Searching activity under different reinforcement regimens and the process of information interaction with the environment]

When training rats in casual environmental conditions the search activity is determined by the regimen of unconditioned confirmation and the probability of a primary chance correct performance of instrumental reactions (PCCR). The value of PCCR determines what part of instrumental reactions will be realized due to a conditioned signal and confirmed appropriately. This, in its turn, influences the informational interaction of the animal with the environment in any regimen of confirmation (constant or probable). With the least favourable values of PCCR for learning a decreased number of confirmation lowers the search activity due to a sharp deterioration of the conditions for acquiring information--both factors (PCCR and low frequency of confirmation) cause single-directed changes (decrease) in informational significance of research reactions. The optimal PCCR values for learning promote informational significance of every search reaction, this leading to, weakening of the relationship between the intensity of the search activity and probability of unconditioned confirmation.     

Influence of the probability of the random performance of an acquired reaction on the rate of the formation of an instrumental reflex

Instrumental reflex formation in rats takes place more rapidly at high probability of random performance of instrumental reaction to light; however, it does not depend on the frequency of correct responses positive reinforcements (from 50 to 100%). In case of low probability, the learning process sharply slows down at 50% reinforcement of correct responses in comparison with 100% one.     

The dependence of the rate of learning on the probability of the random performance of an acquired reaction under different regimens of aversive reinforcement in rats

Learning of rats in the process of elaboration of instrumental conditioned reflex takes place much faster at the probability of random fulfillment of correct reaction (PRCR) equal to 0.25 and 0.125 than at PRCR 0.5 and 0.05. Decrease of the frequency of positive reinforcements of correct reactions from 100 to 25% does not influence the speed of learning at PRCR 0.25 and 0.125, however significantly retards the process of learning at PRCR 0.05. There exist optimum and pessimum for learning PRCR values at different regimes of reinforcement.     

Activity of neurons of the motor zone of the cortex during elaboration of a local instrumental defensive reflex in the rabbit

During instrumental defensive reaction of wrist extension in response to a sound (conditioned) stimulus, two types of neuronal responses in the rabbit motor cortex were discovered. The first type was recorded in cells with activity not connected with electromyographic activity of wrist extensors. The reaction consisted in the appearance of inhibitory response at the place of the cancelled electrocutaneous stimulation at animal's performance of conditioned reaction to sound. The second type of responses was shown for a neurone with the activity significantly related to electromyographic activity. In this case the conditioned motor response was accompanied by enhancement of the cellular activation reaction to sound and the increase of spike activity in interstimuli intervals.     

Emotional stress during conditioned reflex transformation of heterogeneous instrumental reflexes

The factors leading to pronounced emotional stress accompanied by changes in electrical activity of hippocampus were studied in four dogs during elaboration of conditioned switching-over of heterogeneous instrumental reflexes. Objectively recorded signs of emotional stress were observed in two cases: when the animal was not accurate enough in discerning defensive and alimentary situations and throughout the improvement of instrumental defensive reflex. Pronouncement of hippocampal theta-rhythm increased at those stages of switching-over elaboration where the probability of successful avoiding pain stimulation was relatively low. The data obtained permit the conclussion that theta-rhythm is the correlate of the degree of the emotional stress and not only a manifestation of general arousal reaction depending on the level of sensory input.     

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.     

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.     

Tonic component of the conditioned reflex process and its functional role

Tonic background activity of 266 neurones in the hippocampus and different neocortical areas was studied in freely moving rabbits in the process of defensive and food instrumental conditioned performance and during switching-over of instrumental and classical food and defensive reflexes. Associations of CS and reinforcement evoke background activity changes in most of recorded cortical neurones preceding the development of other conditioned manifestations. Conditioned reflex was performed only after reaching the background firing rate of almost every examined neurone optimal for its realization. The performance of different conditioned reflexes was associated with different background activity levels of cortical neurones. The above mentioned data form the experimental basis for the identification of the tonic component in conditioned process which reflects tonic character of temporary connection formation and function.     

