Concomitant Pavlovian conditioning of heart rate and leg flexion responses in the rat

Pavlovian conditioning was studied in male Fischer 344 rats using tones as the conditioned stimulus (CS) and footshock as the unconditioned stimulus (UCS). Different groups of animals received (a) contiguous CS-UCS pairings with a 0.5 sec CS, (b) contiguous CS-UCS pairings with a 4.0 sec CS, or (c) a random sequence of noncontiguous tones and shocks using either a 0.5 sec or a 4.0 sec CS. Heart rate (HR) and leg flexion (LF) responses were recorded. Leg flexion conditioning occurred only in the 0.5 sec contiguous group. Decelerative HR CRs occurred only in the 4.0 sec contiguous group. Accelerative HR changes occurred in the other two groups but were significantly greater in the 0.5 sec contiguous group. These results are similar to but not identical to those obtained during eyeblink or nictitating membrane conditioning in rabbits, and suggest that the topography of the Pavlovian HR CR is dependent on the simultaneous occurrence of other classically conditioned responses.     

A pitfall for the expectancy theory of human eyelid conditioning

Two simple eyeblink conditioning experiments with random intermittent reinforcement schedules were performed. In Experiment 1, subjects had to rate their expectancy for an unconditioned stimulus (US) on a seven-level scale prior to each trial. As anticipated, expectancy for US increased with a successive conditioned stimulus (CS) alone, and decreased with successive CS-US pairings. However, Experiments 1 and 2 showed that the frequency of eyeblink conditioned responses (CRs) evolved in a direction opposite to that of expectancy changes: CRs increased, whereas expectancy for US decreased, and vice versa. The possible effect of sensitization on eyeblink response was ruled out by the lack of a run effect in an unpaired control group in Experiment 2. These results tend to disconfirm the expectancy theory of conditioning. Although they were explicitly predicted by the conventional "strength" theory of conditioning, an alternative interpretation is proposed within a cognitive framework.     

Reinstatement of short-latency responses after asymptotic Pavlovian conditioning training by the presentation of an extraneous stimulus

The purpose of this study was to examine whether the progressive disappearance of short-latency conditioned responses, or inhibition of delay, observed in Pavlovian conditioning with long inter-stimulus intervals, could be reverted by the presentation of a novel stimulus. In one experiment, two groups of rabbits received extensive training with a short (250 ms) or a long (1500 ms) tone that overlapped and terminated with a periorbital shock unconditioned stimulus. After training, the presentation of an extraneous stimulus prior to tone onset produced a reinstatement of short latency CRs in the group trained with the long CS, but did not affect CR latency in the group trained with the short CS. This finding is consistent with Pavlov's (1927) view that conditioning with long conditioned stimuli involves the acquisition of response tendencies in the early portion of the stimulus that are subsequently suppressed by the development of an inhibitory process.     

Pavlovian Conditioned Approach Training in Rats

Cues that are contingently paired with unconditioned, rewarding stimuli can acquire rewarding properties themselves through a process known as the attribution of incentive salience, or the transformation of neutral stimuli into attractive, "wanted'' stimuli capable of motivating behavior. Pavlovian conditioned approach (PCA) develops after the response-independent presentation of a conditioned stimulus (CS; e.g., a lever) that predicts the delivery of an unconditioned stimulus (US; e.g., a food pellet) and can be used to measure incentive salience. During training, three patterns of conditioned responses (CRs) can develop: sign-tracking behavior (CS-directed CR), goal-tracking behavior (US-directed CR), and an intermediate response (both CRs). Sign-trackers attribute incentive salience to reward-related cues and are more vulnerable to cue-induced reinstatement of drug-seeking as well as other addiction-related behaviors, making PCA a potentially valuable procedure for studying addiction vulnerability. Here, we describe materials and methods used to elicit PCA behavior from rats as well as analyze and interpret PCA behavior in individual experiments.     

