Operant Conditioning Task Research Articles

Progressive-ratio Responding for Palatable High-fat and High-sugar Food in Mice

Foods that are rich in fat and sugar significantly contribute to over-eating and escalating rates of obesity. The consumption of palatable foods can produce a rewarding effect that strengthens action-outcome associations and reinforces future behavior directed at obtaining these foods. Increasing evidence that the rewarding effects of energy-dense foods play a profound role in overeating and the development of obesity has heightened interest in studying the genes, molecules and neural circuitry that modulate food reward. The rewarding impact of different stimuli can be studied by measuring the willingness to work to obtain them, such as in operant conditioning tasks. Operant models of food reward measure acquired and voluntary behavioral responses that are directed at obtaining food. A commonly used measure of reward strength is an operant procedure known as the progressive ratio (PR) schedule of reinforcement. In the PR task, the subject is required to make an increasing number of operant responses for each successive reward. The pioneering study of Hodos (1961) demonstrated that the number of responses made to obtain the last reward, termed the breakpoint, serves as an index of reward strength. While operant procedures that measure changes in response rate alone cannot separate changes in reward strength from alterations in performance capacity, the breakpoint derived from the PR schedule is a well-validated measure of the rewarding effects of food. The PR task has been used extensively to assess the rewarding impact of drugs of abuse and food in rats (e.g., 6-8), but to a lesser extent in mice. The increased use of genetically engineered mice and diet-induced obese mouse models has heightened demands for behavioral measures of food reward in mice. In the present article we detail the materials and procedures used to train mice to respond (lever-press) for a high-fat and high-sugar food pellets on a PR schedule of reinforcement. We show that breakpoint response thresholds increase following acute food deprivation and decrease with peripheral administration of the anorectic hormone leptin and thereby validate the use of this food-operant paradigm in mice.

Observational learning in mice can be prevented by medial prefrontal cortex stimulation and enhanced by nucleus accumbens stimulation

The neural structures involved in ongoing appetitive and/or observational learning behaviors remain largely unknown. Operant conditioning and observational learning were evoked and recorded in a modified Skinner box provided with an on-line video recording system. Mice improved their acquisition of a simple operant conditioning task by observational learning. Electrical stimulation of the observer's medial prefrontal cortex (mPFC) at a key moment of the demonstration (when the demonstrator presses a lever in order to obtain a reward) cancels out the benefits of observation. In contrast, electrical stimulation of the observer's nucleus accumbens (NAc) enhances observational learning. Ongoing cognitive processes in the demonstrator could also be driven by electrical stimulation of these two structures, preventing the proper execution of the ongoing instrumental task (mPFC) or stopping pellet intake (NAc). Long-term potentiation (LTP) evoked in these two cortical structures did not prevent the acquisition or retrieval process--namely, mPFC and/or NAc stimulation only prevented, or modified, the ongoing behavioral process. The dorsal hippocampus was not involved in either of these two behavioral processes. Thus, both ongoing observational learning and performance of an instrumental task require the active contribution of the mPFC and/or the NAc.

Plasticity of Adult Sensorimotor System

Plasticity of Adult Sensorimotor System

Social facilitation of d-amphetamine self-administration in rats.

The link between social influence and drug abuse has long been established in humans. However, preclinical animal models of drug abuse have only recently begun to consider the role of social influence. Since social factors influence the initiation and maintenance of drug use in humans, it is important to include these factors in preclinical animal models. The current study examined the effects of the presence of a social partner on responding for sucrose pellets under various motivational conditions, as well as on d-amphetamine (AMPH) self-administration. Rats were trained to lever press for either sucrose or AMPH (0.01 or 0.1 mg/kg/infusion unit dose). Following response stability, a novel same-sex conspecific was presented in an adjacent compartment separated by a clear divider, and responding for sucrose or AMPH reward was measured. Rats were allowed to restabilize, and subsequently given an additional partner presentation. Presence of the social partner increased responding only during the first pairing with the AMPH 0.1 mg/kg/infusion unit dose, whereas inhibition of responding was observed during the first pairing during access to the 0.01 mg/kg/infusion unit dose. Under free feed conditions, inhibition of sucrose pellet responding was observed in the presence of the social partner, but this effect was attenuated under food restriction. In contrast, the results demonstrate social facilitation of AMPH self-administration at a high unit dose, thus extending the influence of social factors to an operant conditioning task. This model of social facilitation may have important implications as a preclinical model of social influence on drug abuse.

