Performance Of Conditioned Response Research Articles

A biomimetic afferent nervous system based on the flexible artificial synapse

Biomimetic afferent nervous system (ANS) is urgently needed in the booming development of neuromorphic chips and artificial intelligent robots. It is necessary to make biomimetic ANS stably respond to the real irritation (heat or touch), not the conventionally used electric stimuli, in a manner of low-power-consumption, flexibility and miniaturization. Here, we present a chip-like flexible ANS device by fusing the ion conductive elastomer (ICE) with the MXene artificial synapse. It can not only successfully generate stable response to the joint flexion behaviors and weak pulse at radial artery, but also the plastic neural response can be simulated. Theoretical explanation for the proposed biomimetic ANS device is investigated by integrating the simulated geometry deformation, ion migration theory and trap assisted tunnel effect. Furthermore, the proposed device is applied to mimic an interesting “operant conditioned reflex behavior” by using a typical “trial and error learning” experiment. The transformations from short-term memory to long-term memory during two operant conditioning reflex stages (training and experiencing) are implemented. Conclusively, the sensory behaviors in biological ANS are simulated by the proposed device, which demonstrates its powerful ability of generating plastic neuro-impulse to real stimuli, thereby granting it a new role to realize the anthropomorphic sensation.

Role of the motor cortex in the generation of classically conditioned eyelid and vibrissae responses

The eyelid motor system has been used for years as an experimental model for studying the neuronal mechanisms underlying motor and cognitive learning, mainly with classical conditioning procedures. Nonetheless, it is not known yet which brain structures, or neuronal mechanisms, are responsible for the acquisition, storage, and expression of these motor responses. Here, we studied the temporal correlation between unitary activities of identified eyelid and vibrissae motor cortex neurons and the electromyographic activity of the orbicularis oculi and vibrissae muscles and magnetically recorded eyelid positions during classical conditioning of eyelid and vibrissae responses, using both delay and trace conditioning paradigms in behaving mice. We also studied the involvement of motor cortex neurons in reflexively evoked eyelid responses and the kinematics and oscillatory properties of eyelid movements evoked by motor cortex microstimulation. Results show the involvement of the motor cortex in the performance of conditioned responses elicited during the classical conditioning task. However, a timing correlation analysis showed that both electromyographic activities preceded the firing of motor cortex neurons, which must therefore be related more with the reinforcement and/or proper performance of the conditioned responses than with their acquisition and storage.

Impairments to Visuomotor Functions on Development of MPTP-Induced Parkinsonism-Like Syndrome in Monkeys

This study summarizes results from studies of behavior and visuomotor functions in monkeys (rhesus macaques) during development of parkinsonism-like syndrome induced by chronic administration of small doses of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). An operant conditioned reflex method was used to study the amplitude-time parameters of visually evoked saccades. Development of MPTP-induced syndrome was associated with increases in the latent periods of saccades, decreases in their peak velocities, and degradation of their accuracy. These oculomotor effects were apparent at the presymptomatic stage of MPTP syndrome, such that they can be regarded as early markers of parkinsonism-like syndrome in monkeys. The development of MPTP syndrome produced cognitive and motor deficits on execution of a spatially hindered operant task consisting of a food-procuring manipulation in peripersonal space.

The Functions of Dopamine in Operant Conditioned Reflexes

Dopamine neurons are activated by stimuli of both positive and negative modality according to the magnitude of the “willing effort” required to produce encouragement or avoidance of punishment. Acquisition of an operant conditioned reflex starts when the target of the movement (an external target, e.g., a lever, a location within a maze, or an internal target, e.g., a posture), based on the Pavlovian association mechanism (possibly dopamine-independent), becomes attractive or repulsive and acquires “incentive salience attribution”, the motive force of which is the “dopamine drive.” From the very beginning of execution of the operant conditioned reflex, dopamine is secreted in the window between activation of the conditioned signal and the movement, where it combines “activation of the central motor system of behavior” [Konorski, 1970] and modulation of synaptic plasticity for further learning. The operant movement performed by the animal under the influence of the dopamine drive is reinforced by diminution of the drive.

Timing correlations between cerebellar interpositus neuronal firing and classically conditioned eyelid responses in wild-type and Lurcher mice

Classical eyeblink conditioning is an experimental model widely used for the study of the neuronal mechanisms underlying the acquisition of new motor and cognitive skills. There are two principal interpretations of the role of the cerebellum in the learning of eyelid conditioned responses (CRs). One considers that the cerebellum is the place where this learning is acquired and stored, while the second suggests that the cerebellum is mostly involved in the proper performance of acquired CRs, implying that there must be other brain areas involved in the learning process. We checked the timing of cerebellar interpositus nucleus (IPN) neurons’ firing rate with eyelid CRs in both wild-type (WT) and Lurcher (a model of cerebellar cortex degeneration) mice. We used delay and trace conditioning paradigms. WT mice presented a better execution for delay vs. trace conditioning and also for these two paradigms than did Lurcher mice. IPN neurons were activated during CRs following the activation of the orbicularis oculi muscle. Firing patterns of IPN neurons were altered in Lurcher mice. In conclusion, the cerebellum seems to be mostly related with the performance of conditioned responses, rather than with their acquisition.