Klassische Konditionierung agonistischen Verhaltens beim Syrischen Goldhamster (Mesocricetus auratus Waterhouse)

Nine different reactions of unconditioned agonistic behavior of golden hamsters (Mesocricetus auratus Waterhouse) which could be elicited by an air blow (UCS) were classically conditioned at a sound of a xylophone (tone g), a previously neutral stimulus. Tone g (CS) was paired with UCS for a different number of trials/day. In all animals exposed to over 20 pairings/day components of the agonistic behavior were brought under the control of Cs, but it was not possible to predict which one of the agonistic reactions would appear. Most of the animals generalized and also showed conditioned reactions (CR) when presenting tone c' instead of tone g. When utilizing a differential conditioning procedure the animals learned to discriminate between the different tones. Extinction of CR at tone g was reached after an individually different number of trials.     

Relation between the dynamics of the extinction process and the initial rate of hypothalamic self-stimulation in the rabbit

In experiments on rabbits with electrodes chronically implanted in the lateral hypothalamus, dynamics was studied of extinction of self-stimulation reaction as a result of cancellation of intracerebral reinforcement. General dynamics of extinction of the unreinforced instrumental actions and behavioural manifestations of orienting-investigating reaction were revealed. It was found, that in 30% of rabbits, the orienting reaction appearing as a result of "discordance" between expected and actual afferentation is attended by a species-specific form of behaviour, expressed in the form of hind paws synergic strokes against the floor. It is suggested that these strokes may be a somatic expression of a negative emotional state of animals during self-stimulation extinction. The comparison of extinction dynamics with the level of self-stimulation background frequency showed a relative independence of the strength of drive towards getting positive emotions on motivational effects created by electric stimulation of the reinforcing brain structures.     

Conditioned reflex reproduction of evoked potentials during reinforcement by electrostimulation of the hypothalamus]

Conditioned evoked potentials to stimulation of a limb, a light flash or a short tone were studied on rats in acute experiments with nembutal anaesthesia and in chronic experiments. Electrical stimulation of the hypothalamus was used as reinforcement. Following the pairings of conditioned and hypothalamic stimulation, the appearance of conditioned EP was recorded, as manifest in the period of the previously applied unconditioned signal after its omission. Their emergence was facilitated after high-frequency stimulation of the hypothalamus or administration of galantamine, an anticholinesteraze drug. Coagulation of the hypothalamus did not prevent any manifestation of conditioned evoked potentials.     

Pavlovian conditioning: pigeon nictitating membrane

A new Pavlovian conditioning preparation was developed using the nictitating membrane of the restrained pigeon. Either visual or auditory stimuli served as conditioned stimuli (CSs) with an unconditioned stimulus (US) of a puff of air to the cornea. Movement of the nictitating membrane constituted the conditioned and unconditioned responses (CR and UR). Conditioning was studied with the Kamin blocking procedure. In agreement with findings from other conditioning preparations, responding to the redundant stimulus was attenuated relative to a stimulus that received the same number of CS-US pairings in a compound-conditioning procedure. Although response attenuation occurred, substantial individual variation was observed within the blocking procedure, a finding with some precedent in the experimental literature. Theoretical analysis and neural-network simulations indicate that inter-subject variation in response attenuation may result from differences in the extent to which contextual stimuli contribute to the functional CS.     

豚鼠齿状回颗粒细胞在追踪性眨眼条件反应巩固过程中的活动

海马在追踪性眨眼条件反应的巩固过程中发挥重要作用,但解剖学上与其紧密联系的齿状回在此过程中的作用尚不清楚. 实验拟观察齿状回颗粒细胞在追踪性眨眼条件反应巩固过程中的放电活动,阐明齿状回在此海马依赖任务中所发挥的作用. 条件反射组动物 (n=8) 首先接受 200 ms 声音条件刺激,间隔 600 ms 后,再被给予 200 ms 吹气非条件刺激,多次重复配对,建立追踪性眨眼条件反应. 对照组动物 (n=8) 接受非配对出现的上述两种刺激. 采用在体单细胞外记录技术,研究习得条件反应豚鼠的齿状回颗粒细胞在条件反应巩固过程中的放电活动. 结果显示:a. 通过 14 天的训练,条件反射组动物均建立了追踪性眨眼条件反应,而非配对组动物则没有建立该条件反应;b. 齿状回颗粒细胞在追踪性眨眼条件反应的巩固过程中表现出不同的活动模式,如在声音条件刺激、间隔期或吹气非条件刺激出现后活动的增强. 这些结果提示:齿状回可能参与巩固追踪性眨眼条件反应所需的神经环路,其颗粒细胞在追踪性眨眼条件反应巩固过程中可能编码不同的信息.     