AM2389, a high-affinity, in vivo potent CB1-receptor-selective cannabinergic ligand as evidenced by drug discrimination in rats and hypothermia testing in mice

The endocannabinoid signaling system (ECS) has been targeted for developing novel therapeutics since ECS dysfunction has been implicated in various pathologies. Current focus is on chemical modifications of the hexahydrocannabinol (HHC) nabilone (Cesamet(®)). To characterize the novel, high-affinity cannabinoid receptor 1 (CB(1)R) HHC-ligand AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol in two rodent pre-clinical assays. CB(1)R mediation of AM2389-induced hypothermia in mice was evaluated with AM251, a CB(1)R-selective antagonist/inverse agonist. Additionally, two groups of rats discriminated the full cannabinergic aminoalkylindole AM5983 (0.18 and 0.56mg/kg) from vehicle 20min post-injection in a two-choice operant conditioning task motivated by 0.1% saccharin/water. Generalization/substitution tests were conducted with AM2389, AM5983, and Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Δ(9)-THC (30mg/kg)-induced hypothermia exhibited a faster onset and shorter duration of action compared with AM2389 (0.1 and 0.3mg/kg). AM251 (3 and 10mg/kg) attenuated/blocked hypothermia induced by 0.3mg/kgAM2389. In drug discrimination, the order of potency was AM2389 > AM5983 > Δ(9)-THC with ED(50) values of 0.0025, 0.0571, and 0.2635mg/kg, respectively, in the low-dose condition. The corresponding ED(50) values in the high-dose condition were 0.0069, 0.1246, and 0.8438mg/kg, respectively. Onset of the effects of AM2389 was slow with a protracted time-course; the functional, perceptual in vivo half-life was approximately 17h. This potent cannabinergic HHC exhibited a slow onset of action with a protracted time-course. The AM2389 chemotype appears well suited for further drug development, and AM2389 currently is used to probe behavioral consequences of sustained ECS activation.

Evaluating fatigue in lupus-prone mice: Preliminary assessments

Fatigue is a debilitating condition suffered by many as the result of chronic disease, yet relatively little is known about its biological basis or how to effectively manage its effects. This study sought to evaluate chronic fatigue by using lupus-prone mice and testing them at three different time periods. Lupus-prone mice were chosen because fatigue affects over half of patients with Systemic Lupus Erythematosus. Eleven MLR+/+ (genetic controls) and twelve MLR/MpJ-Fas<lpr>/J (MRL/lpr; lupus-prone) mice were tested three times: once at 12, 16 and 20weeks of age. All mice were subjected to a variety of behavioral tests including: forced swim, post-swim grooming, running wheel, and sucrose consumption; five of the MLR+/+ and five of the MLR/lpr mice were also tested on a fixed ratio-25 operant conditioning task. MRL/lpr mice showed more peripheral symptoms of lupus than controls, particularly lymphadenopathy and proteinuria. Lupus mice spent more time floating during the forced swim test and traveled less distance in the running wheel at each testing period. There were no differences between groups in post-swim grooming or in number of reinforcers earned in the operant conditioning task indicating the behavioral changes were not likely due simply to muscle weakness or motivation. Correlations between performance in the running wheel, forced swim test and sucrose consumption were conducted and distance traveled in the running wheel was consistently negatively correlated with time spent floating. Based on these data, we conclude that the lupus-prone mice were experiencing chronic fatigue and that running wheel activity and floating during a forced swim test can be used to evaluate fatigue, although these data cannot rule out the possibility that both fatigue and a depressive-like state were mediating these effects.

Redirected behavior in learning tasks: The commercial laying hen (Gallus gallus domesticus) as model

