Shifts in steady potential levels and changes in the cerebral bioelectrochemical potential during orientation and conditioned reflexes in rabbits]

The shifts of the steady potential level (SPL), recorded with non-polarized electrodes, and the changes in bioelectrochemical potential (BEChPs), recorded with platinum electrodes, were led from the rabbit brain surface in chronic experiments. The stimuli, that were new for the animal, caused only SPL shifts (0.1-0.3 mv), BEChPs showing no changes. BEChPs changed (by tenths to several millivolts) only in the process of the conditioned reflex formation, during the pairing of the conditioned and reinforcing stimuli, during which the shifts of SPL were also observed (up to 0.5-1 mv), different from the ones during the orienting reflex. Simultaneous recording of the SPL shifts and the changes in BEChPs showed that these phenomena are external manifestations of independent processes. It is suggested that the brain activity involved in the perception and the analysis of the informational value of a new stimulus, is connected with bioelectrical processes, rather than with the metabolic ones. During the formation of the defensive conditioned reflex, along with the enhancing of the activity connected with bioelectrical processes, other type of activity appears which is accompanied with considerable metabolic shifts.     

Changes in trace reactions of sensorimotor cortex and putamen neurons as affected by haloperidol

Experiments on conscious rabbits were made to elaborate motor conditioned reflexes through pairing stimuli with electrocutaneous reinforcement applied every 30 s. Neuronal activity in the sensorimotor cortex and putamen was recorded during formation and reproduction of the conditioned reflexes before and after haloperidol injection (0.2 mg/kg i. v.). In the putamen, haloperidol increased the number of neurons exhibiting trace conditioned activity and made the intensity and duration of these processes rise. The changes seen in the sensorimotor cortex were opposite in nature. Inhibition of trace conditioned activity in the sensorimotor cortex depended mainly on the decreased amplitude of the reaction conditioned component. The role of the dopaminergic system in the interaction of the neostriatum and sensorimotor cortex and in formation and reproduction of trace conditioned activity of both the structures is discussed.     

Neuronal activity of the cerebral cortex in cats with conditioned inhibition

Unit activity of the somatosensory cortex was studied in chronic experiments on cats during alimentary instrumental conditioned reflex performance and elaboration of conditioned inhibition (CI). First presentations of the CI signal at the beginning of CI formation caused, due to orienting reaction to a new stimulus, a levelling of the response of the neurones to the positive conditioned signal included into the CI complex. At the stage of consolidated CI, this depression proceeded gradually during the development of conditioned inhibition caused by consecutive presentations of the nonreinforced CI combination. Two groups of neurones were involved in the process of the CI performance: one of them being the same which was activated also in response to positive stimulation during performance of the conditioned response, and the second one being areactive to the positive conditioned stimulus but reducing the frequency of the background activity.     

Ontogenetic characteristics of the acquisition and extinction of a taste aversion in dogs following damage to the dorsal area of the hippocampus

In 2-9 months dogs the influence was studied of ablation of the hippocampus dorsal area on formation and preservation of conditioned taste aversion (CTA), elaborated by combination of 30% sucrose solution with i.p. injection of 0.28 M LiCl solution. Lesion of the hippocampus dorsal area does not prevent acquisition after the first pairing of conditioned taste aversion in puppies and adult dogs. Heterogeneous influences are observed after hippocampus lesions on the process of CTA extinction in animals of different ages. Acquaintance with conditioned stimulus before CTA acquisition accelerates the process of its extinction in hippocampectomized indiviuals, but less than in animals with an intact hippocampus.     

Orienting reflex: "targeting reaction" and "searchlight of attention"

The concept of orienting reflex based on the principle of vector coding of cognitive and executive processes is proposed. The orienting reflex to non-signal and signal stimuli is a set of orienting reactions: motor, autonomic, neuronal, and subjective emphasizing new and significant stimuli. Two basic mechanisms can be identified within the orienting reflex: a "targeting reaction" and a "searchlight of attention". In the visual system the first one consists in a foveation of a target stimulus. The foveation is performed with participation of premotor neurons excited by saccadic command neurons of the superior colliculi. The "searchlight of attention" is based on the resonance of gamma-oscillations in the reticular thalamus selectively enhancing responses of cortical neurons (involuntary attention). The novelty signal is generated in novelty neurons of the hippocampus, which are selectively tuned to a repeatedly presented standard stimulus. The selective tuning is caused by the depression of plastic synapses representing a "neuronal model" of the standard stimulus. A mismatch of the novel stimulus with the established neuronal model gives rise to a "novelty signal" enhancing the novel input. The novelty signal inhibits current conditioned reflexes (external inhibition) contributing to redirecting the behavior. By triggering the expression of early genes the novelty signal initiates the formation of the long-term memory connected with neoneurogenesis.     