骤冷与饥饿对小鼠肝脏影响的实验研究

为探讨饥饿及饥饿与骤冷对动物肝脏的影响,本实验用健康昆明种小鼠２５只,随机分成正常组５只,饥饿组１０只,饥饿后再予冷刺激组１０只（下称骤冷组）。采用组织化学及酶组织化学方法观察糖原（ＰＡＳ反应）、ＳＤＨ（琥珀酸脱氢酶）,ＬＤＨ（乳酸脱氢酶）,ＣｈＥ（胆碱酯酶）、Ｍｇ２＋－ＡＴＰａｓｅ（镁激活三磷酸腺苷酶）,ＡＣＰ（酸性磷酸酶）。结果提示：饥饿时肝脏ＰＡＳ反应,ＳＤＨ,Ｍｇ２＋－ＡＴＰａｓｅ、ＣｈＥ活性显著下降,而ＡＣＰ活性明显增强;饥饿后骤冷时ＰＡＳ（反应）、ＳＤＨ、ＣｈＥ更显著下降,而ＡＣＰ及Ｍｇ２＋－ＡＴＰａｓｅ活性反而增强。     

Characteristics of the response of sensomotor cortex neurons of the cat during performance of rapid purposeful movements

Neuronal activity of cat sensorimotor cortical area was studied during performance of movements of grasping a visual goal appearing for a short time. Characteristics and the pattern of neuronal discharge became stabilized in the process of animal training and did not depend on the time of goal presentation, absence or presence of the reinforcement under preservation of animal's motor reaction. Changes in responses were observed in situations of uncertainty: at 50% of reinforcement probability and (or) at successful performance of the motor reaction in half of cases.     

Mutagen formed from tryptophan reacted with sodium nitrite in acidic solution

The reaction products from L-tryptophan treated with nitrite under acidic conditions were investigated for mutagenic activity with the Salmonella typhimurium his reversion assay and for DNA-damaging activity using the rec-assay. The diethyl ether extract of the reaction mixture showed 8 spots on thin-layer chromatography (TLC). One compound from the TLC had high mutagenic activity for TA98 without S9 mix, with little DNA-damaging activity. The mutagen was purified and identified by instrumental analysis as 2-hydroxy-(1-N-nitrosoindole)propionic acid (NIHP). The mutagenic activity of NIHP was determined by the induced mutation frequency method; the induced mutation frequency was about 19.2 X 10(-5) at a dose level of 160 micrograms/plate.     

MyriMatch: highly accurate tandem mass spectral peptide identification by multivariate hypergeometric analysis

Shotgun proteomics experiments are dependent upon database search engines to identify peptides from tandem mass spectra. Many of these algorithms score potential identifications by evaluating the number of fragment ions matched between each peptide sequence and an observed spectrum. These systems, however, generally do not distinguish between matching an intense peak and matching a minor peak. We have developed a statistical model to score peptide matches that is based upon the multivariate hypergeometric distribution. This scorer, part of the "MyriMatch" database search engine, places greater emphasis on matching intense peaks. The probability that the best match for each spectrum has occurred by random chance can be employed to separate correct matches from random ones. We evaluated this software on data sets from three different laboratories employing three different ion trap instruments. Employing a novel system for testing discrimination, we demonstrate that stratifying peaks into multiple intensity classes improves the discrimination of scoring. We compare MyriMatch results to those of Sequest and X!Tandem, revealing that it is capable of higher discrimination than either of these algorithms. When minimal peak filtering is employed, performance plummets for a scoring model that does not stratify matched peaks by intensity. On the other hand, we find that MyriMatch discrimination improves as more peaks are retained in each spectrum. MyriMatch also scales well to tandem mass spectra from high-resolution mass analyzers. These findings may indicate limitations for existing database search scorers that count matched peaks without differentiating them by intensity. This software and source code is available under Mozilla Public License at this URL: http://www.mc.vanderbilt.edu/msrc/bioinformatics/.     

Effect of pentobarbital on the biothermic individuality of growing rats and during instrumental conditioning in heat]

At the dosis of 12,5 mg by kg and in 30 growing white rats, pentobarbital acts by shortening the reaction time, by inducing a short period of psychomotor instrumental activity and after a latency of 5 to 20 mn by depressing the total reserve of instrumental activity acquired before this sessions under physiological serum or caffein injections state dependent larning in heat.     