Redirected behaviors occur when some course of action is thwarted or inhibited (frustration). They also occur as adjunctive behaviors in operant conditioning tasks, where they might reflect frustration about unrewarded responses. Because frustration is associated with stress, which could interfere with learning and memory, we studied whether the occurrence of redirected behavior is correlated with learning success in a series of visual-cue discrimination tasks. Eleven hens, aged 34 wk, were tested on acquisition, reversal, extinction, and relearning of a simple visual discrimination task. The experimenters randomly assigned red and blue cardboard discs as discriminative stimuli. A correct response was recorded when a hen pecked at the correct disc. The learning criterion was 90% correct responses in 20 trials in 2 consecutive task sessions. The following data were documented: number of pecks needed to achieve the learning criterion, latency in choosing, pecks at the experimenter, and pecks at the surroundings. The behavioral responses were analyzed using linear mixed model ANOVA. Redirected pecking at the surroundings was a significant indicator of learning failure in that the more the hens performed this behavior, the more trials they needed to complete the discrimination tasks (P = 0.012). The number of pecks at the experimenter during the tasks significantly influenced learning success (P = 0.020), with hens directing more pecks at the experimenter during reversal, reaching the learning criterion in fewer trials (P = 0.027). The more the hens pecked at the experimenter during acquisition and extinction, however, the more trials they needed to meet the learning criteria (acquisition: P = 0.048; extinction: P = 0.003). Thus, laying hens are susceptible to the effects of frustration as measured in terms of redirected pecking elicited by operant procedures in visual discrimination tasks. In general, any situation in which a desirable goal is obstructed or an expected reward is omitted may lead to frustration-related activities, such as redirected behavior, which could in turn lead to abnormal behavior and welfare issues for the animals.

Naloxone attenuation of ethanol-reinforced operant responding in infant rats in a re-exposure paradigm

Early ethanol exposure promotes ethanol reinforcement, mediated perhaps by ethanol's motivational effects. The opioid system mediates ethanol reinforcement, at least in part. Modulation of consummatory and seeking behaviors by the opioid system was tested in terms of ethanol or sucrose operant self-administration. Wistar-derived infant rats were tested in an operant conditioning task. (1) Infants were trained on postnatal days (PDs) 14-17 to obtain 5% sucrose and 3.75% ethanol or water, and evaluated in an extinction session at PD 18. (2) Ethanol (3.75%) was used as reinforcer. At PDs 16-17, 6 h before operant task, pups were re-exposed to ethanol after naloxone injection (0 or 1 mg/kg). (3) Sucrose (5%) acted as reinforcer. Pups were re-exposed to sucrose after naloxone injection. (4) A PD 18 re-exposure trial in which pups were injected with naloxone and re-exposed to ethanol was added. Sucrose and ethanol promoted higher levels of operant responding than water during training and extinction. Re-exposure to ethanol preceded by naloxone decreased nose-poking. A similar profile was observed towards sucrose. No seeking behavior was observed in pups re-exposed to ethanol following naloxone injection during PDs 16-18. Self-administration of ethanol was established in terms of operant responding in preweanling rats with no previous exposure to the drug. Pairing of naloxone with ethanol, at a point separate in time from operant responding, reduced ethanol reinforcement. This indicated participation of the opioid system in ethanol reinforcement. This effect seems not to be unique to ethanol but also is observable when sucrose acts as reinforcer.

Posterior hypothalamic nucleus deep brain stimulation restores locomotion in rats with haloperidol-induced akinesia but not skilled forelimb use in pellet reaching and lever pressing

Recent studies have shown that electrical stimulation of the posterior hypothalamic nucleus (PH) facilitates locomotion in control rats, and rats were made akinetic by dopaminergic blockade via haloperidol or dopamine depletion by the neurotoxin 6-hydroxydopamine. These findings suggest that PH stimulation might be a promising treatment for akinesia associated with dopamine loss in Parkinson's disease. The present study further examined the positive effects of PH stimulation on behavior by characterizing its potential facilitatory effects on tasks that require skilled movements. Rats were trained to reach for food pellets with a forelimb (skilled reaching) or press a bar in an operant conditioning task for food. PH stimulation in undrugged rats not only facilitated locomotion in each of the tasks, but also impaired performance of the skilled movement components of the tasks. Haloperidol reduced locomotion and skilled movement, and PH stimulation only restored locomotion. The results are discussed in relation to the idea that PH stimulation selectively facilitates locomotor behavior and may have limited use in restoring impairments in skilled movements and consummatory behavior that results from dopaminergic depletion.

Automated auditory recognition training and testing

Laboratory training and testing of auditory recognition skills in animals is important for understanding animal communication systems that depend on auditory cues. Songbirds are commonly studied because of their exceptional ability to learn complex vocalizations. In recent years, mounting interest in the perceptual abilities of songbirds has increased the demand for laboratory behavioural training and testing paradigms. Here, we describe and demonstrate the success of a method for auditory discrimination experiments, including all the necessary hardware, training procedures and freely-available, versatile software. The system can run several behavioural training and testing paradigms, including operant (go-nogo, stimulus preference, and two-alternative forced choice) and classical conditioning tasks. The software and some hardware components can be used with any laboratory animal that learns and responds to sensory cues. The peripheral hardware and training procedures are designed for use with songbirds and auditory stimuli. Using the go-nogo paradigm of the training system, we show that adult zebra finches learn to recognize and correctly classify individual female calls and male songs. We also show that learning the task generalizes to new stimulus classes; birds that learned the task with calls subsequently learned to recognize songs faster than did birds that learned the task and songs at the same time.

