Discrimination Learning In Rats Research Articles

Abstract numerical discrimination learning in rats.

In this study, we examined rats' discrimination learning of the numerical ordering positions of objects. In Experiments 1 and 2, five out of seven rats successfully learned to respond to the third of six identical objects in a row and showed reliable transfer of this discrimination to novel stimuli after being trained with three different training stimuli. In Experiment 3, the three rats from Experiment 2 continued to be trained to respond to the third object in an object array, which included an odd object that needed to be excluded when identifying the target third object. All three rats acquired this selective-counting task of specific stimuli, and two rats showed reliable transfer of this selective-counting performance to test sets of novel stimuli. In Experiment 4, the three rats from Experiment 3 quickly learned to respond to the third stimulus in object rows consisting of either six identical or six different objects. These results offer strong evidence for abstract numerical discrimination learning in rats.

Analysis of the Acquisition of Drug Discrimination Reveals Differences Between a High Versus Low Training Dose of ±3,4-methylenedioxymethamphetamine (MDMA)

Background. Studies of the discriminative stimulus effects of the recreational drug, ±3,4- methylenedioxymethamphetamine (MDMA), typically use a dose of 1.5 mg/kg during training. This dose is relatively low compared to those used in other behavioral paradigms. Purpose. The present study assessed the ability of this low dose of MDMA and a higher dose of 3.0 mg/kg to support drug- discrimination learning in rats. Procedures. Daily training sessions were preceded by an injection of either MDMA (1.5 mg/kg or 3.0 mg/kg) or saline. Injections alternated in a pseudorandom fashion for a total of 63 sessions. Criteria for the acquisition of the MDMA/saline discrimination were increased from 4 to 10 successive, and successful, discriminations. As the acquisition criteria became more stringent, the impact on the low dose discrimination was greater than the impact on the high dose discrimination. Conclusions. These results suggest that the drug discrimination produced by 1.5 mg/kg MDMA may be less reliable than when a higher dose is employed, especially when the number of training sessions is limited. The data further suggest that 3.0 mg/kg MDMA produced a robust discriminative stimulus effect which may be better suited to experiments of this nature.

Positive and negative feedback learning and associated dopamine and serotonin transporter binding after methamphetamine

Learning from mistakes and prospectively adjusting behavior in response to reward feedback is an important facet of performance monitoring. Dopamine (DA) pathways play an important role in feedback learning and a growing literature has also emerged on the importance of serotonin (5HT) in reward learning, particularly during punishment or reward omission (negative feedback). Cognitive impairments resulting from psychostimulant exposure may arise from altered patterns in feedback learning, which in turn may be modulated by DA and 5HT transmission. We analyzed long-term, off-drug changes in learning from positive and negative feedback and associated striatal DA transporter (DAT) and frontocortical 5HT transporter (SERT) binding in rats pretreated with methamphetamine (mAMPH). Specifically, we assessed the reversal phase of pairwise visual discrimination learning in rats receiving single dose- (mAMPHsingle) vs. escalating-dose exposure (mAMPHescal). Using fine-grained trial-by-trial analyses, we found increased sensitivity to and reliance on positive feedback in mAMPH-pretreated animals, with the mAMPHsingle group showing more pronounced use of this type of feedback. In contrast, overall negative feedback sensitivity was not altered following any mAMPH treatment. In addition to validating the enduring effects of mAMPH on early reversal learning, we found more consecutive error commissions before the first correct response in mAMPH-pretreated rats. This behavioral rigidity was negatively correlated with subregional frontocortical SERT whereas positive feedback sensitivity negatively correlated with striatal DAT binding. These results provide new evidence for the overlapping, yet dissociable roles of DA and 5HT systems in overcoming perseveration and in learning new reward rules.

Sleep enhances inhibitory behavioral control in discrimination learning in rats.