Robust biased Brownian dynamics for rate constant calculation

A reaction probability is required to calculate the rate constant of a diffusion-dominated reaction. Due to the complicated geometry and potentially high dimension of the reaction probability problem, it is usually solved by a Brownian dynamics simulation, also known as a random walk or path integral method, instead of solving the equivalent partial differential equation by a discretization method. Building on earlier work, this article completes the development of a robust importance sampling algorithm for Brownian dynamics-i.e., biased Brownian dynamics with weight control-to overcome the high energy and entropy barriers in biomolecular association reactions. The biased Brownian dynamics steers sampling by a bias force, and the weight control algorithm controls sampling by a target weight. This algorithm is optimal if the bias force and the target weight are constructed from the solution of the reaction probability problem. In reality, an approximate reaction probability has to be used to construct the bias force and the target weight. Thus, the performance of the algorithm depends on the quality of the approximation. Given here is a method to calculate a good approximation, which is based on the selection of a reaction coordinate and the variational formulation of the reaction probability problem. The numerically approximated reaction probability is shown by computer experiments to give a factor-of-two speedup over the use of a purely heuristic approximation. Also, the fully developed method is compared to unbiased Brownian dynamics. The tests for human superoxide dismutase, Escherichia coli superoxide dismutase, and antisweetener antibody NC6.8, show speedups of 17, 35, and 39, respectively. The test for reactions between two model proteins with orientations shows speedups of 2578 for one set of configurations and 3341 for another set of configurations.     

Conditioned posture changes in dogs after systemic administration of dopaminergic agents

Influence of systemic injection of some dopaminergic drugs on conditioned postural rearrangement prior to instrumental movement realization and on other motor components of instrumental reaction as well as on the performance of the instrumental task itself--was studied in chronic experiments in 5 dogs on a model of instrumental defensive reflexes connected with maintenance of a certain posture. Drugs were used influencing the nigrostriate dopaminergic system, i.e. dopamine agonist L-DOPA and haloperidol blocking dopamine striate receptors. All the motor components of the instrumental reaction and first of all conditioned postural rearrangement were modified by systemic haloperidol injection. Initial components of the postural rearrangement were modified to the greatest extent, in particular the period of preparation of the animal to the posture change increased. On the contrary, the latency of initiation of postural rearrangement was sharply shortened by systemic injection of L-DOPA. On the other hand, the main component of the postural change, i.e. redistribution of body mass among the bearing limbs (the values of which significantly increased after preliminary stimulation of the head of the caudate nucleus) changed insignificantly during modulation of the striatum dopamine level.     

Effects of L-dopa during Auditory Instrumental Learning in Humans

The dopaminergic neurotransmitter system is critically involved in promoting plasticity in auditory cortex. We combined functional magnetic resonance imaging (fMRI) and a pharmacological manipulation to investigate dopaminergic modulation of neural activity in auditory cortex during instrumental learning. Volunteers either received 100 mg L-dopa (Madopar) or placebo in an appetitive, differential instrumental conditioning paradigm, which involved learning that a specific category of frequency modulated tones predicts a monetary reward when fast responses were made in a subsequent reaction time task. The other category of frequency modulated tones was not related to a reward. Our behavioral data provides evidence that dopaminergic stimulation differentially impacts on the speed of instrumental responding in rewarded and unrewarded trials. L-dopa increased neural BOLD activity in left auditory cortex to tones in rewarded and unrewarded trials. This increase was related to plasma L-dopa levels and learning rate. Our data thus provides evidence for dopaminergic modulation of neural activity in auditory cortex, which occurs for both auditory stimuli related to a later reward and those not related to a reward.     

Modelling eye movements in a categorical search task

We introduce a model of eye movements during categorical search, the task of finding and recognizing categorically defined targets. It extends a previous model of eye movements during search (target acquisition model, TAM) by using distances from an support vector machine classification boundary to create probability maps indicating pixel-by-pixel evidence for the target category in search images. Other additions include functionality enabling target-absent searches, and a fixation-based blurring of the search images now based on a mapping between visual and collicular space. We tested this model on images from a previously conducted variable set-size (6/13/20) present/absent search experiment where participants searched for categorically defined teddy bear targets among random category distractors. The model not only captured target-present/absent set-size effects, but also accurately predicted for all conditions the numbers of fixations made prior to search judgements. It also predicted the percentages of first eye movements during search landing on targets, a conservative measure of search guidance. Effects of set size on false negative and false positive errors were also captured, but error rates in general were overestimated. We conclude that visual features discriminating a target category from non-targets can be learned and used to guide eye movements during categorical search.     