Learning an operant conditioning task differentially induces gliogenesis in the medial prefrontal cortex and neurogenesis in the hippocampus.

Circuit modification associated with learning and memory involves multiple events, including the addition and remotion of newborn cells trough adulthood. Adult neurogenesis and gliogenesis were mainly described in models of voluntary exercise, enriched environments, spatial learning and memory task; nevertheless, it is unknown whether it is a common mechanism among different learning paradigms, like reward dependent tasks. Therefore, we evaluated cell proliferation, neurogenesis, astrogliogenesis, survival and neuronal maturation in the medial prefrontal cortex (mPFC) and the hippocampus (HIPP) during learning an operant conditioning task. This was performed by using endogenous markers of cell proliferation, and a bromodeoxiuridine (BrdU) injection schedule in two different phases of learning. Learning an operant conditioning is divided in two phases: a first phase when animals were considered incompletely trained (IT, animals that were learning the task) when they performed between 50% and 65% of the responses, and a second phase when animals were considered trained (Tr, animals that completely learned the task) when they reached 100% of the responses with a latency time lower than 5 seconds. We found that learning an operant conditioning task promoted cell proliferation in both phases of learning in the mPFC and HIPP. Additionally, the results presented showed that astrogliogenesis was induced in the medial prefrontal cortex (mPFC) in both phases, however, the first phase promoted survival of these new born astrocytes. On the other hand, an increased number of new born immature neurons was observed in the HIPP only in the first phase of learning, whereas, decreased values were observed in the second phase. Finally, we found that neuronal maturation was induced only during the first phase. This study shows for the first time that learning a reward-dependent task, like the operant conditioning, promotes neurogenesis, astrogliogenesis, survival and neuronal maturation depending on the learning phase in the mPFC-HIPP circuit.

Impaired striatum-dependent behavior in GASP-1-knock-out mice

G protein-coupled receptor (GPCR) associated sorting protein-1 (GASP-1) is suspected to play a key role in recycling and degradation of several GPCRs. In a previous study, we have shown that GASP-1-knock-out (GASP-1-KO) mice displayed deficits in acquiring a cocaine self-administration task, associated with an exacerbated down-regulation of striatal dopaminergic and cholinergic receptors. Among several possibilities, GASP-1 deficiency could have impaired memory processes underlying the acquisition of the operant conditioning task. Therefore, the present study investigated cognitive performances of GASP-1-KO mice and their wild-type littermates (WT) in a broad variety of memory tasks. Consistent with a deficit in procedural memory, GASP-1-KO mice showed delayed acquisition of a food-reinforced bar-press task. During water-maze training in hidden- or visible-platform paradigms, mutant and WT mice acquired the tasks at the same rate. However, GASP-1 mice exhibited persistent thigmotaxic swimming, longer distance to the platform, and reduced swim speed. There was no deficit in several tasks requiring simple behavioral responses (Barnes maze, object recognition and passive avoidance tasks). Thus, the ability to acquire and/or express complex responses seems affected in GASP-1-deficient mice. Hippocampal functions were preserved, as the retention of an acquired memory in spatial tasks remained unaffected. The pattern of behavioral deficits observed in GASP-1-KO mice is coherent with current knowledge on the role of striatal GPCRs in acquisition/expression of skilled behavior and in motivation. Together with the previous findings, the so far established phenotype of GASP-1-KO mice makes them a potentially exciting tool to study striatal functions.

Focus on the positive: Computational simulations implicate asymmetrical reward prediction error signals in childhood attention-deficit/hyperactivity disorder

A number of hypotheses have suggested that the principal neurological dysfunction responsible for the behavioural symptoms associated with Attention-Deficit/Hyperactive Disorder (ADHD) is likely rooted in abnormal phasic signals coded by the firing rate of midbrain dopamine neurons. We present a formal investigation of the impact atypical phasic dopamine signals have on behaviour by applying a T D ( λ ) reinforcement learning model to simulations of operant conditioning tasks that have been argued to quantify the hyperactive, inattentive and impulsive behaviour associated with ADHD. The results presented here suggest that asymmetrically effective dopamine signals encoded by a punctate increase or decrease in dopamine levels provide the best account for the behaviour of children with ADHD as well as an animal model of ADHD, the spontaneously hypertensive rat (SHR). The biological sources of this asymmetry are considered, as are other computational models of ADHD.