Sleep supports the consolidation of memory, and it has been proposed that this enhancing effect of sleep pertains in particular to memories which are encoded under control of prefrontal–hippocampal circuitry into an episodic memory system. Furthermore, repeated reactivation and transformation of such memories during sleep are thought to promote the de-contextualization of these memories. Here, we aimed to establish a behavioral model for the study of such sleep-dependent system consolidation in rats, using a go/nogo conditional discrimination learning task known to essentially depend on prefrontal–hippocampal function. Different groups of rats were trained to criterion on this task and, then, subjected to 80-min retention intervals filled with spontaneous morning sleep, sleep deprivation, or spontaneous evening wakefulness. In a subsequent test phase, the speed of relearning of the discrimination task was examined as indicator of memory, whereby rats were either tested in the same context as during training or in a different context. Sleep promoted relearning of the conditional discrimination task, and this effect was similar for testing memory in the same or different context (p < 0.001). Independent of sleep and wakefulness during the retention interval, animals showed faster relearning when tested in the same context as during learning, compared with testing in a different context (p < 0.001). The benefitting effect of sleep on discrimination learning was primarily due to an enhancing effect on response suppression during the nogo stimulus. We infer from these results that sleep enhances memory for inhibitory behavioral control in a generalized context-independent manner and thereby might eventually also contribute to the abstraction of schema-like representations.

Odor preferences shape discrimination learning in rats.

Forced-choice discrimination is a standard behavioral paradigm used to test animals' abilities in learning and memory. In this type of task, a reward association is made between a sensory stimulus and a food or water reward and the frequency of correct choice for the stimulus associated with the reward is measured. We show here that when olfactory sensory stimuli are used, spontaneous preferences for odors can influence speed of acquisition in a forced-choice discrimination task. We first show that among a battery of 53 odorants, some odorants elicit longer bouts of spontaneous investigation than others. By measuring relative spontaneous investigation times for pairs of simultaneously presented odorants, we confirm that these odor preferences are robust and reliable. Finally, we show that performance on a forced-choice olfactory discrimination task depends on relative spontaneous preferences between the rewarded and unrewarded odorants. Namely, rats acquire novel forced-choice odor discrimination problems significantly faster if the preferred odorant, as assessed by relative spontaneous investigation time, is associated with the reward. These results indicate that even subtle differences in the tendency for an animal to approach and investigate one odorant over another can lead to substantial biases in basic learning and memory tasks.

Isoflurane impairs odour discrimination learning in rats: differential effects on short- and long-term memory

Anaesthetics suppress the formation of lasting memories at concentrations that do not suppress perception, but it is unclear which elements of the complex cascade leading from a conscious experience to a lasting memory trace are disrupted. Experiments in conscious humans suggest that subhypnotic concentrations of anaesthetics impair consolidation or maintenance rather than acquisition of a representation (long-term more than short-term memory). We sought to test whether these agents similarly impair learning in rats. We used operant conditioning in rats to examine the effect of isoflurane on acquisition compared with long-term (24 h) memory of non-aversive olfactory memories using two different odour discrimination tasks. Rats learned the 'valences' of odour pairs presented either separately (task A) or simultaneously (task B), under control conditions and under isoflurane inhalation. In a separate set of experiments, we tested the ability of the animals to recall a learning set that had been acquired 24 h previously. Under 0.4% isoflurane inhalation, the average number of trials required to reach criterion performance (18 correct responses in 20 successive trials) increased from 21.9 to 43.5 (P<0.05) and 24.2 to 54.4 (P<0.05) for tasks A and B, respectively. Under 0.3% isoflurane inhalation, only task B was impaired (from 24.2 to 31.5 trials, P<0.05). Recall at 24 h was dose-dependently impaired or prevented by isoflurane for both tasks. Isoflurane interfered with long-term memory of odour valence without preventing its acquisition. This paradigm may serve as a non-aversive animal model of conscious amnesia.

Muscimol, AP5, or scopolamine infused into perirhinal cortex impairs two-choice visual discrimination learning in rats

The perirhinal cortex (PRh) has been strongly implicated in object recognition memory and visual stimulus representation. Studies of object recognition have revealed evidence for the involvement of several neurotransmitter subsystems, including those involving NMDA ( N-methyl- d-aspartic acid) and muscarinic cholinergic receptors. In the present study, we assessed the possible involvement of PRh and related receptor subsystems in two-choice visual discrimination learning by Lister Hooded rats tested in touchscreen-equipped operant boxes. In Experiment 1, daily pre-training inactivation of PRh with the GABA A receptor agonist muscimol (0.5 μg/hemisphere) significantly impaired acquisition of the two-choice visual discrimination. In Experiment 2, daily pre-training blockade of either NMDA or muscarinic receptors in PRh with AP5 (5.9 μg/hemisphere) or scopolamine (10 μg/hemisphere), respectively, impaired task acquisition. These results parallel the findings from object recognition studies and suggest a generality of neurotransmitter receptor involvement underlying the role of PRh in both object recognition memory and visual discrimination learning. The involvement of PRh in both types of tasks may be related to its role in complex visual stimulus representation.