Extinction of a conditioned response in rainbow trout selected for high or low responsiveness to stress

Two lines of rainbow trout (Oncorhynchus mykiss) that exhibit divergent endocrine responsiveness to stressors also display disparate behavioral traits. To investigate whether the high-responding (HR) and low-responding (LR) fish also differ in cognitive function, the rate of extinction of a conditioned response was compared between the two lines. Groups of HR and LR fish were exposed to a paired conditioned stimulus (CS; water off) and unconditioned stimulus (US; confinement stressor). After exposure to 18 CS-US pairings, at least 70% of individuals of both lines acquired a conditioned response (CR) manifested as an elevation of blood cortisol levels on presentation of the CS only. Post-conditioning, the fish were tested by presentation of the CS at weekly intervals, for 4 weeks, with no further reinforcement, and the extinction of the CR in the two lines was compared. The decline in mean plasma cortisol levels after exposure to the CS over successive tests suggested that the CR was retained for a shorter period among the HR (<14 days) than LR fish (<21 days). The frequency of individuals within each line whose plasma cortisol levels indicated a stress response when exposed to the CS was significantly greater among the LR than HR fish at 14 and 21 days with no HR fish falling into this category at 21 days. At 28 days post-conditioning, there were no HR fish and only three LR fish were categorized as "stressed". These results suggest that there are differences in cognitive function between the two lines. Possible mechanisms underlying these differences are discussed.     

Neural-network simulations of two context-dependence phenomena

This paper describes simulations of two context-dependence phenomena in Pavlovian conditioning, using a neural-network model that draws on knowledge from neuroscience and makes no distinction between operant and respondent learning mechanisms. One phenomenon is context specificity or the context-shift effect, the decrease of conditioned responding (CR) when the conditioned stimulus (CS) is tested in a context different from the one in which it had been paired with the unconditioned stimulus (US). The other effect is renewal, the recovery of CR in the training context after extinction in another context. For specificity (simulation 1), two neural networks were first given 200 CS-US pairings in a context. Then, the CS was tested either in the training context or a new context. Output activations in the new context were substantially lower. For renewal (simulation 2), two networks were first given 200 CS-US pairings in a context, then 100 extinction trials in either the same context or a new one, and then tested back in the training context. Output activations during the test phase were substantially higher after extinction in a new context. The results are interpreted in terms of the dynamics of activations and weights.     

The vegetative component of a conditioned reflex]

Defensive and alimentary conditioned reflexes were studied on normal cats and cats with neural isolation of the neocortex. The cardiac component of the conditioned reflexes is elaborated in decorticated animals at a similar rate and is as steady as in normal cats. Motor conditioned reactions in decorticated cats are difficult to elaborate. Both in normal and decorticated cats unconditioned pain stimulation evokes tachycardia, while a conditioned signal, paired with this unconditioned stimulus, produces bradicardia. Ban assumption has been made that the primary conditioned reaction consists in the appearance of a certain emotional state which changes the cardiac rhythm in a typical way.     

Conditioned modification of viscerosensory evoked potentials during sleep and wakefulness in cats

The effects of classic conditioning on the viscerosensory evoked potentials (EPs) were studied in twenty cats during wakefulness (W), slow-wave-sleep (SWS) and paradoxical sleep (PS). Four types of the experiment were performed on four groups of animals. Weak, non-painful stimulation of the small intestine or of the left splanchnic nerve was used as conditional stimulus (CS) in all experiments. A painful or non-painful shock on the left radial nerve served as unconditional stimulus (US) which followed the CS with a delay of 500 ms. In the first and second series of experiments, the CS was paired with non-painful or painful CS during W. In the third and fourth types of experiment, weak US was used and conditioning was done during SWS or PS. The evoked responses were recorded from the primary (SI) and secondary (SII) somatosensory and associative (AS) cortex, the thalamus (VPL), hypothalamus (HPT) and dorsal hippocampus (HPC). In each experiment, the stimulus pairings resulted in a complex electrographic conditional response (CR) which included an amplitude increase of the late components of EP's (early CR) and the development of a wave of 500 ms latency (delayed CR). In the second experiment, however, a behavioural CR (limb flexion) also appeared. All these CRs proved to be extinguishable. The recall of CR established during W was successful in SWS. The traces of CS-US pairings during SWS could, however, be elicited only in SWS. Both establishment and recall of CR were unsuccessful during PS. The possible mechanism of the effects originating from an interaction of conditioning and sleep on the viscerosensory inputs of the brain are discussed.     