Effect of modafinil on learning performance and neocortical long-term potentiation in rats

Modafinil is a novel wake-promoting agent whose effects on cognitive performance have begun to be addressed at both preclinical and clinical level. The present study was designed to investigate in rats the effects of chronic modafinil administration on cognitive performance by evaluating: (i) working and reference memories in an Olton 4 × 4 maze, and (ii) learning of a complex operant conditioning task in a Skinner box. In addition, the effect of modafinil on the ability of the rat frontal cortex to develop long-term potentiation (LTP) was also studied . Chronic modafinil did not significantly modify working memory errors but decreased long-term memory errors on the Olton 4 × 4 maze, meaning that the drug may have a favourable profile on performance of visuo-spatial tasks (typically, a hippocampus-dependent task) when chronically administered. On the other hand, chronic modafinil resulted in a marked decrease of successful responses in a complex operant conditioning learning, which means that repeated administration of the drug influences negatively problem-solving abilities when confronting the rat to a sequencing task (typically, a prefrontal cortex-dependent task). In addition, in vivo electrophysiology showed that modafinil resulted in impaired capacity of the rat prefrontal cortex to develop LTP following tetanization. It is concluded that modafinil can improve the performance of spatial tasks that depend almost exclusively on hippocampal functioning, but not the performance in tasks including a temporal factor where the prefrontal cortex plays an important role. The fact that modafinil together with preventing operant conditioning learning was also able to block LTP induction in the prefrontal cortex, suggests that the drug could interfere some critical component required for LTP can be developed, thereby altering neuroplastic capabilities of the prefrontal cortex.

Determination of Odor Detection Threshold in the Gottingen Minipig

The aim of the study was to examine the ability of Göttingen minipigs to acquire an olfaction-based operant conditioning task and to determine the detection threshold for ethyl acetate and ethanol. We used an automated olfactometer developed for rodents to train and test 14 pigs. Odor sampling and reliable responding were obtained after three to fifteen 160-trial sessions. Successful transfer of the task from ethyl acetate to ethanol was achieved in 1–4 sessions. Detection threshold for ethyl acetate varied between 10−2% and 10−6% v/v and for ethanol between 0.1% and 5 × 10−6% v/v. The results provide evidence that minipigs can successfully acquire 2-odorant discrimination using a food-rewarded instrumental conditioning paradigm for testing olfactory function. This olfactory discrimination paradigm provides reliable measures of olfactory sensitivity and thereby enables detection of changes in olfaction in a porcine model of Alzheimer's disease currently being developed.

β-Adrenoceptor blockade depresses molecular and functional plasticities in the rat neocortex

β-Adrenergic receptor stimulation can significantly facilitate synaptic potentiation in the hippocampus and enhance memory processes, but its effect on neocortical plastic mechanisms is less conclusive. In the present study we determined the effect of propranolol, a β-adrenoceptor antagonist, on long-term potentiation (LTP) induced in vivo in rat occipital cortex by tetanizing stimulation of corpus callosum and observed a dose-dependent inhibition of LTP. We further administered propranolol through mini-osmotic pumps during 3 days, and observed the performance of rats in a complex operant conditioning learning paradigm and assessed the expression of brain-derived neurotrophic factor (BDNF) in the occipital cortex. Propranolol exposure depressed both the number of reinforced responses in the operant conditioning task and BDNF expression in occipital cortex. Taken together, our results suggest that propranolol impairs memory formation by inhibiting cortical LTP induction and associated BDNF expression.

Modulation of endothelial and neuronal nitric oxide synthases during learning of an operant conditioning task

Nitric oxide (NO) promotes plasticity and it is essential for learning, the NO synthases involved in these events are the endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) isoforms. The aim of this study was to study transcription, protein expression and enzymatic activity of eNOS and nNOS in the prefrontal cortex and the hippocampus during learning an operant conditioning task. Animals were considered incompletely trained (IT) when performed between 50% and 65% of responses, whereas animals were considered trained when reached 100% of responses with a latency time lower than 5 s. Following training session animals were killed and we quantified mRNA levels by Real Time RT-PCR, protein expression by western blot and enzymatic activity. eNOS and nNOS mRNA levels were only incremented in IT group. On the contrary, protein expression of both isoforms were augmented during all learning process. Moreover, we also found that eNOS and nNOS synthase activity were incremented in IT group and in trained group. Here, we showed that during learning there is a differential regulation of eNOS and nNOS in the prefrontal cortex and hippocampus and that NO could be acting as a promoter of plasticity.