ENSEMBLE RECORDINGS IN AWAKE RATS: ACHIEVING BEHAVIORAL REGULARITY DURING MULTIMODAL STIMULUS PROCESSING AND DISCRIMINATIVE LEARNING

To meet an increasing need to examine the neurophysiological underpinnings of behavior in rats, we developed a behavioral system for studying sensory processing, attention and discrimination learning in rats while recording firing patterns of neurons in one or more brain areas of interest. Because neuronal activity is sensitive to variations in behavior which may confound the identification of neural correlates, a specific aim of the study was to allow rats to sample sensory stimuli under conditions of strong behavioral regularity. Our behavioral system allows multimodal stimulus presentation and is coupled to modules for delivering reinforcement, simultaneous monitoring of behavior and recording of ensembles of well isolated single neurons. Using training protocols for simple and compound discrimination, we validated the behavioral system with a group of 4 rats. Within these tasks, a majority of medial prefrontal neurons showed significant firing-rate changes correlated to one or more trial events that could not be explained from significant variation in head position. Thus, ensemble recordings can be combined with discriminative learning tasks under conditions of strong behavioral regularity.

Dopaminergic modulation of olfactory bulb processing affects odor discrimination learning in rats.

Olfactory behavioral studies have shown that, when modulated through systemic injections, D1 and D2 receptors have opposing effects on odor discrimination learning. In the present study, cannulated male Sprague-Dawley rats were used to investigate how the modulation of these 2 types of dopaminergic receptors through direct infusion of D1/D2 agonists and antagonists into the olfactory bulb affect olfactory perception. Dopaminergic modulation was locally altered by manipulations of D1 (agonist SKF 82958: 14.6, 43.8, & 143.6 mM; antagonist SCH-23390: 13.4, 40.1, & 60.1 mM) and D2 (agonists quinpirole: 78.2, 117.3, & 156.4 mM; antagonist sulpiride: 0.3, 0.9, & 2.9 mM) receptors during a simultaneous odor discrimination task. The authors found that modulation of D2, but not D1, receptors significantly affected rats' odor discrimination performance. A significant positive correlation between blockade of D2 receptors and discrimination performance, as well as a significant negative correlation between D2 receptor activation and discrimination performance, was observed.

Contextual conditional discriminations

Three experiments used a discriminated operant procedure to study conditional discrimination learning in rats. The first experiment showed that rats were capable of learning a biconditional discrimination in which two contexts served as conditional cues signalling the reinforcement contingencies associated with two discriminative stimuli. The discrimination was learned equally well when one discriminative stimulus signalled food, the other its absence, and when one stimulus signalled food, the other extinction plus mild footshock. In Experiment 2 it was shown that prior training on such a conditional discrimination enhanced the subsequent context specificity of simple conditioning relative to control groups of animals for whom the prior training had not been conditional. Experiment 3 showed that a reversal of the significance of one pair of discriminative stimuli produced no spontaneous reversal in performance to a second, target, pair. The pattern of results is best accounted for by an analysis of contex...

The brain metabolic enhancer methylene blue improves discrimination learning in rats

Methylene blue (MB) is a metabolic enhancer that has been demonstrated to improve memory retention when given post-training in low doses in a variety of tasks in rats, including inhibitory avoidance, spatial memory (in both normal and metabolically-impaired subjects), object recognition, and habituation to a familiar environment. MB has been also shown to improve memory retention of extinction of fear conditioning in the rat. No experiments have been conducted to determine the effects of MB on more complex learning such as in discrimination tasks that require repeated days of training. This study examined the effects of daily MB on spatial discrimination memory in a baited holeboard maze. Following three days of discrimination training, subjects treated daily with post-training MB (1 mg/kg) reliably discriminated between rewarded (baited) and non-rewarded (unbaited) trials as indicated by a greater number of correct responses on rewarded trials than non-rewarded trials during the last three days of discrimination training. No such discrimination effects were observed in the saline-treated control group during the same training period. To determine whether the memory-enhancing effects of MB are associated with an increase in metabolic energy capacity in the brain, cytochrome c oxidation was measured in brains from rats treated with 1 mg/kg MB or saline for three days. The number of daily injections was chosen based on the behavioral data which revealed group differences three days after the beginning of MB treatment. Brain cytochrome oxidase activity in the MB-treated group was approximately 70% higher than in saline-treated rats. The findings suggest that repeated post-training MB may improve memory consolidation between days of learning by an induction in the enzyme cytochrome oxidase, leading to increased metabolic capacity in brain regions requiring more energy during discrimination learning.

