A comparative neuropsychological approach to the analysis of hippocampal functions

Formation of conditioned switching-over of heterogeneous instrumental reflexes in dogs was more successful than in rats, which testifies about significant differences of the functional organization of analytical-synthetic brain activity in rodents and predatory animals. Experiments with lesion of the hippocampus (in rats) and the records of its electrical activity (in dogs) allowed to conclude that the hippocampus of the both types of animals belongs to the system of structures, participating in the formation of conditioned switching-over. The data, obtained in the process of elaboration of the switching-over and probabilistic reinforcement of the alimentary conditioned stimulus, testify that providing for the reactions to signals with low probability of reinforcement in different species of animals is one of the functions of the hippocampus.     

Does heart rate differentiate neurotic from normal people in a conditional reflex test?

This study is to compare heart reactivity between normals and anxiety neurotic patients. Five male and five female patients with anxiety neurosis and four male and five female normal persons were submitted to classic delayed conditional reflexes with different probabilities of reinforcement (shock), to a defensive instrumental conditional reflex, and to a neutral nonreinforced stimulus. The basal heart frequency was higher in neurotics and in women than in normals and men. The conditional stimulus (CS) associated with a shock generally produced a bradycardia in normal individuals and in neurotic men, but a tachycardia in neurotic women (effects most pronounced in cases with 100% shock probability). The instrumental CS caused a tachycardia in all of the groups, with highest values in neurotic women. The neutral stimulus produced bradycardia in all persons. The aftereffect of the light stimulus depended on whether a shock was administered and on the CS. The differences between neurotics and normals are explained as caused by the heightened excitatory level of the CNS of the neurotic group, produced by the unspecific activating effect of chronic anxiety, and differences of plastic processes in both groups, resulting in different effects of phasic anxiety on the heart. Complex inhibitory-excitatory interactions of the sympathetic and the vagal system underlying the heart rate changes may be assumed. Possible mechanisms leading to sex differences are discussed.     

Instrumental heterogeneous responses to 2 successive complex stimuli with a common initial stimulus in the dog

Formation and achievement of heterogenous instrumental reflexes to two consecutive complex stimuli was studied in dogs. Under the action of conditioned complex stimulus tone--Pause--tone, the dogs may be trained not to have a motor response to the first tone presentation, but perform alimentary instrumental reaction only to its repeated administration. Introducing into the experiment not only alimentary but also defensive complex stimulus stone-pause--light resulted in a change in animal's reactions in such a sequence: at first alimentary instrumental reaction was disinhibited under the action of the preparatory stimulus and during the pause, then bieffector responses appeared, further on in most of the dogs motor defensive reactions mainly took place. Trigger stimuli evoked the adequate instrumental reaction.     

Conditioned reflex and electrical activities of the hippocampus during the random use of heterogeneous triggering stimuli

In dogs with electrodes chronically implanted in the hippocampus, the conditioned activity, heart rate frequency and spectral characteristics of the hippocampal theta-rhythm were studied in conditions of irregular presentation after a preparatory stimulus now of alimentary and now of defensive triggering conditioned stimuli. It is shown that uncertainty of alimentary or defensive reinforcement is a stronger emotiogenic factor than the action of the triggering defensive conditioned stimulus. Changes in electrical hippocampal activity and autonomous activity depend, along with other factors, on forecasted volume of the forthcoming motor activity. The speed of instrumental conditioned reflexes formation correlates with the hippocampal theta-rhythm frequency, typical for the given animal.     

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.     

