The individual organization of frontal-hippocampal networks during realization of different behavioral tasks

Four cats were subjected to appetitive instrumental conditioning with light as a conditioned stimulus by the method of "active choice" of the reinforcement quality: short-delay conditioned bar-press responses were followed by bread-meat mixture and the delayed responses--by meat. The animals differed in behavior strategy: four animals preferred bar-pressing with long delay (so called "self-control" group); two animal preferred bar-pressing with short-delay (so called "impulsive" group). Then all the animals were learned to short-delay (1 s) instrumental conditioned reflex to light (CS+) reinforced by meat. The multiunit activity in the frontal cortex and the hippocampus (CA3) was recorded through chronically implanted nichrome-wire semimicroelectrodes. The interactions among the neighboring neurons in the frontal cortex and hippocampus (within the local neuronal networks) and between the neurons of the frontal cortex and hippocampus (distributed neuronal networks of frontal-hippocampal and hippocampal-frontal directions) were evaluated by means of statistical crosscorrelation analysis of the spike trains. Crosscorrelation interneuronal connections in the delay range 0-100 ms were explored. It was shown that the functional organization of the frontal and hippocampal neuronal networks differed in choice behavior and was similar during realization of short-delayed conditioned reflex. We suggest that the local and distributed neural networks of the frontal cortex and hippocampus take part in the realization of cognitive behavior, in particularly in the processes of the decision making.     

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.     

Interrelations between neurons of the frontal cortex and hippocampus under cholinergic deficit in choice behavior of cats

Appetitive instrumental conditioned reflexes on light (CS+) were formed in six cats by the method of "active choice" of quality of reinforcement; bread-meat mixture was given after short-delay conditioned bar-press responses, and the delayed responses were rewarded by meat. The animals differed in choice behavior strategy: "self-control", "ambivalent", "impulsive". The multiunit activity in the frontal cortex and hippocampus (CA3) was recorded. Cross-correlation analysis was used for estimation of correlation of activities in neuronal pairs in the frontal cortex and hippocampus (distributed frontal-hippocampal networks) and pairs within the same structure (frontal and hippocampal local neuronal networks). It was shown that the number of cross-correlations between the discharges of neurons both in the local and distributed networks was significantly higher in "self-control" cats. Under conditions of systemic administration of antagonists of muscarinic central cholinoreceptors (trihexyphenidyl and scopolamine), the bar-press conditioning impaired, the number of direct interneuronal connections decreased, and the number of externally synchronized correlations ("common input") significantly increased. The results suggest that the local and distributed neural networks of the frontal cortex and hippocampus are involved in the system of brain structures that determine the behavioral strategy of "self control".     

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.     

Cooperative neuronal activity of the n. accumbens and the frontal cortex in cats trained to choose stimuli of various value

It was shown that the two-way interaction between neurons of the frontal cortex and n. accumbens progressively increases, whereas their regularity simultaneously decreases with the rise in impulsiveness and drop in self-control in behavior. In case of the long-latency instrumental reactions, a control of the frontal cortex neurons by neurons of the n. accumbens weakens during presentation of conditioned stimuli only in "impulsive" animals, which is correlated with low network activity of the n. accumbens. Comparison of patterns of fronto-accumbal interactions during performance of the same type of activity revealed similar correlations in the neuronal pairs before and during presentation of conditioned stimuli, whereas different patterns corresponded to different types of activity.     

The model of the reward choice basing on the theory of reinforcement learning

We developed the model of alimentary instrumental conditioned bar-pressing reflex for cats making a choice between either immediate small reinforcement ("impulsive behavior") or delayed more valuable reinforcement ("self-control behavior"). Our model is based on the reinforcement learning theory. We emulated dopamine contribution by discount coefficient of this theory (a subjective decrease in the value of a delayed reinforcement). The results of computer simulation showed that "cats" with large discount coefficient demonstrated "self-control behavior"; small discount coefficient was associated with "impulsive behavior". This data are in agreement with the experimental data indicating that the impulsive behavior is due to a decreased amount of dopamine in striatum.     

The temporal organization of the functional connection of the motor cortex neurons in the cat]

Conditioned food-procuring response to time (2 minutes interval) was elaborated in cats, multiunit activity of the motor cortex being recorded. On the basis of single spike trains discriminated from the multiunit activity the cross-correlation histograms were built and the spikes composing their peaks were analysed in real time. This secondary analysis of the histograms allowed to ascertain the dynamics of functional connections between the neurons during the phase of active waiting according to the distribution of coincident impulses. A concentration of coincident impulses of simultaneously recorded cells was observed in different moment of time. In some neuronal pairs the concentration of coincident impulses was revealed to the end of the conditioned interval. The data obtained are considered as a manifestation of the conditioned reaction at the level of neuronal interaction.     