Вплив інтраназального введення дофаміну на когнітивні процеси та загальнорухову активність щурів при стресі

In spontanepously hypertensive rats (SHR) we studied the influence of intranasal administration of dopamine (DA) on realization of food operant conditioned reflex (OCR) and motor activity (locomotion, bars, stopping beating, grooming) in a interstimulation period in a norm and in the conditions of stressed influences. The state of sharp stress was caused by application of intensive acoustic irritation is a loud sound operating during realization ofOCR. Stress caused a brake of conditioned reflex activity, immobilization ofanimals, weakening of attention to the conditional stimulus. On a background intranasal application DA (0.15 mgs/of kg) the effect of stress on voice irritation was eliminated, not rendering brake influence on OCR and motor activity. DA via oppressing the reactions of alarm and fear strengthened the focused attention that assisted the improvement of integrative function in the concrete situation of realization of OCR.

Effect of stimulation of β adrenoreceptors on conditioned reflex-related spike activity of neurons of the cat somatosensory cortex

Using extracellular recording of impulse activity of pyramidal neurons of the cat somatosensory cortex generated in the course of realization of an operant conditioned reflex, we examined effects of microiontophoretic applications of an agonist of β2 adrenoreceptors, metaproterenol, and of an antagonist of β adrenoreceptors, propranolol, on the frequency of this impulsation. Applications of propranolol induced intensification of both background and reflex-related spiking. The effect of metaproterenol was manifested as moderate intensification of background discharges, a noticeable increase in the frequency of evoked impulsation, and an increase in the latency of impulse reactions. It is supposed that noradrenergic projections to the neocortex intensify neuronal activity via activation of β2 adrenoreceptors and suppress this activity via influencing mostly β1 adrenoreceptors. Such effects of synaptically active agents should probably be taken into account in the treatment of neurological diseases, namely epilepsy, neurodegenerative disorders, psychoemotional shifts, etc., which are accompanied by emotional and cognitive disorders.

Contextual modulation of conditioned responses: Role of the ventral subiculum and nucleus accumbens.

The performance of conditioned responses (CRs) is diminished when trained subjects are tested in a novel context. This study tested the hypothesis that the flow of contextual information along the disynaptic "ESA" (entorhinal cortex-ventral subiculum-nucleus accumbens) pathway is responsible for context-related modulation of CRs. Rabbits received electrolytic or sham lesions of the ventral subiculum followed by discriminative avoidance conditioning and counterbalanced extinction sessions in the original training context, a novel context, and the original training context with a novel cue. Neuronal activity was recorded simultaneously in the nucleus accumbens, cingulate cortex, and basolateral amygdala. The lesions did not affect the acquisition of avoidance behavior or prevent the reduction of CRs in response to a novel cue. However, the lesions did reduce CR incidence during extinction, and they did eliminate a further novel-context-induced CR reduction found in controls. In addition, lesions disrupted context-dependent neuronal responses in the nucleus accumbens but not in the cingulate cortex or amygdala. These findings are interpreted as supportive of the hypothesis that the ESA pathway mediates contextual modulation of CRs during extinction.

Effects of BT-melanin on recovery of operant conditioned reflexes in rats after ablation of the sensorimotor cortex

An increase in corticofugal plasticity was demonstrated in adult rats after unilateral ablation of the sensorimotor cortex accompanied by intramuscular administration of low concentrations of BT-melanin solution. The result was acceleration of the process of compensatory recovery in the central nervous system, this being supported by the rapid recovery of a previously acquired operant conditioned reflex and movement of the paralyzed limb as compared with control animals. It is suggested that compensation of the motor deficit arising after ablation of the sensorimotor cortex is mediated by the ability of the two major motor systems of the brain - the corticospinal and the corticorubrospinal - to exhibit mutual substitution of their functions. This phenomenon of the functional switching of descending influences also occurred in rats of the control group not exposed to BT-melanin. However, the difference between the recovery times of the operant conditioned reflex and limb movement in the control and experimental groups provided evidence of an apparent acceleration in these processes as a result of BT-melanin. These results suggest that low concentrations of BT-melanin may have applied uses.

