Cooperative activity of neurons in the nucleus accumbens and frontal cortex in cats trained to select reinforcements of different value.

Results obtained at the level of the organization of interneuronal interactions of cells in the nucleus accumbens and frontal cortex revealed the features of the involvement of this component in "impulsive" and "self-controlled" behavior, consisting of an increase in bidirectional interactions between the structures of interest, accompanied by simultaneous reductions in the regularity of interactions with increases in "impulsivity" and decreases in "self-control." Long-latency reactions appearing only in "impulsive" animals were associated with decreases in the control of frontal cortex cells by the nucleus accumbens during the signal period, which correlated with the low activity of the network activity of the nucleus accumbens in these animals. Comparison of the patterns of frontal-accumbens interactions as the animals performed a single type of activity demonstrated that the connections in neuron pairs during the presignal and signal periods were similar, while significant differences in patterns were seen during the performance of different types of activity.

Organization of interneuronal connections in the nucleus accumbens in "impulsive" and "self-controlled" behavior in cats.

In behavioral experiments, cats placed in a situation of choosing between a high-value time-delayed and a low-value rapid food reinforcement elected to wait for the preferred reward (they demonstrated "self-control") or to obtain the worse reward quickly (they demonstrated impulsive behavior). On the basis of the selected behavioral strategy, the cats were divided into three groups - "impulsive," "ambivalent," and "self-controlled." Cross-correlation analysis was used to assess the linked activity of cells in the nucleus accumbens, which reflects the nature of interactions between close-lying neurons. In cats with self-control, interneuronal interactions appeared in a significantly larger proportion of cases than in impulsive cats. In combinations resulting in long-latency reactions, cats with self-controlled and impulsive behavior showed no significant difference in the occurrence frequency of interneuronal interactions. The numbers of interneuronal interactions were greater during erroneous responses as compared with correctly performed reactions in animals of the different groups. These data indicate a key role for the interrelated activity of nucleus accumbens neurons in organizing the pattern of long-latency responses typical of self-controlled behavior.

Interactions between neurons in the frontal cortex and hippocampus in cats trained to select reinforcements of different value in conditions of cholinergic deficiency.

An operant food-related conditioned reflex was developed in six cats by the "active choice" protocol: short-latency pedal presses were followed by presentation of low-quality reinforcement (bread-meat mix), while long-latency pedal presses were followed by presentation of high-quality reinforcement (meat). Animals differed in terms of their food-procuring strategies, displaying "self-control," "ambivalence," or "impulsivity." Multineuron activity was recorded from the frontal cortex and hippocampus (field CA3). Cross-correlation analysis of interneuronal interactions within (local networks) and between (distributed networks) study structures showed that the numbers of interneuronal interactions in both local and distributed networks were maximal in animals with "self-control." On the background of systemic administration of the muscarinic cholinoreceptor blockers scopolamine and trihexyphenidyl, the numbers of interneuronal interactions decreased, while "common source" influences increased. This correlated with impairment of the reproduction of the selected strategy, primarily affecting the animals' self-controlled behavior. These results show that the "self-control" strategy is determined by the organization of local and distributed networks in the frontal cortex and hippocampus.

Organization of frontohippocampal neuronal networks in cats in different types of directed behavior.

Food-related operant conditioned reflexes to light were developed in four cats on the basis of the "active choice" of reinforcement quality: short-latency pedal presses were reinforced with a mixture of meat and bread, while long-latency presses were reinforced with meat. Animals showed differences in their behavioral strategies: two preferred long-latency pedal presses (animals with "self-control"), while the other two preferred short-latency pedal presses ("impulsive" animals). At the second stage of the study, animals of both groups were retrained to a short-delay (1 sec) conditioned operant food-related reflex in response to light with meat reinforcement. Chronically implanted Nichrome semimicroelectrodes were used to record multicellular activity in the frontal cortex and hippocampus (field CA3). The interaction of neighboring neurons within the frontal cortex and hippocampus (local neural networks) and neurons of the frontal cortex and hippocampus (distributed frontohippocampal and hippocampofrontal neural networks) were assessed by statistical cross-correlation analysis of spike trains with an analysis epoch of 100 msec. The frontal and frontohippocampal neural networks had different modes of functional organization in the simplified task for the animals of the two groups. However, intergroup differences in local networks of the hippocampus persisted in conditions of the simplified task lacking the requirement for the animals to select the quality of the reinforcement, indicating the likely genetic determinacy of these networks.