The organization of the network characteristics of the cells in local and distributed neuronal networks of the cat brain]

In cats with elaborated alimentary instrumental reflexes to light net characteristics of neurones of visual, motor cortex and the hypothalamus lateral nucleus were studied on the basis of revealed interneuronal interactions by means of cross-correlation method of analysis. Different organization of net properties of the cortical neurones in organization of local and distributed neuronal networks was shown, namely: predominance of the divergent characteristics over the convergent ones for cells in local networks and levelling of these relations in distributed nets. Neurones of the lateral hypothalamus nucleus had equal presentation of divergent and convergent properties in organization of local and distributed networks. Net characteristics of neurones of the cortical and subcortical structures were manifested in the background after the elaboration and the extinction of conditioned reflexes. Only small cells of the visual cortex were functionally dependent and changed correlation of net characteristics in local networks at CR extinction.     

A glimpse of the brain transforming a sensory signal into a motor response

Averages were made of neuronal spike activity recorded successively from eight relay regions along the auditorimotor pathway of naive cats and cats conditioned to blink in response to a 70 dB click conditioned stimulus (CS). It was hypothesized that the patterns of activity could be distinguished as sensory or motor by differences in their relationship to the pattern of the acoustic CS vs that of the conditioned response (CR). If so, it was also hypothesized that the acoustic stimulus would be better expressed at early auditorimotor relays and the motor response at later relays along the pathway. To test these hypotheses, Pearson correlation coefficients were calculated between the mean patterns of unit activity at each of the auditorimotor relays and (1) the rectified sound pattern of the CS and (2) the averaged, rectified electromyographic (EMG) activity of the muscles (orbicularis oculis) that produced the CR. In both naive and conditioned cats, there were significant positive correlations between the patterns of spike activity and the sound at early relays along the auditorimotor pathway such as the cochlear nucleus and inferior colliculus. In the conditioned animals, the spike activity of later nuclei in the auditorimotor pathway, such as the rostral thalamus and the motor cortex, had the highest positive correlations with the motor response. These correlations were low in the naive animals. Thus, the mean patterns of spike activity along the auditorimotor pathway appeared to distinguish the sound from the motor response and provided a glimpse of the process supporting transformation of the CS into the incipient CR.     

A glimpse of the brain transforming a sensory signal into a motor response

Averages were made of neuronal spike activity recorded successively from eight relay regions along the auditorimotor pathway of naive cats and cats conditioned to blink in response to a 70 dB click conditioned stimulus (CS). It was hypothesized that the patterns of activity could be distinguished as sensory or motor by differences in their relationship to the pattern of the acoustic CS vs that of the conditioned response (CR). If so, it was also hypothesized that the acoustic stimulus would be better expressed at early auditorimotor relays and the motor response at later relays along the pathway. To test these hypotheses, Pearson correlation coefficients were calculated between the mean patterns of unit activity at each of the auditorimotor relays and (1) the rectified sound pattern of the CS and (2) the averaged, rectified electromyographic (EMG) activity of the muscles (orbicularis oculis) that produced the CR. In both naive and conditioned cats, there were significant positive correlations between the patterns of spike activity and the sound at early relays along the auditorimotor pathway such as the cochlear nucleus and inferior colliculus. In the conditioned animals, the spike activity of later nuclei in the auditorimotor pathway, such as the rostral thalamus and the motor cortex, had the highest positive correlations with the motor response. These correlations were low in the naive animals. Thus, the mean patterns of spike activity along the auditorimotor pathway appeared to distinguish the sound from the motor response and provided a glimpse of the process supporting transformation of the CS into the incipient CR.     