Rapid shaping of behaviour associated with high urinary cortisol in domestic dogs

The occurrence of stress has widely been associated with impairments in learning abilities in animals, although the influence of stress appears to differ with the complexity of tasks. Previous research has suggested that some domestic dogs exhibit both physiological (elevated cortisol) and behavioural signs of stress when newly admitted to re-homing centres. In this study we have investigated whether levels of stress as measured by urinary cortisol: creatinine is sufficient to impair the learning of simple associations. On the day following their admission to a re-homing centre, 32 dogs were trained on one classical conditioning task and one operant conditioning task; 6 days later, they were trained on a second operant conditioning task. Their mean urinary cortisol:creatinine ratio (C/C) fell from 27.1 × 10 −6 to 22.3 × 10 −6 (nmol/l:nmol/l) between these 2 days; a substantial proportion (78% on day 1, 63% on day 7) of dogs had ratios above the range of 5–20 × 10 −6, which is that defined as clinically normal ( Bush, 1991), suggesting high levels of stress. The dogs’ average time to reach criterion on either task on day 1 was unrelated to C/C or to behavioural signs of stress; this lack of correspondence may reflect the diverse previous experiences of the dogs. On day 7, the six dogs which failed to reach criterion for the operant association were significantly less active and interactive in their kennels than the others. For the remainder, a high rate of learning the operant association was associated with high C/C (in excess of 40 × 10 −6), and a poor performance was associated with fearful behaviour in the kennel. Dogs appear to have adopted one of two coping strategies: either the display of fearful behaviours and an impaired ability to learn the tasks, which may reflect a ‘reactive’ style of responding, or a higher level of HPA axis activation and an enhanced ability to rapidly learn a new task, which may be indicative of a more ‘proactive’ coping style.

Female zebra finches prefer high-amplitude song

The intensity of a signal is crucial for animal communication because a high signal-to-noise ratio improves signal reception. However, variation in amplitude may also have signalling value. In songbirds, song amplitude varies considerably between males but little is known about the causes and consequences of this variation. One of the main functions of birdsong is mate attraction, but whether and how amplitude variation (beyond reception thresholds) affects female choice at all is poorly understood, as this parameter is notoriously difficult to measure in the field. However, levels of signal amplitude at the source and at the receiver's end can be reliably controlled under laboratory conditions. Here we addressed the question whether differences in male song amplitude may influence female choice. Song preferences of female zebra finches, Taeniopygia guttata, were tested in an operant conditioning task involving sets of four song stimuli, in each case derived from one original song. Within a set, stimuli differed in amplitude or in level of degradation but not in song phonology or syntax. We found that females preferred songs with higher sound pressure level within the tested range of naturally observed amplitude variation regardless of the two reverberation levels. As song preferences are highly predictive of mate choice in this species, our results suggest that female zebra finches may use song amplitude as a criterion in mate choice. This raises the question what information the naturally occurring variation in amplitude between males in this and other songbird species conveys about the singer.

Plasticity in the Rat Prefrontal Cortex: Linking Gene Expression and an Operant Learning with a Computational Theory

The plasticity in the medial Prefrontal Cortex (mPFC) of rodents or lateral prefrontal cortex in non human primates (lPFC), plays a key role neural circuits involved in learning and memory. Several genes, like brain-derived neurotrophic factor (BDNF), cAMP response element binding (CREB), Synapsin I, Calcium/calmodulin-dependent protein kinase II (CamKII), activity-regulated cytoskeleton-associated protein (Arc), c-jun and c-fos have been related to plasticity processes. We analysed differential expression of related plasticity genes and immediate early genes in the mPFC of rats during learning an operant conditioning task. Incompletely and completely trained animals were studied because of the distinct events predicted by our computational model at different learning stages. During learning an operant conditioning task, we measured changes in the mRNA levels by Real-Time RT-PCR during learning; expression of these markers associated to plasticity was incremented while learning and such increments began to decline when the task was learned. The plasticity changes in the lPFC during learning predicted by the model matched up with those of the representative gene BDNF. Herein, we showed for the first time that plasticity in the mPFC in rats during learning of an operant conditioning is higher while learning than when the task is learned, using an integrative approach of a computational model and gene expression.