Effect of dalargin on the processes of memory and learning in the rat

In experiments on rats, the influence was studied of dalargin on the elaboration and preservation of various homogeneous and heterogeneous conditioned reflexes (CRs) elaborated in single and multiple pairings. The effect of dalargin on the processes of learning and memory was compared with the action of the peptide on the activity of hypothalamic neurones. Administration of dalargin delayed the elaboration of maze defensive CRs and practically did not affect the elaboration of two-way avoidance. The preservation of CR also deteriorated under the influence of dalargin. Administration of dalargin 10 min before the CRs testing did not prevent their reproduction. When using CRs elaborated in a single pairing, dalargin disturbed the preservation of the drinking CR and improved that of passive avoidance CR. Dalargin in this dose affected the emotional state of animals in the open field and did not significantly affect their motor activity. Dalargin suppressed impulse activity in 17 out of 22 tested neurones of the lateral hypothalamus, with maximum effect in 20-50 min after its administration. The obtained data show that the character of dalargin action on the elaboration of CR and mainly on its consolidation, depends on the character of the elaborated CR and is probably due to great extent to the effect of the peptide on the brain emotional mechanisms.     

Role of reuniens nucleus projections to the medial prefrontal cortex and to the hippocampal pyramidal CA1 area in associative learning

We studied the interactions between short- and long-term plastic changes taking place during the acquisition of a classical eyeblink conditioning and following high-frequency stimulation (HFS) of the reuniens nucleus in behaving mice. Synaptic changes in strength were studied at the reuniens-medial prefrontal cortex (mPFC) and the reuniens-CA1 synapses. Input/output curves and a paired-pulse study enabled determining the functional capabilities of the two synapses and the optimal intensities to be applied at the reuniens nucleus during classical eyeblink conditioning and for HFS applied to the reuniens nucleus. Animals were conditioned using a trace paradigm, with a tone as conditioned stimulus (CS) and an electric shock to the trigeminal nerve as unconditioned stimulus (US). A single pulse was presented to the reuniens nucleus to evoke field EPSPs (fEPSPs) in mPFC and CA1 areas during the CS-US interval. No significant changes in synaptic strength were observed at the reuniens-mPFC and reuniens-CA1 synapses during the acquisition of eyelid conditioned responses (CRs). Two successive HFS sessions carried out during the first two conditioning days decreased the percentage of CRs, without evoking any long-term potentiation (LTP) at the recording sites. HFS of the reuniens nucleus also prevented the proper acquisition of an object discrimination task. A subsequent study revealed that HFS of the reuniens nucleus evoked a significant decrease of paired-pulse facilitation. In conclusion, reuniens nucleus projections to prefrontal and hippocampal circuits seem to participate in the acquisition of associative learning through a mechanism that does not required the development of LTP.     

Reflection of the process of conditioned reflex formation in shifts of the steady potential level]

In chronic experiments on rabbits with non-polarizable electrodes shifts of steady potential level (SPL) are recorded from the brain surface during extinction of the orienting reaction and formation of a conditioned defensive reflex. During each of these processes they have their typical parameters and are respectively denoted by the author as: orienting (appearing in response to a new stimulus), conditioned (to a signal atimulus), unconditioned (to an electro-cutaneous stimulus) and trace SPL shifts (developing after stimuli pairing). Trace shifts are the earliest SPL shifts originating as a result of pairing. They are manifested more regularly, than conditioned ones, considerably exceed them in amplitude, may differ from them in their sign and reach maximum values in a few seconds after the pairing. It has been assumed that formation of conditioned temporal connections depends above all on the appearance of a new kind of activity, resulting from pairings and reflected in the SPL trace shifts. This activity possibly constitutes the neurodynamic and metabolic processes underlying memory consolidation.     