Organization of Frontohippocampal Neuronal Networks in Cats in Different Types of Directed Behavior

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

The Effects of Systemic Administration of Selective Antagonists of Dopamine D1 and D2/D3 Receptors on Food-Related and Defensive (escape responses) Conditioned Paw-Placing Responses in Cats

Experiments were performed on cats to study the effects of systemic administration of antagonists of dopaminergic transmission on food-related and defensive (an escape response) operant conditioned reflexes acquired on the basis of the innate response of placing the forepaw on a support. Selective blockade of D1 receptors with SCH23390 (0.005-0.1 mg/kg) completely and selective blockade of D2/D3 receptors with raclopride (0.1-0.25 mg/kg) partially suppressed both reflexes. At these doses, both blockers had stronger actions on the defensive conditioned escape reflex than the food-related reflex: SCH23390 had significantly stronger inhibitory effects on both reflexes than raclopride.

Activity of Neurons in the Basal Magnocellular Nucleus During Performance of an Operant Task

Spike activity was studied in 95 neurons in the basal magnocellular nucleus in rabbits during spontaneous behavior and during performance of a conditioned operant response. Nearly half the neurons (48.4%) showed significant (p < 0.05) negative correlations between spontaneous discharges and the power of the frontal lobe EEG delta rhythm; most of these cells could be identified as cholinergic projection neurons. Neurons of this group had predominantly excitatory responses to the conditioned stimulus during performance of the operant task, while the responses to the conditioned stimulus of presumptively non-cholinergic neurons, not projecting to the cortex, were mainly inhibitory. The activatory responses of neurons in the basal magnocellular nucleus to the conditioned stimulus were markedly stronger while the animals performed the operant response as compared with performances in which there was no response to the conditioned stimulus. These results provide evidence that the basal magnocellular nucleus supports the level of waking and attending required for performance of operant conditioned reflex activity.

Acetylcholine release in the hippocampus during the operant conditioned reflex and the footshock stimulus in rats

The activity of the septo-hippocampal cholinergic pathway was investigated by measuring changes in the extracellular acetylcholine (ACh) levels in the hippocampus, by means of microdialysis, during the operant conditioned reflex and the repeated footshock stimulus. Microdialysis samplings were conducted in a Skinner box where lights were delivered as conditioned stimuli (CS) paired with footshocks as unconditioned stimuli (US). Two groups of rats were used. Extracellular ACh and choline (Ch) in samples collected at 6 min intervals were assessed by high-performance liquid chromatography with electrochemical detection. The elevation of hippocampus ACh was observed in the two experimental groups. The increase in ACh during aversive stimulus (footshock) was significantly larger and was probably related to the number of footshocks. There might be moderate increase in the hippocampal ACh release during the retrieval of information. The concentration of choline showed no significant fluctuation in the two groups during the whole process. This experiment explored in more detail hippocampal cholinergic activity in relation to the two different procedures.

Functional Asymmetry of the Frontal Cortex and Lateral Hypothalamus of Cats During an Operant Food-Related Conditioned Reflex

The extent of correlation and the latency of evoked potentials to sound, recorded bilaterally in the frontal cortex and lateral hypothalamus of cats, were studied at different stages of the acquisition of an operant food-related reflex and during sudden transfer to 30% food reinforcement. High correlation coefficients between the evoked responses of the cortex and hypothalamus with left-sided dominance were seen in conditions of high levels of food motivation at the beginning of each experiment and in conditions of the high-probability appearance of the acquired conditioned reflex throughout the rest of the experiment. Comparison of the peak latencies of the early positive (P55-80) components of evoked potentials on the right and left sides showed that shorter latent periods were seen in the cortex on the left side at all behavioral stages, while this occurred (on the left side) in the hypothalamus only when the conditioned reflex was unfixed, while after fixation of the reflex and provision of 30% reinforcement, shorter latent periods were seen on the right side. It is concluded that the high level of left-sided correlation of evoked potentials in the hypothalamus was associated with the motivational and motor components of purposive behavior and was not associated with the emotional tension of the animals provoked by the disruption of the food reinforcement stereotype.

Interneuronal Frontohippocampal Interactions in Cats Trained to Choose on the Basis of Reinforcement Quality

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

Characteristics of the actions of neurotensin on motor reactions in rats in response to positive and negative conditioned signals.