Analysis of the level of cyclic adenosine-3',5'-monophosphate in structures of the 'informational' and 'motivational' system of the rat brain during active conditioning

The content of cyclic adenosine-3',5'-monophosphate (cAMP) was studied in structures of the "motivational" and "infromational" systems of rat brain after the active avoidance conditioning procedure in rats. Three groups of animals were examined: naive rats, trained (conditioned) rats, and group of the active control presented with uncombined conditioned (light) and unconditioned (electric footshock) stimuli. The content of cAMP was determined in the frontal cortex, hippocampus, amygdala, and hypothalamus of both hemispheres immediately after the retrieval of conditioned reaction one day after conditioning. A significant increase in cAMP level was bilaterally observed in the hypothalamus in the group of active control, and in both hippocampi and the right frontal cortex in the conditioned animals. Positive correlations between the cAMP levels in symmetrical regions of the frontal cortex, amygdala, and hypothalamus were revealed in all the examined groups. Additionally, intra- and interhemispheric correlations were found in the active control and conditioned rats. Patterns of correlation were specific for each of these groups. The observed phenomenon is discussed in term of involvement of "informational" and "motivational" brain structures in the mechanisms of adaptive behavior.     

Spatiotemporal Spike Coding of Behavioral Adaptation in the Dorsal Anterior Cingulate Cortex

The frontal cortex controls behavioral adaptation in environments governed by complex rules. Many studies have established the relevance of firing rate modulation after informative events signaling whether and how to update the behavioral policy. However, whether the spatiotemporal features of these neuronal activities contribute to encoding imminent behavioral updates remains unclear. We investigated this issue in the dorsal anterior cingulate cortex (dACC) of monkeys while they adapted their behavior based on their memory of feedback from past choices. We analyzed spike trains of both single units and pairs of simultaneously recorded neurons using an algorithm that emulates different biologically plausible decoding circuits. This method permits the assessment of the performance of both spike-count and spike-timing sensitive decoders. In response to the feedback, single neurons emitted stereotypical spike trains whose temporal structure identified informative events with higher accuracy than mere spike count. The optimal decoding time scale was in the range of 70–200 ms, which is significantly shorter than the memory time scale required by the behavioral task. Importantly, the temporal spiking patterns of single units were predictive of the monkeys’ behavioral response time. Furthermore, some features of these spiking patterns often varied between jointly recorded neurons. All together, our results suggest that dACC drives behavioral adaptation through complex spatiotemporal spike coding. They also indicate that downstream networks, which decode dACC feedback signals, are unlikely to act as mere neural integrators.     

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.     

Cooperative activity of motor and frontal cortex neurons in trained cats systemically administered M-cholinoreceptor blockers]

It was shown previously that peripherally administered antagonists of the central 1 M-cholinoreceptors led to a selective impairment of bar-pressing response in a food-reinforced operant conditioned task but did not alter contextual behavior and functions such as motivation, perception, and locomotion. To obtain information about the central mechanisms of the conditioning impairment, we recorded simultaneously the extracellular multiunit activity from the frontal and motor neocortical areas of five cats trained to acquisition criteria in a food-reinforced operant conditioning task. Multiunit recordings were performed drur 1) normal conditioning; 2) conditioning during subcutaneous administration of muscarinic antagonists scopolamine (0.03 mg/kg), trihexyphenidyl (1 mg/kg), and methylscopolamine (0.03 mg/kg). Autocorrelation analysis showed that scopolamine and trihexyphenidyl but not methylscopolamine led to a significant increase in the tendency of cortical cells to fire in a cyclic way (i.e., the shift of the firing pattern from a single-spike discharge to burst, rhythmic, or rhythmic-burst discharge) both in the motor and frontal areas. Cross-correlation analysis showed that the bursting and rhythmic-bursting cells synchronized their activity within and (in a number of cases) between the cortical areas. These changes in the neuronal activity within the motor cortex and frontal cortex were accompanied by a significant decrease in the functional connectivity both inside and between the cortical areas in parallel with selective impairment of the conditioned response.     

A model for the neuronal implementation of selective visual attention based on temporal correlation among neurons

We propose a model for the neuronal implementation of selective visual attention based on temporal correlation among groups of neurons. Neurons in primary visual cortex respond to visual stimuli with a Poisson distributed spike train with an appropriate, stimulus-dependent mean firing rate. The spike trains of neurons whose receptive fields donot overlap with the focus of attention are distributed according to homogeneous (time-independent) Poisson process with no correlation between action potentials of different neurons. In contrast, spike trains of neurons with receptive fields within the focus of attention are distributed according to non-homogeneous (time-dependent) Poisson processes. Since the short-term average spike rates of all neurons with receptive fields in the focus of attention covary, correlations between these spike trains are introduced which are detected by inhibitory interneurons in V4. These cells, modeled as modified integrate-and-fire neurons, function as coincidence detectors and suppress the response of V4 cells associated with non-attended visual stimuli. The model reproduces quantitatively experimental data obtained in cortical area V4 of monkey by Moran and Desimone (1985).     