Endogenous fluorescence imaging of somatosensory cortical activities after discrimination learning in rats

Aerobic energy metabolism in the brain is reflected as changes in the green fluorescence of mitochondrial flavoproteins, and the activity-dependent changes in endogenous fluorescence are applicable for functional brain imaging. To understand the roles of cortical plasticity in discrimination learning, we used flavoprotein fluorescence imaging to visualize changes of neural activities in the rat primary somatosensory cortex (SI) after learning. Rats were trained to discriminate floor vibration at rewarded and unrewarded frequencies. After this discrimination learning was accomplished in 3–5 days, the rats were anesthetized with urethane (1.5 g/kg, i.p.), and neural responses were recorded in SI during flutter stimuli applied to the contralateral hindpaw. The fluorescence responses to the stimuli at unrewarded frequencies were selectively depressed in the trained rats, which had behaviorally neglected unrewarded stimuli. The depression of cortical responses was not observed in the rats trained with rewarded stimuli only. Therefore, the stimulus-specific depression in SI might explain a part of neural mechanisms underlying discrimination behavior. To reproduce the stimulus-specific depression of cortical responses in anesthetized rats, tetanic cortical stimulation was paired with flutter stimulation applied to the hindpaw. Selective depression of fluorescence responses or field potentials in SI was induced by the paired stimulation. Our findings suggest that some intracortical circuits in SI are specifically tuned to and modulated by unrewarded stimuli of a particular frequency while SI neurons are responsive to both of rewarded and unrewarded stimuli. The present results indicate the usefulness of flavoprotein fluorescence imaging for investigating somatosensory cortical plasticity after learning.

Visual discrimination learning in rats with striatal kainic acid lesions

Intrastriatal kainic acid (KA) administration induces selective neuronal cell death in the striatum sparing passing nerve fibers and terminals. Although performance deficits of several kinds of learning tasks have been reported in striatal KA-lesioned rats, the problem remains unsolved whether these animals can discriminate visual stimuli to acquire such learning tasks. This study investigated, therefore, the effects of intrastriatal KA administration on the acquisition of vertical vs. horizontal stripe discrimination learning. Striatal KA-lesioned rats did not show any deficit in the process of learning this task in comparison with vehicle-treated control rats. Results suggest that learning deficits that have been reported in animals with a loss of striatal neurons cannot be explained by deficits of visual discrimination ability such as measured in this study.

Conditional discrimination learning in rats with global ischaemic brain damage

Hippocampal cell loss was induced by the four-vessel occlusion (4VO) method, a model of global ischaemia. Global ischaemia for 15 min induced a selective damage to the CA1 subfield. Occlusion for 25 min produced a larger cell loss within the CA1 and more variably the CA2, CA3, the striatum and cortex. Ischaemic and sham control groups were assessed on two conditional discrimination tasks (presenting the conditional cues either in the choice arms or the start arm) and two spatial tasks (water maze and a simple spatial discrimination task). No significant effects were found on either of the spatial tasks (apart from the speed measure on the water maze). However, on the conditional discrimination task with the cues in the choice arms, animals with 25 min ischaemia learned the task significantly more slowly than the 15 min ischaemic and control groups. Results for the task with cues presented in the start arm differed according to choice of criterion for learning. With a standard criterion of 90% accuracy on one session controls were significantly superior to both ischaemic groups. However, in this task rats with 15 min occlusion showed the greatest impairment, and were significantly worse than both the controls and the 25 min occlusion group. These results suggest that hippocampal ischaemic damage disrupts the learning of conditional discrimination but not simple spatial tasks. No clear relationship between the extent of hippocampal cell loss and behavioural impairment was evident. These results highlight the critical importance of procedural factors in the assessment of cognitive impairment.