Photoreactions of the littoral trematode Renicola thaidus (Trematoda: Renicolida)

The behavioral response of Renicola thaidus cercariae (Renicolidae) to the light has been studied. The positive photo reaction was observed during the first hour of the cercariae free-living period (after shedding from the mollusc). Six hour old cercariae did not show any direct photo reaction. Temporal presence of the positive photo reaction promotes a wider spatial distribution of R. thaidus cercariae. This fact may increases a probability of successful finding and infection of the second intermediate host--bivalves such as the blue mussels. Besides, the more random distribution of infection in bivalve host populations is achieved. This circumstance increases a probability of infected bivalve to be eaten by the final hosts--seabirds.     

The role of muscarinic cholinoreceptors in the retrieval of the instrumental food conditioned reflex in cats

It was demonstrated in cat experiments that impairment of the retrieval of appetitive instrumental conditioning observed after systemic administration of antagonists of muscarinic central cholinoreceptors scopolamine (a nonselective M1 antagonist) and trihexyphenidyl (relatively selective M1 antagonist) could be connected with central and peripheral side effects of these antagonists. It was established that in case of the absence of side effects (low doses of trihexyphenidyl, 1 mg/kg) the blockade of M1-cholinoreceptors led either to selective fall-off of the motor instrumental reaction with in the presence of contextual behavior and other conditioned reactions or the appearance of errors that seemingly was indicative of the disturbance of triggering and realization of the motor program as the most important component of conditioning performance. The systemic injection of trihexyphenidyl (10 mg/kg), scopolamine (0.03 and 0.06 mg/kg) and nonselective peripheral antagonist methylscopolamine (0.03 mg/kg) led to changes in the general functional state (disorders in the emotional and motivational sphere), the expression of which depended on the individual sensitivity to anticholinergic drugs. The disturbance of CR retrieval observed in parallel with side reactions was characterized by a complete cessation of conditioning and apparently was not associated with memory deterioration.     

Orientation of Aplysia californien to distant food sources

Summary The behavior of the marine mollusc Aplysia was examined under different experimental conditions designed to determine the food searching strategy of the animals. In a small, open field tank with still water, the animals took an average of 42 min to find a piece of seaweed, even though the stimulus was never located more than 30 cm away from the animal. Observations of the animals indicated that their search was not directed, without a clear tendency towards the food, and during the course of a search, they often crawled through most of the area of the tank. The search time, the distance travelled, and the strategy of the search of the animals was similar for different types of seaweed. If animals were aroused into activity by the presence of seaweed extract, the time for them to contact a piece of odorless glass fiber paper in the open field was not significantly different than that for a piece of seaweed. The probability at which the animals contacted the seaweed, as a function of the distance travelled, resembled the detection probability determined according to a theory of random search. We thus propose that the aroused animals move in a random pattern until they are very close to the food. This strategy can be advantageous in still water since chemicals do not provide distinct gradients that can serve as cues for chemotactic orientation from distances greater than a few centimeters from the source.In a Y-maze in still water, Aplysia did not perform above chance in selecting the arm that contained the seaweed. In streaming water, the animals entered the arm that contained seaweed significantly above chance only if a large piece of seaweed was used, so as to provide a very strong stimulus. Similarly, presentation of a high concentration of glutamate or a high concentration of seaweed extract to one side of the animal could evoke turning towards the stimulus. In the Y-maze, animals that repeatedly entered and exited both arms before making a choice, performed better than those that went directly into one arm.We conclude that chemical food stimuli can evoke directed orientation only when the animal is very close to the stimulus (within a few centimeters, at most). For Aplysia, the role of distant chemical stimuli may not be to guide their orientation, but rather to evoke the food-induced arousal state. In this behavioral state, several behaviors, such as locomotion are altered, and these changes may provide the basis for locating food from a distance.Abbreviation SWE seaweed extract