strong monosynaptic connections (discharges with a delay of less than 2 ms) between the neurons with high- and low-amplitude spikes formed the background of the local networks. Connections between low-amplitude neurons in the frontal cortex and high-amplitude neurons in the motor cortex dominated in the distributed networks. A 24-hour food deprivation predominantly altered the late interneuronal crosscorrelations with time delays within the range of 2-100 ms in both local and distributed networks.     

Maximum decoding abilities of temporal patterns and synchronized firings: application to auditory neurons responding to click trains and amplitude modulated white noise

Simultaneous recordings of an increasing number of neurons have recently become available, but few methods have been proposed to handle this activity. Here, we extract and investigate all the possible temporal neural activity patterns based on synchronized firings of neurons recorded on multiple electrodes, or based on bursts of single-electrode activity in cat primary auditory cortex. We apply this to responses to periodic click trains or sinusoïdal amplitude modulated noise by obtaining for each pattern its temporal modulation transfer function. An algorithm that maximizes the mutual information between all patterns and stimuli subsequently leads to the identification of patterns that optimally decode modulation frequency (MF). We show that stimulus information contained in multi-electrode synchronized firing is not redundant with single-electrode firings and leads to improved efficiency of MF decoding. We also show that the combined use of firing rate and temporal codes leads to a better discrimination of the MF.     

Characteristics of the ensemble organization of the human cerebral cortex from birth to 20 years of age

When studying frontal, somatosensory and visual areas of the human cerebral cortex from birth up to 20 years of age in year-to-year intervals, it has been stated that by birth in neocortex all components of the neuron-glio-vascular ensembles are presented. They are not connected in their composition. During the first year of life the size of all types of neurons increases, long-axonal basket neurons differentiate, fasciculi of radial fibers become thick. By 3 years of life in the ensembles the neurons are definitely grouped as clusters. Sizes of spindle-like and satellite neurons increase; they distribute their axonal collaterals vertically, horizontally and in frontal-posterior direction. By 5-6 years of age the horizontal connection system becomes more complex at the expense of longitudinal growth and ramification of lateral and basal dendrites of the pyramidal neurons. In the section transversal areas occupied with cell groups increase. By 9-10 years of age the pyramidal neurons reach their greatest size. By 12-14 years of age the fibrillar component of the cortex increases considerably, inter- and intraensemble horizontal connections become more complex, the system of local connections becomes more plastic owing to development of short-axonal basket-like neurons. By 16-18 years of age the ensemble cortical organization in its main parameters of architectonics reaches the level specific for mature persons.     

A cross-interval spike train analysis: the correlation between spike generation and temporal integration of doublets

A stochastic spike train analysis technique is introduced to reveal the correlation between the firing of the next spike and the temporal integration period of two consecutive spikes (i.e., a doublet). Statistics of spike firing times between neurons are established to obtain the conditional probability of spike firing in relation to the integration period. The existence of a temporal integration period is deduced from the time interval between two consecutive spikes fired in a reference neuron as a precondition to the generation of the next spike in a compared neuron. This analysis can show whether the coupled spike firing in the compared neuron is correlated with the last or the second-to-last spike in the reference neuron. Analysis of simulated and experimentally recorded biological spike trains shows that the effects of excitatory and inhibitory temporal integration are extracted by this method without relying on any subthreshold potential recordings. The analysis also shows that, with temporal integration, a neuron driven by random firing patterns can produce fairly regular firing patterns under appropriate conditions. This regularity in firing can be enhanced by temporal integration of spikes in a chain of polysynaptically connected neurons. The bandpass filtering of spike firings by temporal integration is discussed. The results also reveal that signal transmission delays may be attributed not just to conduction and synaptic delays, but also to the delay time needed for temporal integration. Received: 3 March 1997 / Accepted in revised form: 6 November 1997     

Spike independency in feed-forward networks

A cortical neuron puts thousands of synaptic contacts on other neurons. The effect of the spike event spreads over a large number of neurons. So it is possible for spike timings to be correlated to each other. But there have not been so many reports of spike timing correlations, while there have been many reports of somewhat longer time range correlations through mean spike rates. Can independent firings be preserved in spite of a number of connections? The present study attempts to determine whether independent firings can be propagated through a simple feed-forward neural network. It is assumed that each unit obeys a threshold mechanism at each discrete time and that connections are statistically uniform with the excitation balanced to the inhibition and delay distributed. It is found that the independent firings can be stably propagated through the feed-forward network at a network parameter region, which contains the physiologically reasonable range. Another interesting result is that the independency-stable spike probability has a lower limit 0.0323.     