Correlation of evoked potentials in the frontal cortex and hippocampus of cats in emotional stress

Averaged auditory evoked potentials (AEPs) were recorded in symmetric points of the frontal cortex and dorsal hippocampus of cats performing acquired conditioned food-procuring reaction reinforced in 100% cases, urgent transition to 30%-reinforcement, and return to 100%-reinforcement. Emotional stress estimated by a heart rate rise developed during increased food motivation of a cat as well as during change in ordinary food-procuring stereotype. The emotional stress was accompanied by a high positive correlation of cortical and hippocampal AEPs. Decrease in the stress level led to a drop between AEP correlations and appearance of their negative values. In emotional stress, the interactions between the frontal cortex and dorsal hippocampus were asymmetric: right-side correlations were higher.     

Local and distributed neuronal networks and individuality

To estimate stable behavioural peculiarities, an individual varying choice of greater or better appetite reinforcement depending on the time of instrumental motor response was used with cats. A decisive role in realisation of the response choice is played by the influence of motivational structures of hypothalamus and amygdala on formal areas of neocortex typical for "impulsive" (fast reacting) cats, and interaction of the frontal cortex--hippocampus system for the animals with delayed pressing of the lever to obtain their preferred food, i.e. manifesting the ability of "self-control".     

Recurrence plots of neuronal spike trains

The recently developed qualitative method of diagnosis of dynamical systems — recurrence plots has been applied to the analysis of dynamics of neuronal spike trains recorded from cerebellum and red nucleus of anesthetized cats. Recurrence plots revealed robust and common changes in the similarity structure of interspike interval sequences as well as significant deviations from randomness in serial ordering of intervals. Recurring episodes of alike, quasi-deterministic firing patterns suggest the spontaneous modulation of the dynamical complexity of the trajectories of observed neurons. These modulations are associated with changing dynamical properties of a neuronal spike-train-generating system. Their existence is compatible with the information processing paradigm of attractor neural networks.     

The typological characteristics of higher nervous activity in dogs and the maxima of the cross-correlation function between the electrical activities of the frontal cortex and the brain limbic systems]

Electrical activity of the frontal cortex, dorsal hippocampus, basolateral amygdala and lateral hypothalamus was recorded in eight dogs with chronically implanted electrodes. Mean values of the maxima of crosscorrelation function (MCCF) between electrical potentials in the theta, alpha and beta-2 ranges were used as a basis for assessment of conditions for interaction between these structures. Typological features of the higher nervous activity were assessed by the animal performance under conditions of free choice of the reinforcement mode of a conditioned stimulus: either high probable but of low alimentary quality or with low probability but more valuable. The mean MCCF values in the theta range were higher than in the other ranges. The brain structure which had the high MCCF in the theta-range, at least, with two of the structures under study was considered as "dominant". It was shown that hippocampus was the dominant structure for melancholic dogs, the frontal cortex was in phlegmatics. The hypothalamus was shown to be the "dominant structure" in both sanguine and choleric animals, but, for the most part, its activity was correlated with different structures. Thus, conditions for interaction between the frontal cortex, hippocampus, amygdala and hypothalamus seem to be an important factor, which determines typological features of the higher nervous activity of dogs.     

The intercentral relations of the frontal cortex and limbic structures of the brain in dogs]

In 3 dogs with implanted electrodes, in conditioned experiments correlation of the bioelectrical processes was studied by coherence function calculation of the hippocampus, hypothalamus, amygdala and frontal cortex biopotentials. It was shown, that the level of maximum values of coherence function of bioelectrical oscillations, led from various pairs of the studied brain structures significantly differed both in magnitude and frequency at which the greatest synchronization of biopotentials was noticed. In one dog with a high degree of connection between the hippocampus and hypothalamus biopotentials oscillations, a low synchronization of the frontal cortex and amygdala oscillations was found; in two other animals with a higher level of coherence between the oscillations of the frontal cortex and amygdala biopotentials, a lower degree of connection between the oscillations led from the hippocampus and hypothalamus was revealed. Synchronization of the biopotentials of the hippocampus and frontal cortex and also of the hippocampus and amygdala biopotentials proved to be low in all experimental dogs, what additionally testifies to different role of these structures in organization of the behaviour.