Conditioning and time representation in long short-term memory networks

Dopaminergic models based on the temporal-difference learning algorithm usually do not differentiate trace from delay conditioning. Instead, they use a fixed temporal representation of elapsed time since conditioned stimulus onset. Recently, a new model was proposed in which timing is learned within a long short-term memory (LSTM) artificial neural network representing the cerebral cortex (Rivest et al. in J Comput Neurosci 28(1):107–130, 2010). In this paper, that model’s ability to reproduce and explain relevant data, as well as its ability to make interesting new predictions, are evaluated. The model reveals a strikingly different temporal representation between trace and delay conditioning since trace conditioning requires working memory to remember the past conditioned stimulus while delay conditioning does not. On the other hand, the model predicts no important difference in DA responses between those two conditions when trained on one conditioning paradigm and tested on the other. The model predicts that in trace conditioning, animal timing starts with the conditioned stimulus offset as opposed to its onset. In classical conditioning, it predicts that if the conditioned stimulus does not disappear after the reward, the animal may expect a second reward. Finally, the last simulation reveals that the buildup of activity of some units in the networks can adapt to new delays by adjusting their rate of integration. Most importantly, the paper shows that it is possible, with the proposed architecture, to acquire discharge patterns similar to those observed in dopaminergic neurons and in the cerebral cortex on those tasks simply by minimizing a predictive cost function.     

Properties of olfactory conditioning in the housefly, Musca domestica

The housefly, Musca domestica, was conditioned to odours using the proboscis extension response to labellar stimulation with sucrose solution as an unconditioned response and the properties of conditioning were investigated. Among trials including forward pairing of the conditioned stimulus (CS) with the unconditioned stimulus (US), backward pairing and isolated presentations of CS and US, only forward pairing is effective on the acquisition of conditioning. Backward pairing combined with forward pairing does not influence the effectiveness of the forward pairing. CS given overlapping with a US presentation permits only weak conditioning. The acquisition of conditioning decreases with increase of the CS-US interval. In the differential conditioning situation to two odours, discriminative responses are observed. In the flies conditioned with one antenna, the conditioned response is elicited not only by stimulation of the antenna used for conditioning but also by stimulation of the antenna not used for conditioning, although the response using the former is higher than with the latter. The ability to be conditioned is reduced immediately after fastening on a clay bed and increases with time. Ability can also be improved by transection of the ventral nerve cord.     

Molecular Signals into the Insular Cortex and Amygdala During Aversive Gustatory Memory Formation

In this paper, we will provide evidence of the putative molecular signals and biochemical events that mediate the formation of long-lasting gustatory memory trace. When an animal drinks a novel taste (the conditioned stimulus; CS) and it is later associated with malaise (unconditioned stimulus; US), the animal will reject it in the next presentation, developing a long-lasting taste aversion, i.e., the taste cue becomes an aversive signal, and this is referred to as conditioning taste aversion. Different evidence indicates that the novel stimulus (taste) induces a rapid and strong cortical acetylcholine activity that decreases when the stimulus becomes familiar after several presentations. Cholinergic activation via muscarinic receptors initiates a series of intracellular events leading to plastic changes that could be related to short- and/or long-term memory gustatory trace. Such plastic changes facilitate the incoming US signals carried out by, in part, the glutamate release induced by the US. Altogether, these events could produce the cellular changes related to the switch from safe to aversive taste memory trace. A proposed working model to explain the biochemical sequence of signals during taste memory formation will be discussed.     