Functional organization of local neuronal networks in the cat neocortex. Dependence on the food motivation

The multiple unit activity (MUA) from clusters of adjacent neurones in deep layers of the frontal and motor cortex was recorded in alert cats with different levels of alimentary motivation. Up to 7 spike trains were selected from the MUA. Neurones in the local circuits could be divided into 2 groups: large neurones with prevailing divergent characteristics, and small neurones with prevailing convergent characteristics. A 24-hour food deprivation altered the cross-correlation interneuronal connections with a time delay within the range of 2 to 100 ms.     

Dynamic patterns of correlated activity in the prefrontal cortex encode information about social behavior

New technologies make it possible to measure activity from many neurons simultaneously. One approach is to analyze simultaneously recorded neurons individually, then group together neurons which increase their activity during similar behaviors into an “ensemble.” However, this notion of an ensemble ignores the ability of neurons to act collectively and encode and transmit information in ways that are not reflected by their individual activity levels. We used microendoscopic GCaMP imaging to measure prefrontal activity while mice were either alone or engaged in social interaction. We developed an approach that combines a neural network classifier and surrogate (shuffled) datasets to characterize how neurons synergistically transmit information about social behavior. Notably, unlike optimal linear classifiers, a neural network classifier with a single linear hidden layer can discriminate network states which differ solely in patterns of coactivity, and not in the activity levels of individual neurons. Using this approach, we found that surrogate datasets which preserve behaviorally specific patterns of coactivity (correlations) outperform those which preserve behaviorally driven changes in activity levels but not correlated activity. Thus, social behavior elicits increases in correlated activity that are not explained simply by the activity levels of the underlying neurons, and prefrontal neurons act collectively to transmit information about socialization via these correlations. Notably, this ability of correlated activity to enhance the information transmitted by neuronal ensembles is diminished in mice lacking the autism-associated gene Shank3. These results show that synergy is an important concept for the coding of social behavior which can be disrupted in disease states, reveal a specific mechanism underlying this synergy (social behavior increases correlated activity within specific ensembles), and outline methods for studying how neurons within an ensemble can work together to encode information.

Behaviorally-specific patterns of correlated activity between prefrontal neurons normally enhance the information that neuronal ensembles transmit about social behavior. This study shows that in a mouse model of autism, individual neurons continue to encode social information, but this additional information carried by patterns of correlated activity is lost.     

Place representation within hippocampal networks is modified by long-term potentiation

In the brain, information is encoded by the firing patterns of neuronal ensembles and the strength of synaptic connections between individual neurons. We report here that representation of the environment by "place" cells is altered by changing synaptic weights within hippocampal networks. Long-term potentiation (LTP) of intrinsic hippocampal pathways abolished existing place fields, created new place fields, and rearranged the temporal relationship within the affected population. The effect of LTP on neuron discharge was rate and context dependent. The LTP-induced "remapping" occurred without affecting the global firing rate of the network. The findings support the view that learned place representation can be accomplished by LTP-like synaptic plasticity within intrahippocampal networks.     

Neuron classification based on temporal firing patterns by the dynamical analysis with changing time resolution (DCT) method

Spike train data of many neurons can be obtained by multirecording techniques; however, the data make it difficult to estimate the connective structure in a large network. Neuron classification should be helpful in that regard, assuming that multiple neurons having similar connections with other neurons show a similar temporal firing pattern. We propose a novel method for classifying neurons based on temporal firing patterns of spike train data called the dynamical analysis with changing time resolution (DCT) method. The DCT method can evaluate temporal firing patterns by a simple algorithm with few arbitrary factors and automatically classify neurons by similarity of temporal firing patterns. In the DCT method, temporal firing patterns were objectively evaluated by analyzing their dependence on temporal resolution. We confirmed the effectiveness of the DCT method using actual spike train data.     