This study addressed the effects of microinjections of neurotensin into the caudate nucleus and substantia nigra on the performance of motor reactions in response to positive and negative conditioned signals, as well as the post-effects of microinjections in subsequent experiments. Neurotensin had positive effects on the extinction of non-reinforced motor reactions. Neurotensin had no effect on the number of motor responses to the non-reinforced signal, though the number decreased in subsequent experiments. There was an increase in the latent period of responses as compared with controls. The effect of neurotensin at the level of the caudate nucleus was more marked than that at the level of the substantia nigra. Neurotensin microinjections had no marked effect on performance of conditioned responses to positive signals. The behavioral effects of neurotensin are associated with normalization of the interactions of the brain's monoaminergic systems. It is suggested that the positive actions of neurotensin on extinction of motor responses to negative signals result from the formation of a contextual conditioned emotional state in the animals, this facilitating optimization of conditioned reflex activity.

Analysis of glucose and lactate in hippocampal dialysates of rats during the operant conditioned reflex using microdialysis

Changes of extracellular glucose and lactate in hippocampus for freely moving rats during the operant conditioned reflex were examined simultaneously. Samples of the dialysate were assayed for both glucose and lactate using in vivo microdialysis and a microbore flow injection analysis–immobilized enzyme reactor-electrochemical detection (FIA–IMER-ECD) system. Microdialysis samplings were conducted in a Skinner box where lights were delivered as conditioned stimuli (CS) paired with foot shocks as unconditioned stimuli (US). In the treatment group the concentration of glucose and lactate showed no fluctuations during the whole process. However, in the control group in which the rats were exposed to many foot shocks, lactate levels decreased by 19% below baseline during the behavioral session and glucose showed a delayed decrease (by 18%). Compared with glucose, lactate can immediately indicate the dynamic changes in brain.

NMDA-dependent and NMDA-independent neural processes in the bicucculline-disinhibited motor cortex of the cat during the acquisition and reproduction of a conditioned paw-on-support placing reflex.

Neuron activity was recorded in the motor area of the cat cortex during acquisition of an operant conditioned reflex consisting of placing the forepaw on a support in conditions of local disinhibition by spontaneous diffusion of the GABA(A) receptor blocker bicucculline from the recording micropipette. The conditioned signal was electrical stimulation of the parietal cortex with a train of 3-5 impulses. Addition of 2-amino-5-phosphopentanoic acid (APV), an NMDA glutamate receptor blocker, led to disappearance of the secondary excitatory components (in the poststimulus interval 30-120 msec) from neuronal responses in the disinhibited cortex both to the "indifferent" (before training) and the conditioned stimulation of the parietal cortex, while excitatory reactions associated with elevation and placing of the paw on the support showed no significant change in the presence of APV. Acquisition of the operant conditioned reflex was accompanied by an increase in the amplitude (p < 0.006) and duration (p < 0.00002) of secondary responses and decreases in their latent periods (p < 0.00002). In some cases--in fixed conditioned reflexes--secondary responses to conditioned stimulation in the disinhibited cortex were transformed into trains of epileptiform discharges. The hypothesis that changes in neuronal reactions in the disinhibited cortex during learning are based on increases in the efficiency of horizontal (collateral) connections between pyramidal neurons in layers II and III of the cortex is discussed.

Activity of neurons in the pedunculopontine nucleus during a food-related operant conditioned reflex.

The activity of 91 neurons in the compact and diffuse zones of the pedunculopontine nucleus of freely mobile rabbits was studied during performance of a food-related operant conditioned reflex. A total of 37.4% of the neurons recorded showed reactivity to the conditioned stimulus, which is evidence that the pedunculopontine nucleus is involved in operant learning. A significant predominance of excitatory responses to the conditioned stimulus and to food reinforcement was demonstrated. The main patterns of cell responses were identified, these reflecting the nature of the effect of the conditioned stimulus on neuron activity, the structure of the behavioral act, and the properties of the reinforcement, and demonstrating a relationship between the pedunculopontine nucleus and the processes of attention, motor learning, and reinforcement. Differences were seen in the associative reactive properties of the compact and diffuse zones of the pedunculopontine nucleus to the conditioned stimulus and reinforcement, which is evidence for the functional diversity of this formation and suggests a leading role for the cholinergic compact zone in food-related operant learning and reinforcement, the diffuse zone having a leading role in food-related classical conditioned-reflex learning.

Plasticity of social behavior in Drosophila.

This article presents results obtained from studies of the plasticity of changes in social behavior in Drosophila (interactions between individuals in groups) in conditions of homo- and heterogeneous environments. This is the first report of data illustrating self-starting acquisition by female Drosophila of a classical conditioned reflex to contextual factors signaling possible threats from other individuals and blocking the initiation of activity. A previously described operant conditioned reflex also helped flies avoid aggression from other individuals and make more efficient use of food resources by decreasing the initially high level of activity. Classical conditioning had the effect that the fly did not need to repeat acquisition of the conditioned reflex each time: when placed into an analogous situation, the fly's activity automatically decreased as a result of exposure to the conditioned stimulus, i.e., contextual factors.