Activity of neurons in the pedunculopontine nucleus in conditioned instrumental appetitive reflex

Activity of 91 neurons in the compact and diffuse parts of the pedunculopontine tegmental nucleus (PPTg) was recorded in freely moving rabbits during execution of instrumental appetitive conditioning. Of the recorded neurons, 37.4% changed their activity in response to a conditioned stimulus, which is the evidence for the PPTg involvement in instrumental conditioning. Excitatory conditioned neuronal responses to the conditioned stimulus and food reinforcement significantly prevailed over inhibitory reactions. Neuronal responses to the conditioned stimulus were classified in several basic patterns reflecting stimulus effects, structure of the behavioral act, and reinforcement properties. These reactions indicate the involvement of the PPTg in attention, motor learning, and reinforcement. The revealed differences in associative reactive properties of the compact and diffuse parts of the PPTg to the conditioned stimulus and reinforcement point to the functional heterogeneity of this structure and suggest the leading role of the cholinergic part of the PPTg in instrumental appetitive conditioning and reinforcement as well as the essential contribution of the diffuse part into classical appetitive conditioning.     

Autonomic correlates of the formation of a functional self-stimulation system

Capability of intracerebral electrostimulation to serve as an unconditioned reinforcing stimulus in classical conditioning was studied in rabbits. Changes of such vegetative characteristics as respiration frequency and ECG were taken as criterion of conditioned response (CR) elaboration. In preliminary experiments, optimal parameters of stimulation maintaining the highest level of instrumental self-stimulation behaviour were found for each of the animals. Isolated presentation of the unconditioned reinforcing stimulus led to the increase of respiratory rate. Such kind of stimulation induced tachicardia in 5 animals, bradicardia in 3 ones, and in the remaining 6 rabbits a biphasic reaction was observed with initial tachicardia changing for bradicardia. Reactions were taken as CRs if they were similar to those to the unconditioned stimulus and appeared at the moment of omitted reinforcement. After 10 pairings of conditioned sound stimulus with positive reinforcement, CR changes of the two vegetative parameters were observed in 21,4 per cent of cases. After 40 pairings CRs were observed in 87,5 per cent of trials for cardiac and in 78,5 per cent cases for respiratory components. The results obtained confirm the idea of validity and efficiency of intracerebral stimulation of self-stimulation zones as a factor of positive reinforcement.     

Characteristics of the systemic organization of the cortical neurons in various forms of the manifestation of the conditioned reflex to time

Conditioned food-procuring reflex to time (2 minutes interval) was elaborated in cats. By the method of cross-correlative analysis the combined neurones activity in microareas and between microareas of the motor cortex was compared at various forms of conditioned reflex manifestation. Three types of reactions were considered: A--decrease of respiratory movements amplitude towards the end of the studied interval between reinforcement; B--increase of the amplitude; C--food-procuring paw movement a few seconds before the reinforcement. All three forms of the conditioned reflex to time differed from each other by the level of increase of functional connections number by the moment of the reinforcing stimulus action, and also to a greater extent by the frequency of occurrence of intervals in which the sum of neuronal connections in all simultaneously recorded microareas was greater in the "active" phase than in the "inactive" one. These parameters did not always correlate with the change of impulses frequency of separate neurones which occurred considerably more seldom. All the observed changes were manifest significantly more often when the animals performed the instrumental food-procuring movement than during changes of only the respiratory movements amplitude.     

The characteristics of the neuronal reactions of the cat somatosensory cortex to a heteromodal complex conditioned signal]

On alert cats the change was studied of the activity of the neurones of the sensorimotor cortical area at instrumental reaction to a simultaneous heteromodal complex stimulus. It was shown that in the projection of distal limb areas a group could be singled out of neurones, which changed their activity in one direction depending on the character of presented signals. In these cells an increase of discharges frequency was observed in response to complex stimulus, consisting of light and sound signals. After the extinction of the motor reaction both to the complex stimulus and to its components neuronal reactions of lesser intensity was recorded, what determined the absence of the motor reaction. This group of neurones had receptive fields localized on distal limb areas, it was activated at fulfillment of the movement of catching the reinforcement and belonged to neurones of the pyramidal tract. The neurones with receptive fields on the whole limb surface or changing their activity at the animal pose change, had variable reactions to positive and differentiation stimuli.     