The interrelations between neurons of the amygdala and hypothalamus during conditioning with selection of food reinforcement quality in cats

Three cats were subjected to appetitive instrumental conditioning to light by the method of the "active choice" of the reinforcement quality. The short-delayed conditioned bar-pressings were reinforced by bread-meat mixture and the delayed response by meat. The animals differed in behavior strategy: two animals preferred bar-pressing with long delay (the so-called "self-control" group) and one animal preferred bar-pressing with short delay (the so-called "impulsive" group). The multiunit activity of the basolateral amygdala and nucleus lateralis of the hypothalamus was recorded through chronically implanted nichrome wire semimicroelecrodes. The interactions between the neighboring neurons in the lateral hypothalamus and basolateral amygdala (within the local neuronal network) and between the neurons of the basolateral amygdala and lateral hypothalamus (distributed neuronal networks in the direction amygdala--hypothalamus and vice versa) were evaluated by means of statistical crosscorrelation analysis of spike trains. The crosscorrelational interneuronal connections in the delay range of 0-100 ms were examined. It was shown that the number of crosscorrelations between the discharges on neurons both in the local networks of basolateral amygdala and distributed networks was significantly higher in "impulsive" cats. In both groups of animals, the percentage of crosscorrelations between neighbouring neurons in the local networks of the lateral hypothalamus was similar. We suggest that the local networks of the basolateral amygdala and amygdalar-hypothalamic distributed neuronal networks are involved in the system of brain structures which determine the individual features of animal behavior.     

Patterns of spatio-temporal correlations in the neural activity of the cat motor cortex during trained forelimb movements

In order to study how neurons in the primary motor cortex (MI) are dynamically linked together during skilled movement, we recorded simultaneously from many cortical neurons in cats trained to perform a reaching and retrieval task using their forelimbs. Analysis of task-related spike activity in the MI of the hemisphere contralateral to the reaching forelimb (in identified forelimb or hindlimb representations) recorded through chronically implanted microwires, was followed by pairwise evaluation of temporally correlated activity in these neurons during task performance using shuffle corrected cross-correlograms. Over many months of recording, a variety of task-related modulations of neural activities were observed in individual efferent zones. Positively correlated activity (mainly narrow peaks at zero or short latencies) was seen during task performance frequently between neurons recorded within the forelimb representation of MI, rarely within the hindlimb area of MI, and never between forelimb and hindlimb areas. Correlated activity was frequently observed between neurons with different patterns of task-related activity or preferential activity during different task elements (reaching, feeding, etc.), and located in efferent zones with dissimilar representation as defined by intracortical microstimulation. The observed synchronization of action potentials among selected but functionally varied groups of MI neurons possibly reflects dynamic recruitment of network connections between efferent zones during skilled movement.     

Ensemble activity of neurons in the visual, frontal, and sensorimotor cortices and dorsal striatum during actualization of behavioral program under conditions of strategy choice

Unit and network activity of neurons in the visual, sensorimotor, and frontal cortical areas and dorsal striatum was investigated in cats under conditions of choice of the reinforcement value depending on its delay. The animals did not differ from each other in behavior. After immediate or delayed responses cats got low- or highly-valuable reinforcement, respectively. Single-unit activity in the visual and sensorimotor cortical areas and dorsal striatum was similar during performance of immediate and delayed responses. However, significant inhibition was observed in the frontal neurons during the delay period. The network activity of visual and frontal cortex displayed smaller number of interneuronal interactions during delayed responses as compared to immediate reactions. The network activity of neurons in the brain structures under study pointed to the interstructural interaction, but only during delayed reactions, steady interneuronal communication was observed between the frontal cortex and dorsal striatum. Thus, both types of estimation of cellular activity revealed differences in the ensemble organization during different types of behavior and showed specific reactions of neuronal ensembles.     

Comparative analysis of the interactions between spontaneous active neurons of the sensomotor cortex of kittens and adult cats

The character of functional interneuronal relations in the sensorimotor cortex during spontaneous neural activity in kitten and adult cats immobilized with d-tubocurarine, was studied by the method of cross-correlations of two impulse series. The data obtained by computation revealed specific age-related interneuronal connections in investigated groups of animals. In kitten aged up to 10 days, the highest percentage of the functional connections was observed which were established mainly due to the influence of a common source. In other groups of animals (kittens of 20, 30 days of postnatal life, adult cats) the common source did not play a significant role in the formation of interneuronal connections. The results showed that inhibitory connections between neurones-are established to the end of the first month of the postnatal life.     