Spectral correlation parameters of neocortical potentials in the rabbit undergoing paired isorhythmic stimulation

At pairing of isorhythmic stimuli beyond the theta-rhythm frequency limits (3 and 8 Hz), in power spectra of EEGs of the sensorimotor and visual neocortical areas of rabbits, the frequencies are present both of the theta-range and of the stimulation frequency, in the background activity as well as during the stimulation. Both rhythms are in reciprocal relations. The frequency of the theta-rhythm approaches the frequency divisible by that of the stimulation. Under the action of the conditioned stimulus, crosscorrelation coefficients (CC) between the potentials of the areas under study decrease in most cases in comparison to their background values. Combination of the conditioned stimulus with the unconditioned one, leads approximately in equal number of cases to an increase or decrease of CC. After elimination of the stimuli, in most cases CC increases. CC of the background activity does not increase in the course of paired stimuli presentation though a conditioned response is being formed. At presence of stimuli frequency fluctuations simultaneously in the potentials of both areas, the rise of coherence function at this frequency does not occurs always. Thus, the above spectral-correlation parameters of rabbit's cortical potentials differ from those which arise at pairing of continuous nonrhythmic stimuli. This difference is probably due to different characteristics of the stimuli presented.     

Hippocampal place cells acquire location-specific responses to the conditioned stimulus during auditory fear conditioning

We recorded neurons from the hippocampus of freely behaving rats during an auditory fear conditioning task. Rats received either paired or unpaired presentations of an auditory conditioned stimulus (CS) and an electric shock unconditioned stimulus (US). Hippocampal neurons (place and theta cells) acquired responses to the auditory CS in the paired but not in the unpaired group. After CS-US pairing, rhythmic firing of theta cells became synchronized to the onset of the CS. Conditioned responses of place cells were gated by their location-specific firing, so that after CS-US pairing, place cells responded to the CS only when the rat was within the cell's place field. These findings may help to elucidate how the hippocampus contributes to context-specific memory formation during associative learning.     

Appetitive and aversive learning in Spodoptera littoralis larvae

Adult Lepidoptera are capable of associative learning. This helps them to forage flowers or to find suitable oviposition sites. Larval learning has never been seriously considered because they have limited foraging capabilities and usually depend on adults as concerns their food choices. We tested if Spodoptera littoralis larvae can learn to associate an odor with a tastant using a new classical conditioning paradigm. Groups of larvae were exposed to an unconditioned stimulus (US: fructose or quinine mixed with agar) paired with a conditioned stimulus (CS: hexanol, geraniol or pentyl acetate) in a petri dish. Their reaction to CS was subsequently tested in a petri dish at different time intervals after conditioning. Trained larvae showed a significant preference or avoidance to CS when paired with US depending on the reinforcer used. The training was more efficient when larvae were given a choice between an area where CS-US was paired and an area with no CS (or another odor). In these conditions, the memory formed could be recalled at least 24 h after pairing with an aversive stimulus and only 5 min after pairing with an appetitive stimulus. This learning was specific to CS because trained larvae were able to discriminate CS from another odor that was present during the training but unrewarded. These results suggest that Lepidoptera larvae exhibit more behavioral plasticity than previously appreciated.     

Functional differentiation of the theta-rhythm of the hippocampus in the cat

On the model of discriminating alimentary conditioned reflex with spatial separation of the sources of conditioned (CR, light flashes) and unconditioned (feeding trough) stimuli the theta-rhythm of the dorsal hippocampus was evaluated in cats. Two types of the theta-rhythm were observed in the spectrum of the hippocampal electrical activity: low-amplitude, consisting of a slow growing theta-waves (type I) and high-amplitude consisting of rapidly increasing theta-waves (type II). The type I theta-rhythm is sensitive to noradrenaline and correlates with behavioural forms directed immediately to the realization of alimentary motivation, while the type II is sensitive to serotonin and correlates with behavioural forms directed to the source of the conditioned stimulus. Enhancement of the type II theta-rhythm takes place during a delay of the expected conditioned stimulus. It is suggested that type I theta-rhythm reflects a level of activity of the brain structures connected with unconditioned mechanisms, with realization of biological motivations, while type II theta-rhythm is connected with conditioned reinforcing stimuli; it correlates with various forms of conditioned orienting reflexes and reflects the work of the "nervous model of reinforcing stimulus".     