The conditioned avoidance reflex and intersignal movements: the correlation of the cardiac and motor components]

In five dogs correlation was studied of heart rate (HR) and motor component of conditioned avoidance reflex (CAR), elaborated by Petropavlovski? method. Stable CAR was expressed in lifting and long (not less than 5-10 sec) holding of the paw on definite height (5-10 cm) for the avoidance of painful electrocutaneous paw stimulation in response to conditioned acoustic stimulus. The level of defensive excitation, evaluated by heart rate change was maximum before the beginning of the conditioned motor reaction. Immediately after lifting and placing the paw in the zone of security a sharp decrease of defensive excitation level ("drive" reduction) took place. Intertrial motor reactions of two types were revealed. The first type imitated the conditioned motor reaction, the second one the usual phasic bending of the paw. Against the background of intertrial movement of the first, operant type a decrease of defensive motivation took similarity as it occurred against the background of CAR during the performance response.     

Effects of prefrontal ablations on the reaction of the active choice of feeder under different probability and value of the reinforcement on dog

The role of the prefrontal cortex was investigated on the reaction of the active choice of the two feeders under changes value and probability reinforcement. The experiments were performed on 2 dogs with prefrontal ablation (g. proreus). Before the lesions the dogs were taught to receive food in two different feeders to conditioned stimuli with equally probable alimentary reinforcement. After ablation in the inter-trial intervals the dogs were running from the one feeder to another. In the answer to conditioned stimuli for many times the dogs choose the same feeder. The disturbance of the behavior after some times completely restored. In the experiments with competition of probability events and values of reinforcement the dogs chose the feeder with low-probability but better quality of reinforcement. In the experiments with equal value but different probability the intact dogs chose the feeder with higher probability. In our experiments the dogs with prefrontal lesions chose the each feeder equiprobably. Thus in condition of free behavior one of different functions of the prefrontal cortex is the reactions choose with more probability of reinforcement.     

Impulse activity of neurons of the visual and somatosensory regions of the cerebral cortex at different stages of goal-directed behavior

Impulse activity of neurones of the visual and somatosensory cortical areas was studied in free moving cats during performance of conditioned instrumental food-procuring reactions to the presentation of light or sound. It was established that the units of these cortical areas may participate in both all or individual stages of complex instrumental behaviour. The visual cortex neurones are more extensively involved in the formation of successive stages of the goal-directed behavioral act. Significant differences were revealed in the unit responses of the visual and somatosensory cortical areas at the moment of the switching on of the conditioned signal, at the period of "reinforcement anticipation", at the moment of appearance of milk, the reinforcing agent, and during reinforcement, when the milk was lapped by the animal.     

The effect of electrostimulation of the caudate nucleus and somatosensory cortex on defensive instrumental reactions in dogs]

It has been shown that the effect of stimulation of the caudate nucleus head in the contralateral hemisphere differs at different stages of achievement of a defensive instrumental habit in dogs. Stimulation preceding the action of the conditioned signal or delivered simultaneously with the beginning of the latter did not change the criteria for the achievement of successive programs of the instrumental defensive reaction. Stimulation of the same areas in the last phase of the instrumental response, as a rule, lead to the cessation of instrumental movement. A conclusion has been drawn that in a defensive situation the inhibitory influence of the caudate nucleus on instrumental behaviour of intact dogs is not so sharply expressed as in experiments with alimentary reinforcement. In dogs with a preliminary ablation of the CI and CII cortical zones of the contralateral hemisphere, stimulation of the caudate nucleus head was attended with a sharp drop in every criterion of the instrumental defensive reactions.     

Formation of temporary connections in dogs following destruction of the amygdaloid complex, head of the caudate nucleus and orbital cortex]

Ablation of the orbital cortical zones in dogs after ablation of the basolateral part of the amygdala and the caudate nucleus head considerably impeded the elaboration of secretory conditioned alimentary reflexes, without affecting the rate of elaboration of simple instrumental food-procuring reaction. The dogs lost however the capacity to differentiate non-reinforced stimuli from reinforced ones, which was revealed in both secretory and instrumental reactions.     