Training-Dependent Associative Learning Induced Neocortical Structural Plasticity: A Trace Eyeblink Conditioning Analysis

Studies utilizing general learning and memory tasks have suggested the importance of neocortical structural plasticity for memory consolidation. However, these learning tasks typically result in learning of multiple different tasks over several days of training, making it difficult to determine the synaptic time course mediating each learning event. The current study used trace-eyeblink conditioning to determine the time course for neocortical spine modification during learning. With eyeblink conditioning, subjects are presented with a neutral, conditioned stimulus (CS) paired with a salient, unconditioned stimulus (US) to elicit an unconditioned response (UR). With multiple CS-US pairings, subjects learn to associate the CS with the US and exhibit a conditioned response (CR) when presented with the CS. Trace conditioning is when there is a stimulus free interval between the CS and the US. Utilizing trace-eyeblink conditioning with whisker stimulation as the CS (whisker-trace-eyeblink: WTEB), previous findings have shown that primary somatosensory (barrel) cortex is required for both acquisition and retention of the trace-association. Additionally, prior findings demonstrated that WTEB acquisition results in an expansion of the cytochrome oxidase whisker representation and synaptic modification in layer IV of barrel cortex. To further explore these findings and determine the time course for neocortical learning-induced spine modification, the present study utilized WTEB conditioning to examine Golgi-Cox stained neurons in layer IV of barrel cortex. Findings from this study demonstrated a training-dependent spine proliferation in layer IV of barrel cortex during trace associative learning. Furthermore, findings from this study showing that filopodia-like spines exhibited a similar pattern to the overall spine density further suggests that reorganization of synaptic contacts set the foundation for learning-induced neocortical modifications through the different neocortical layers.     

Reproduction of the electrophysiologic correlates of a conditioned defense reflex following electroconvulsive activity]

Acute and chronic experiments on cats have shown the possibility of obtaining in one session conditioned EEG-responses and vegetative changes as well as conditioned motor reactions time-locked to the moment of the unconditioned pain stimulation omitted during testing. Electro-convulsive stimulation directly after elaboration prevents the appearance of conditioned motor reactions, while conditioned EEG and vegetative changes are retained after electric seizures. A conclusion has been drawn that the emotional component of conditioned reactions is not subjected to the amnestic effect of electro-convulsive action.     

Learned movements elicited by direct stimulation of cerebellar mossy fiber afferents

Definitive evidence is presented that the conditioned stimulus (CS) in classical conditioning reaches the cerebellum via the mossy fiber system. Decerebrate ferrets received paired forelimb and periocular stimulation until they responded with blinks to the forelimb stimulus. When direct mossy fiber stimulation was then given, the animals responded with conditioned blinks immediately, that is, without ever having been trained to the mossy fiber stimulation. Antidromic activation was prevented by blocking mossy fibers with lignocaine ventral to the stimulation site. It could be excluded that cerebellar output functioned as the CS. Analysis of latencies suggests that conditioned responses (CRs) are not generated by mossy fiber collaterals to the deep nuclei. Hence, the memory trace is probably located in the cerebellar cortex.     

The role of the lateral and medial hypothalamus in reproducing a motor reaction as the signal during the acquisition of classical conditioned reflexes]

In experiments on three dogs there was shown that testing electrostimulation of the lateral hypothalamus reproduced the motor reaction which is a signal stimulus at elaboration of classic alimentary conditioned reflexes (CRs) and did not reproduce it at elaboration of classic defensive CR. Testing electrostimulation of medial parts of the hypothalamus reproduced, as LH electrostimulation the "signal" motor reaction, but in less percentage of cases, during elaboration of classic alimentary CRs and did not reproduce it at elaboration of classic defensive CRs. The reproduction of the signal motor reaction at LH electrostimulation is connected with activation of backward conditioned connection from motivation structures of the hypothalamus to representation of the signal stimulus in the motor cortex.