Interneuronal frontohippocampal interactions in cats trained to choose on the basis of reinforcement quality.

Six cats were trained to food-related operant conditioned reflexes to light using the "active choice" of reinforcement method: short-latency pedal pressings were reinforced with meat and bread, while long-latency responses were reinforced with meat. Animals were divided in terms of their behavioral strategies: four preferred long-latency pedal pressings (the "self-controlled" group), while the other two preferred short-latency pedal pressings ("impulsive" animals). Implanted Nichrome semimicroelectrodes were used to record multicellular activity in the frontal cortex and hippocampus (field CA3). Interactions of neighboring neurons within the frontal cortex and the hippocampus (local neuronal networks) and between frontal cortex and hippocampal neurons (distributed neural networks in the frontohippocampal and hippocampofrontal directions) were assessed by statistical cross-correlation analysis of spike series with analysis epochs of 100 msec. The number of cross-correlational connections between the discharges of neurons in both local and distributed networks were significantly greater in the group of animals demonstrating self-control, i.e., preferring long-latency pedal pressings to receive the more valuable reinforcement. It is suggested that the predominance of functional interneuronal connections in the local networks of the frontal cortex and hippocampus and in frontohippocampal distributed networks in animals operating in the self-control regime as compared with impulsive animals demonstrates the dominant role of these informational structures in the organization of self-controlled behavior.

Organization of neural networks in the neocortex.

Implanted semimicroelectrodes were used in conscious cats to record spike discharges from groups of close-lying neurons, i.e., multineuron activity, in the deep layers of the frontal and motor areas of the cortex at different levels of food motivation. Spike activity was extracted from 4-7 neurons and interneuronal interactions were studied by cross-correlation analysis between neighboring neurons in each zone (local networks) and between neurons in two zones (distributed networks) with analysis epochs of 0-100 msec. The results showed that neurons in local networks can be divided into two subgroups: neurons with high-amplitude spikes and a predominance of output (divergent) connections and neurons with low-amplitude spikes and a predominance of input (convergent) connections. Local networks are based on powerful monosynaptic connections (with delays of up to 2 msec) between large and small neurons. Most connections in distributed networks were between small neurons in local networks of the frontal cortex and large neurons in local networks in the motor cortex. Food deprivation for 24 h mainly affected late (with delays of 2-100 msec) cross-correlation interneuronal relationships in both local and distributed networks.

Network activity in neurons of the motor and prefrontal areas of the cortex in trained cats in conditions of systemic administration of m-cholinoreceptor blockers.

Experiments on five cats already trained to an operant conditioned food-procuring reflex to light were used to study the network activity of cells in the frontal and motor areas of the cortex accompanying disruption of conditioned reflex behavior in conditions of systemic administration of m-cholinoreceptor blockers. The activity of cortical neurons and their network properties were assessed using auto- and cross-correlation histograms. Doses of central m-cholinoreceptor blockers (the non-selective blocker scopolamine and the relatively selective m1-cholinoreceptor blocker trihexyphenidyl) disrupted performance of the operant motor reflex but had no effect on the appearance of contextual behavior and responses to switching on of the conditioned signal (standing up, elevating the paw). This was accompanied by 1) changes in the patterns of neuron activity in the moor and frontal areas of the cortex, with increases in train, rhythmic, and rhythmic train activity in cortical cells; 2) appearance of synchronicity in the operation of cortical neurons; 3) decreases in the numbers of direct interneuronal connections in the motor and frontal areas of the cortex and in the numbers of connections between these structures.