Effect of electrocoagulation of the septum on the behavior and memory of the cat

Lesion effects of various areas of the septum on general behaviour, learning and memory were studied in cats. It appeared that electrocoagulation of the medial septum alone leading to the disappearance of the hippocampal theta rhythm does not result in the development of the septal syndrome signs; does not disturb the normal structure of the sleep-wakefulness cycle; does not delay the elaboration of instrumental alimentary reflexes (to approach two feeders) or their extinction, but does entirely disturb the delayed responses to conditioned stimuli. In cases when lesion involves also the lateral septum, it produces the development of all signs of the septal syndrome (hyperemotionality, hyperactivity, rage, hyperphagia, etc.), disturbance of the normal structure of the sleep-wakefulness cycle, delay of both the elaboration and extinction of instrumental alimentary reflexes, disturbance of pre-elaborated conditioned reactions with sound discrimination, entire disturbance of conditioned delayed responses. On the basis of these data, the specific significance of hippocampal theta-rhythm in the organization of learning and memory is rejected, and a more important role is attributed to the descending regulatory influence exerted by the hippocampus and other archipaleocortical structures on the activating and motivatiogenic structures of mesodiencephalon.     

Neuronal activity in the nucleus basalis magnocellularis during performance of an instrumental task

Spike activity of 95 neurons in the rabbit basal forebrain forebrain magnocellular nucleus was recorded during spontaneous behavior and instrumental conditioned performance. Almost half of the neurons (48.4%) displayed a significant (p > 0.05) negative correlation between their spontaneous discharge rate and the power of the delta rhythm in the EEG of the frontal cortex; most of these cells can be classified as projection cholinergic neurons. During instrumental conditioned performance, neurons of this subgroup responded with excitation to the conditioned stimulus, whereas presumably noncholinergic nonprojection neurons responded to the conditioned stimulus with inhibition. Excitatory response of cells in the basal forebrain magnocellular nucleus was significantly more intense as compared to trials without the conditioned reaction. On the whole, our data testify that the basal forebrain magnocellular nucleus maintains the level of arousal and attention required for the instrumental conditioned performance.     

Choice between probability and value of alimentary reinforcement as means for revealing individual typological features of dog behavior

Individual typological features of behavior of dogs were investigated by the method of choice between the low-valuable food available constantly and food of high quality presented with low probability. Animals were subjected to instrumental conditioning with the same conditioned stimuli but different types of reinforcement. Depression of a white pedal was always reinforced with meat-bread-crumb mixture, depression of a black pedal was reinforced with two pieces of liver (with probabilities of 100, 40, 33, 20, or 0%). The choice of reinforcement depended on probability of valuable food and individual typological features of the nervous system of a dog. Decreasing the probability of the reinforcement value to 40-20% revealed differences in behavior of dogs. Dogs of the first group, presumably with the weak type of the nervous system, more frequently pressed the white pedal (always reinforced) than the black pedal thus "avoiding a situation of risk" to receive an empty cup. They displayed symptoms of neurosis: whimper, refusals of food or of the choice of reinforcement, and obtrusive movements. Dogs of the second group, presumably with the strong type of the nervous system, more frequently pressed the black pedal (more valuable food) for the low-probability reward until they obtained the valuable food. They did not show neurosis symptoms and were not afraid of "situation of risk". A decrease in probability of the valuable reinforcement increased a percentage of long-latency depressions of pedals. It can be probably suggested that this phenomenon was associated with increasing involvement of cognitive processes, when contributions of the assessments of probability and value of the reinforcement to decision making became approximately equal. Choice between the probability and value of alimentary reinforcement is a good method for revealing individual typological features of dogs.     