Effects of vertical prey distribution on the food-searching behaviour of Danube bleak Chalcalburnus chalcoides mento

Planktivorous fishes frequently have to cope with spatial dynamics of their prey and should be flexible in their vertical food search position. In two experiments Danube bleak Chalcalburnus chalcoides mento, a planktivorous cyprinid, was conditioned to forage on chironomid larvae within the bottom zone and on the cladoceran Leptodora kindtii in the open water of experimental tanks. The fish responded to the presence of chironomids by orienting their snapping behaviour towards the bottom. After most of the prey were depleted, the fish shifted their search position to the open water. Fish were offered L. kindtii at higher densities than the chironomids in the second experiment. With one exception all fish snapped at a high rate into the open water with no observed vertical spatial shifts. One highly active individual showed a clear shift from the open water towards the bottom after depleting most of the L. kindtii. After previous conditioning with chironomids, Danube bleak responded to the presentation of a conditioned stimulus by searching at a deeper position than during control recordings of spontaneous snappings and during a conditioned response test after training with L. kindtii. These results provide preliminary evidence that Danube bleak can detect variation in vertical prey distribution and can build up internal spatial representations.     

Spontaneous activity of hippocampal neurons and stimulation rhythm acquisition in young rabbits during learning: age features

Ontogenetic mechanisms of memory formation were studied using an experimental model of conditioned reflex to time, i.e., trace acquisition of a stimulation rhythm by hippocampal CA1 neurons of young (1-4 weeks old) and adult rabbits (5-6 months old). It was found that age-related development of learning ability includes several stages: complete absence of memory traces (6-7 days old), rapid acquisition without consolidation (8-14 days old), and formation of perfect memory (25-30 days old). Both specific and nonspecific changes in spontaneous activity of neurons were observed. Changes in the rate of discharges related to rhythmic stimulation were accompanied by changes in spontaneous activity. With the development of an animal, spike activity increased in parallel with improving of the functional properties of neurons, their structural organization, formation of the afferent contacts in the hippocampus completed after a period of three weeks from birth, and formation of metabolic processes, modulatory systems, and traffic function of hippocampal neurons. A capability for plastic reorganization is of great importance for adaptation mechanisms and conditioned behavior of a developing animal in accordance with structural maturation and development of the functional regulation of neuronal reactivity in the hippocampus.     

Operant conditioning of brain steady potential shifts in man.

Steady potential shifts (SPS) recorded from the scalp were conditioned operantly by visual and acoustical feedback. Three groups of seven subjects were each tested with a different response-reinforcement contingency: positive reinforcement for a positive SPS after a cue stimulus, positive reinforcement for a negative SPS after a cue stimulus, and noncontingent reinforcement. The steady potential shifts learned under these three conditions differed significantly. Negative shifts were associated with subjective feelings of activation, positive shifts with inactivation. Cortical genesis and possible artifacts are discussed.     

Conditioned augmentation of natural killer cell activity. Independence from nociceptive effects and dependence on interferon-beta

Injection of mice with 20 micrograms polyinosinic: polycytidylic acid (Poly I:C) after exposure to camphor odor results in a conditioned augmentation of natural killer cell (NK) activity. In this study, we show that the conditioned response is not the result of nociceptive stimulation and that interferon-beta (IFN), but not IFN-alpha can replace Poly I:C as the unconditioned stimulus (US). Two conditioned stimuli (CS) were used with equivalent results. A combination CS consisting of a novel taste (saccharin) and a 125 mg/kg injection of LiCl that induces gastric upset was paired with a Poly I:C or IFN-beta (1 X 10(4) IU) injection. This resulted in an augmentation of NK activity when the conditioned animals were reexposed to the saccharin-LiCl CS. In addition, an identical conditioned response was elicited when a camphor odor CS was paired with either of these US. To test whether the conditioned response might be an artifact not detected by our controls, a mock conditioning experiment was performed, which assessed the differential effect of multiple exposures to the saccharin-LiCl CS without a CS/US pairing. The mock conditioned group was significantly suppressed relative to saline treated controls, whereas the mock nonconditioned group and the mock conditioned group that was not reexposed to the CS after conditioning did not show significant suppression. This indicates that the augmentation observed in the conditioned group after CS/US pairing was not the result of exposure to the CS itself. Small doses of Poly I:C (5 micrograms or 2.5 micrograms) given on days 3 and 5 (or on day 5 only) to boost NK activity had the effect of increasing the magnitude of the conditioned response measured on day 6. In addition, an identical conditioned response was observed when the interval between the CS/US pairing and the later CS exposures was changed, which places the test for the conditioned response either on day 6 (CS given on days 3 and 5) or day 10 (CS given on days 7 and 9). These results show that the observed conditioned enhancement of NK activity in conditioned animals is not caused by any nociceptive properties of the CS itself and is dependent on the IFN-beta produced after Poly I:C injection in the conditioned paradigm.     