Functional organization of local neural networks in the cat neocortex. Relationship to the level of food motivation.

Implanted semimicroelectrodes were used to record multineuron activity--spike discharges from groups of close-lying neurons--in the deep layers of the frontal and motor cortex in conscious cats with different levels of food motivation. Spike activity from 4-7 neurons was extracted from multineuron activity, and interneuron interactions were studied by cross-correlation analysis. Neurons in local networks were divided into two subgroups: neurons with high-amplitude spikes with a predominance of output (divergent) connections, and neurons with low-amplitude spikes and a predominance of input (convergent) connections. Food deprivation lasting 24 h affected mainly the nature of interneuron interactions in the range of late cross-correlational connections (with delays of 2-100 msec).

The role of muscarinic cholinoceptors in the retrieval of an operant food-related conditioned reflex in cats.

Experiments on cats showed that lesions affecting retrieval of an operant food-procuring reflex. occurring on a background of systemic administration of the centrally-acting muscarinic cholinoceptor blocker scopolamine (a non-selective M-cholinoceptor blocker) and trihexyphenidyl (a relatively selective M1-cholinoceptor blocker), might be associated with the central and peripheral side effects of these blockers, preventing performance of the conditioned reflex. It was established that when no side effects were present (low doses of trihexyphenidyl, 1 mg/kg), blockade of M1-cholinoceptors led to selective loss of the motor operant reflex while contextual behavior and other conditioned responses were retained or led to errors in performance of the reflex: this appears to be evidence that derangement of launching and performing the motor program is the most important component of the conditioned reflex. Systemic administration of trihexyphenidyl at a dose of 10 mg/kg, scopolamine at doses of 0.03 and 0.06 mg/kg, and the peripherally-acting non-selective blocker methylscopolamine at a dose of 0.03 mg/kg led to changes in the general functional state (disturbances in the emotional-motivational sphere), the extent of which depended on the individual sensitivity of the animal to the anticholinergic agents. The presence of side effects led to complete cessation of conditioned reflex activity, though this appeared not to be associated with memory impairment.

Interactions between neurons in the amygdala and hypothalamus during conditioned reflex behavior involving choice of reinforcement quality in cats.

The organization of distributed amygdalo-hypothalamic and local amygdalar and hypothalamic neural networks was studied in three cats, trained to perform a food-related operant conditioned reflex to light by the "active choice" of reinforcement quality method; pressing the pedal with a short latent period provided the cats with a bread/meat mixture, while pressing with a long latent period yielded meat. Animals showed sharp differences in their individual abilities to choose one or the other reinforcement. Two cats preferred long-latency pedal-pressing to obtain meat, and were considered to be "self-controlled," while the third cat, which preferred short-latency pedal-pressing to obtain the less valuable reinforcement (the bread/meat mixture) was described as "impulsive." Chronically implanted semimicroelectrodes were used to record multineuron activity in the basolateral nucleus of the amygdala and the lateral nucleus of the hypothalamus. Interactions between the discharge trains of neighboring and distant neurons were assessed by cross-correlation analysis. Interneuron functional connections were found to predominate significantly in the local neural networks of the basolateral amygdala and distributed amygdalar-hypothalamic networks in the "impulsive" animal as compared with the "self-controlled" animals, suggesting a role for these types of connection in forming the individual characteristics of higher nervous activity. The identical incidences of interneuron interactions in the lateral nucleus of the hypothalamus in cats with different individual preferences suggest that local networks in this formation are not involved in analyzing reinforcement quality.

Interneuron relationships in the basolateral amygdala in cats treated to select food on the basis of quality.