Individual typological characteristics of higher nervous performance and asymmetry of hippocampus and amygdala electrical activity in dogs

Electrical activity of the frontal cortex, dorsal hippocampus, basolateral amygdala and lateral hypothalamus of both hemispheres was recorded in nine dogs in the state of quiet wakefulness without any stimulation. Individual typological features of higher nervous activity were assessed by the animal performance under conditions of free choice of the reinforcement mode: either high probable but of low alimentary quality, or with low probability but more valuable. Mean values of the maxima of crosscorrelation function between electrical activity of the investigated structures of two hemispheres were used as a basis for assessment of conditions for interaction between left and right formations. For the hippocampus and amygdala, in some dogs these conditions were the best in the theta and beta 2 ranges, in other animals--in the theta and alpha bands. In phlegmatic dogs, spectral densities in the theta range were higher in the left hippocampus than in the symmetrical structure, in sanguine animals spectral densities in the theta and beta 2 ranges in the hippocampus and amygdala were higher in the right hemisphere than in the left one. Thus, the hemispheric asymmetry of electrical activity of the limbic formations seems to be an important factor, which determines the individual typological features of the higher nervous activity in dogs.     

Serotonin reuptake blocker fluoxetine suppresses hippocampal theta oscillation in rabbits during EEG

In earlier studies it has been shown that stimulation of the median raphe nucleus (MR) in awake rabbits decreases the expression and frequency of oscillatory theta activity in the septohippocampal system, and the functional blockade of this nucleus evokes the regular and high-frequency theta rhythm. The present work was aimed at elucidation of serotoninergic influence of MR (which also contains cells of other chemical nature) to the septohippocampal system of theta activity. Serotonin reuptake blocker fluoxetine that increases brain serotonin level was applied. Hippocampal electroencephalogram was recorded in awake rabbits. Bilateral intracerebroventricular infusion of fluoxetine hydrochloride (Sigma, St. Louis; 15 micrograms in 5 microliters saline) in all cases reduced the rhythmic theta activity. In 15 of 18 (83.3%) of experiments the decrease in hippocampal theta oscillations was more than 50% of the control level. The theta band of the spectral density histogram decreased in the mean by 56 +/- 5.8% of the control level (from 10 to 93% in different experiments, p < 0.001). The mean latency of these changes was 3.5 +/- 0.11 minutes (2.9-4.1 min), the effect duration was 64 +/- 3.2 min (45.3-90 min). The mean frequency of the theta waves did not change as compared to the baseline and was equal to 5.25 +/- 0.5 Hz (4.5-6.5 Hz). The fluoxetine-induced reduction of the theta rhythm expression in hippocampus is the evidence of its inhibitory control by serotoninergic brain system. It is suggested that the increase of the frequency of hippocampal theta rhythm after the functional blockade of MR observed in our earlier experiments was the result of a release of the septohippocampal system from the influence of nonserotoninergic neurons (via glutamatergic reticular formation) and/or temporary cessation of the MR interaction with noradrenergic, dopaminergic and glutamate/aspartate systems.     

Effect of substance P on behavior in the rabbit and the activity of cortical neurons during training

Subcutaneous injection of substance P to rabbits in a dose of 250 mcg/kg elicited a transitory disappearance of motor reactions to painful reinforcing stimuli and a reduction of their probability to reinforced and inhibitory light flashes, as well as a protracted heart rate increase and decrease of respiration rate. One third of the neurones recorded decreased their background firing level and or excitatory components of the reactions to reinforcement and conditioned light flashes. The decrease was most distinctly seen in the sensorimotor cortex and less pronounced in the visual cortical area and hippocampus. The influence of the substance P on different types of cortical inhibition was not the same. Tonic inhibition of neuronal activity in response to reinforcement was enhanced. Bioelectrical parameters which reflect an enhancement of inhibitory hyperpolarization during elaboration of internal inhibition (i.e. inhibitory firing delays and corresponding background and evoked slow potentials oscillations) were not changed.