Asynchronous local dynamics contributes to stability of a seagrass bed in Tokyo Bay

It is known that asynchronous temporal variations in local populations can contribute to the stability of metapopulations. However, studies evaluating the hierarchical organization of multiple spatial scales are rare for continuous marine landscapes, especially for marine vegetation such as seagrass beds. In this study, long‐term observation (26 yr) of temporal changes and nested spatial analyses were combined for an extensive seagrass meadow in Tokyo Bay, Japan, using remote sensing and geographic information system technologies. We examined how the dynamics at the whole‐bed scale (~1 km²) are related to those at a local scale (0.04 km²), and investigated the relationship between the seagrass dynamics and long‐term changes in environmental conditions using data on oceanography, water quality, and sediment dynamics. The seagrass bed size fluctuated between a maximum of 1.28 km² (in 1987) and a minimum of 0.39 km² (in 2001), with an average of 0.90 km². The temporal variation in seagrass bed size at the whole‐bed scale correlated with sand movement within the seagrass bed related to changes in the position of a sandbar. Seagrass bed size fluctuated asynchronously at a local scale. Multivariate analyses recognized clusters of local areas showing similar patterns of fluctuation. Temporal patterns in the various clusters responded differently to changes in environmental factors, e.g. the position of the sandbar was highly correlated with seagrass bed size in shallow habitats but not in deeper areas. The magnitudes of the temporal variations for the local clusters were greater than that of the entire bed, suggesting that asynchronous fluctuation in different areas of the bed plays an important role in the overall stability of the seagrass bed. The results of the present study also highlight the importance of physical processes in regulating the temporal dynamics of seagrass beds in shallow sedimentary landscapes.     

Effect of chronic alcoholic intoxication in the rat on the structural organization of the caudate nucleus in their progeny

By means of light (Nissl and Golgi), electron microscopy, as well as using morphometry, structure of neurons and interneuronal connections of the nucleus caudatus has been studied in 21-day-old rats reproduced by chronically alcoholized parents. As demonstrated the investigations, in young rats, physically underdeveloped, there are some signs of a delayed maturation in neurons, dendrites and synapses. Certain distrophic and reparative shifts are observed in all experimental animals. The distrophic changes of neural structures in the nucleus caudatus preponderate over the reparative ones, and in the destructive course not only the neuronal body is involved, but its processes, as well. The lesions of the latter influence organization of the synaptic contacts. This is demonstrated as a sharply decreased number of synapses of the formation studied in the field of vision. The occurring disturbance in the structure of dendrites, which play an important role in the primary integration of the information received by the neuron, can cause development of certain mental disorders in children born in alcoholic families. The reparative changes in neurons and interneuronal connections revealed suppose possible reversibility of the morphological changes observed in the offspring of drunkards.     

Subjective visual perception: from local processing to emergent phenomena of brain activity

The combination of electrophysiological recordings with ambiguous visual stimulation made possible the detection of neurons that represent the content of subjective visual perception and perceptual suppression in multiple cortical and subcortical brain regions. These neuronal populations, commonly referred to as the neural correlates of consciousness, are more likely to be found in the temporal and prefrontal cortices as well as the pulvinar, indicating that the content of perceptual awareness is represented with higher fidelity in higher-order association areas of the cortical and thalamic hierarchy, reflecting the outcome of competitive interactions between conflicting sensory information resolved in earlier stages. However, despite the significant insights into conscious perception gained through monitoring the activities of single neurons and small, local populations, the immense functional complexity of the brain arising from correlations in the activity of its constituent parts suggests that local, microscopic activity could only partially reveal the mechanisms involved in perceptual awareness. Rather, the dynamics of functional connectivity patterns on a mesoscopic and macroscopic level could be critical for conscious perception. Understanding these emergent spatio-temporal patterns could be informative not only for the stability of subjective perception but also for spontaneous perceptual transitions suggested to depend either on the dynamics of antagonistic ensembles or on global intrinsic activity fluctuations that may act upon explicit neural representations of sensory stimuli and induce perceptual reorganization. Here, we review the most recent results from local activity recordings and discuss the potential role of effective, correlated interactions during perceptual awareness.