Cats were initially trained to make operant conditioned food responses to light by an "active selection of reinforcement" method. Provision of low-quality (a mixture of meat and bread) or high-quality (meat) reinforcement depended on the animal pressing a pedal in response to switching on a light with a short (1 sec) or long (10 sec) delay. Some animals responded to long delays--group I, animals with "self control," while others responded with short delays--group II, "impulsive" animals. Implanted semimicroelectrodes were used in chronic experiments to record multineuron activity in the basolateral amygdala. Cross-correlation analysis was used to study interneuron interactions in the spike discharges of individual neurons, extracted from multineuron activity. The numbers of interneuron interactions were significantly higher in "impulsive" cats of group II in all behavioral situations than in animals with "self control," and were dominated in "impulsive" animals by the shortest connections, with latencies of 0-30 msec. The largest numbers of connections in both groups were seen on omission of the conditioned pedal-pressing movement response, i.e., when the reinforcement selection task was more difficult. These data indicate that the basolateral amygdala should be regarded as a structure determining the individual typological characteristics of the animals' behavior.

Time organization of frontal-motor cortex interneuron interactions in the cat neocortex in conditions of different levels of food motivation.

Studies were carried out in conscious cats with recording of multicellular activity in moderate hunger and after 24-h food deprivation. Cross-correlation analysis was used to assess statistical interneuron interactions between closely-located neurons in the frontal and sensorimotor regions of the neocortex (local networks), and between the cells of these regions (distributed networks). One-day food deprivation increased the number of interactions formed within both local and distributed neuron networks. Increases in intercortical connections between the frontal and motor regions was seen at all time intervals studied (0-100 msec), though the most significant changes occurred at time intervals of up to 30 msec.

Interneuronal functional associations in the sensorimotor cortex of dogs.

The interneuronal functional associations were studied in two dogs with Nichrome semi-microelectrodes implanted into the deep layers of the motor and somatosensory regions of the cerebral cortex using the method of cross-correlation analysis. For this purpose the impulse activity of individual neurons was distinguished by form from the background multineuronal activity using the spike recognition technique. Values of a 0.5 and 1 msec-wide bin, and thereafter with a 1 msec step up to 40 msec, were used to plot the cross-interval histograms. The maximal analysis epoch was 2000 msec. The cross-interval associations were monotypal in character; they all presented fairly narrow extrema which were clearly distributed across three time ranges: short-latency associations up to 10 msec; associations with a medium latency up to 80 msec; and associations with late delays, greater than 80 msec. The fairly narrow peak of the association, especially in the case of associations with late delays, was a very difficult phenomenon to explain from the point of view of traditional theoretical perspectives. It is hypothesized that a mechanism exists in the cortex which is responsible for strictly synchronized and highly efficient synaptic transmission.

Conditioned avoidance reflex and intersignal movements: interrelationship of cardiac and motor components.

The correlation of the heart rate (HR), of a conditioned motoric reaction, and intersignal movements was studied during the development of a conditioned reflex (CR) of avoidance using V.P. Petropavlovskii's methods. The level of defensive motivation, assessed on the basis of the magnitude of changes in HR was maximal against the background of a firmly developed CR during the course of the latent period of the conditioned motoric reaction. A sharp decrease in the level of defensive excitation took place against the background of the latter, expressed in the prolonged holding of the extremity in place in the safety zone (height of rise 5-10 cm, guaranteeing the avoidance of electrodermal stimulation of the extremity). Intersignal movements of two types were described: the first in the form of phasic flexions; the second repeats the conditioned motoric reaction of the holding of the extremity in place. A reduction in defensive excitation took place against the background of the latter, like that which took place during the elevation of the extremity against the background of the combination.

Cortical multineuronal activity in dogs with defensive instrumental conditioned reflex.

For the first time in dogs with semi-microelectrodes chronically implanted in the motor and somatosensory region of the cortex, background multineuronal activity (MNA) was recorded over the long term followed by an amplitudinal discrimination from the MNA of impulse series presumably belonging to cells of large, medium, and small size was performed. The presence of close synergistic functional connections, particularly significant during the avoidance conditioned reflex and its extinction, was established by determining the correlation coefficient (CC) between the impulse flows of these neurons. In trained animals the highest CC values were observed between neurons with a small and medium spike amplitude. The network properties of identified neurons were studied by constructing histograms of cross interval relationships. The connections established were of primarily a unilateral, excitatory character.