The Specificity Of Processes Of Motivational Conditioning In The Human Mind

The methodological principle of the objectification of needs, which in activity theory explains the ontological development of motivation (Leont'ev, 1975), is in need of concrete psychological development to ascertain what influences and mental processes give rise to such objectification. In terms of biological motivation, this question is made easier by the existence of a detailed system of data, accumulated in conditioning studies, concerning the acquisition of the capacity to activate a person by neutral stimuli. A psychological interpretation of these data purports to explain the fact that the conditioned response phenomenon indicates not only a redirecting of unconditioned responses toward new stimuli but also the genesis, in response to this stimulus, of subjective relations orienting the person toward influences relevant to his needs. Such an interpretation therefore helps to concretize the concept of the objectification of biological needs (Vilyunas, 1986. Pp. 154-74).     

Acquisition and extinction of conditioned suppression of a graft-vs-host response in the rat

Injection of rats with cyclophosphamide (CY) after their consumption of a novel saccharin-flavored drinking solution results in a conditioned aversion to saccharin and a conditioned suppression of immune responses. In this study, female Lewis X Brown Norwegian F1 rats were conditioned by pairing saccharin with 50 mg/kg CY. Seven weeks later (day 0), a graft-vs-host response (GvHR) was induced in these animals by injecting splenic leukocytes from Lewis donors into a rear footpad. At this time, some conditioned animals were reexposed to saccharin, the conditioned stimulus. During the 7-wk interval between conditioning and immunization, subgroups of conditioned rats were given 0, 4, 9, or 18 extinction trials (saccharin followed by saline injections). Animals receiving 4, 9, or 18 extinction trials showed a greater preference for saccharin on day 0 than did animals receiving no extinction trials, but these groups did not differ among themselves; all conditioned groups showed a lower preference for saccharin than placebo-treated animals. There was a clear effect of number of extinction trials on the GvHR. Animals receiving 9 or 18 extinction trials did not differ from controls, whereas animals receiving 0 or 4 trials had a milder GvHR than did conditioned rats that were not reexposed to saccharin at the time of immunization. These results confirm a previous report of conditioned suppression of a GvHR, demonstrate that conditioned immunopharmacologic responses are subject to experimental extinction, and indicate that conditioned immunosuppression can be dissociated from conditioned taste aversion.     

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.     

Analysis of the spatial-temporal EEG organization as the way to the knowledge of neurophysiological mechanisms of the integrative brain activity

Short results' review of investigations of Laboratory of Neurophysiology of Child of Sechenov Institute is presented in the article. Investigations are based on concept of academic M.N. Livanov about special role of spatial-temporal relations of brain potentials oscillations of various brain areas in providing of functional connection between them. It is shown, that in rest condition the structure of interregional relations of cortex biopotentials in all healthy people is characterized by high spatial orderliness that obviously assists to optimal realization of informational processes during various functional conditions from rest to complex cognitive functions. Special attention is given for the problem of functional signigicance of phase shifts of EEG waves. Data, that allows concluding that brainstem and thalamocartical integrative systems are characterized with relatively small inherited and phenotypic variability whereas fiber systems of both hemispheres that provide processes of intercortical integration are characterized by more expressed inter-individual variability, is presented. Intensive development of long associative and commissural tracks of telencephalon that joined even the most distanced cortical regions of hemispheres in united formation apparently results in formation of morpho-functional "skeleton" of neocortex, that occurred to be the basis for origin of qualitatively new (in comparison to animals) principals of formation of system organization of integral activity of the brain. Existence of long mono- and oligo-synaptic connections provides conditions for correlative develoment in ontogenesis of new function that is not conditioned by phylogenetic development.