Chronic Moderate Hyperammonemia Impairs Active and Passive Avoidance Behavior and Conditional Discrimination Learning in Rats

The cerebral dysfunction associated with hepatic encephalopathy is generally considered to have hyperammonemia as one of its main causes. Hyperammonemia impairs the neuronal glutamate–nitric oxide–cyclic GMP pathway and the induction of NMDA receptor-dependent long-term potentiation in the hippocampus. We studied the performance of pre/neonatally and postnatally exposed rats to hyperammonemia on active avoidance, passive avoidance, and conditional discrimination tasks. Pre/neonatal hyperammonemia slowed learning of active avoidance behaviors and impaired memory for the passive avoidance task while postnatal hyperammonemia impaired learning on the conditional discrimination task. Hyperammonemia thus may produce cognitive disturbances that relate to the effects of ammonia on the neuronal glutamate–nitric oxide–cyclic GMP pathway.

Restricted lesions to ventral prefrontal subareas block reversal learning but not visual discrimination learning in rats

LI, L. AND J. SHAO. Restricted lesions to ventral prefrontal subareas block reversal learning but not visual discrimination learning in rats. PHYSIOL BEHAV 65(2) 371–379, 1998.—Previous studies have shown that extensive damage to the medial prefrontal cortex (mPFC) of rats causes reversal learning deficits. The mPFC of rats, however, consists of several subareas that are different from each other in both cytoarchitecture and neural connectivity, suggesting a functional dissociation among the mPFC subareas. In the present study, selective lesions of the mPFC of rats were made with a specially designed microknife whose intracranial placement could be controlled stereotaxically. Restricted lesions were made to each of the 3 parts of the mPFC: the anterior cingulate area (AC) (including the medial precentral area, PrCm), the prelimbic area (PL), and the infralimbic area (IL). One week after surgery, rats were trained in an aversively motivated visual discrimination task in a novel rotating T-maze. After reaching the acquisition criterion, rats were trained in a reversal task in the same maze. No difference was found in acquisition between control and mPFC lesioned rats. However, lesions of either the PL or the IL produced a marked deficit in the reversal task. This behavioral deficit was not found in rats with lesions of the AC. The results indicate that the mPFC of rats is not essential for discrimination learning, but that each of the 2 ventral subareas of the mPFC, PL, and IL, plays a critical role in reversal learning.

P-82 - Effects of hippocampal lesions to the lever-press responses on the discrimination learning in rat

P-82 - Effects of hippocampal lesions to the lever-press responses on the discrimination learning in rat

Rhinal cortex lesions impair simultaneous olfactory discrimination learning in rats.

Previous studies have found that combined lesions of the perirhinal and entorhinal (PRER) cortical areas do not impair, and in fact may facilitate, acquisition of successive olfactory discriminations. The present study sought to determine the effect of PRER lesions on the acquisition of simultaneous olfactory discriminations. Rats (N = 24; 9 PRER-lesioned, 15 sham-operated controls) were trained on a single simultaneous olfactory discrimination; PRER-lesioned animals were dramatically and persistently impaired in acquisition of the discrimination relative to sham-operated subjects. These data are consistent with the view that, in concert with the hippocampus, these cortical regions participate in the encoding of relations among multiple extant stimuli.

Rhinal cortex lesions impair simultaneous olfactory discrimination learning in rats.

Previous studies have found that combined lesions of the perirhinal and entorhinal (PRER) cortical areas do not impair, and in fact may facilitate, acquisition of successive olfactory discriminations. The present study sought to determine the effect of PRER lesions on the acquisition of simultaneous olfactory discriminations. Rats (N = 24; 9 PRER-lesioned, 15 sham-operated controls) were trained on a single simultaneous olfactory discrimination; PRER-lesioned animals were dramatically and persistently impaired in acquisition of the discrimination relative to sham-operated subjects. These data are consistent with the view that, in concert with the hippocampus, these cortical regions participate in the encoding of relations among multiple extant stimuli.

O-256 - Effects of NG-nitro-L-arginine methyl ester on discrimination learning in rats

O-256 - Effects of NG-nitro-L-arginine methyl ester on discrimination learning in rats