Object Discrimination Task Research Articles

Effects of a neurotensin analogue (PD149163) and antagonist (SR142948A) on the scopolamine-induced deficits in a novel object discrimination task

Various lines of evidence suggest a role in cognition for the endogenous neuropeptide, neurotensin, involving an interaction with the central nervous system cholinergic pathways. A preliminary study has shown that central administration of neurotensin enhances spatial and nonspatial working memory in the presence of scopolamine, a muscarinic receptor antagonist which induces memory deficits. Utilizing similar methods, the present study employed a two-trial novel object discrimination task to determine the acute effect of a neurotensin peptide analogue with improved metabolic stability, PD149163, on recognition memory in Lister hooded rats. Consistent with previous findings with neurotensin, animals receiving an intracerebroventricular injection of PD149163 (3 microg) significantly discriminated the novel from familiar object during the choice trial. In addition, a similar dose of PD149163 restored the scopolamine-induced deficit in novelty recognition. The restoration effect on scopolamine-induced amnesia produced by PD149163 was blocked by SR142948A, a nonselective neurotensin receptor antagonist, at a dose of 1 mg/kg (intraperitonial) but not at 0.1 mg/kg. In conclusion, the present results confirm a role for neurotensin in mediating memory processes, possibly via central cholinergic mechanisms.

Evidence for the importance of basal ganglia output nuclei in semantic event sequencing: An fMRI study

Semantic event sequencing is the ability to plan ahead and order meaningful events chronologically. To investigate the neural systems supporting this ability, an fMRI picture sequencing task was developed. Participants sequenced a series of four pictures presented in random order based on the temporal relationship among them. A control object discrimination task was designed to be comparable to the sequencing task regarding semantic, visuospatial, and motor processing requirements but without sequencing demands. fMRI revealed significant activation in the dorsolateral prefrontal cortex and globus pallidus internal part in the picture sequencing task compared with the control task. The findings suggest that circuits involving the frontal lobe and basal ganglia output nuclei are important for picture sequencing and more generally for the sequential ordering of events. This is consistent with the idea that the basal ganglia output nuclei are critical not only for motor but also for high-level cognitive function, including behaviors involving meaningful information. We suggest that the interaction between the frontal lobes and basal ganglia output nuclei in semantic event sequencing can be generalized to include the sequential ordering of behaviors in which the selective updating of neural representations is the key computation.

Functional Specialization in the Human Medial Temporal Lobe

Investigations of memory in rats and nonhuman primates have demonstrated functional specialization within the medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampal formation and underlying entorhinal, perirhinal, and parahippocampal cortices. Most studies in humans, however, especially in patients with brain damage, suggest that the human MTL is a unitary memory system supporting all types of declarative memory, our conscious memory for facts and events. To resolve this discrepancy, amnesic patients with either selective hippocampal damage or more extensive MTL damage were tested on variations of an object discrimination task adapted from the nonhuman primate literature. Although both groups were equally impaired on standard recall-based memory tasks, they exhibited different profiles of performance on the object discrimination test, arguing against a unitary view of MTL function. Cases with selective hippocampal damage performed normally, whereas individuals with broader MTL lesions were impaired. Furthermore, deficits in this latter group were related not to the number of discriminations to be learned and remembered, but to the degree of "feature ambiguity," a property of visual discriminations that can emerge when features are part of both rewarded and unrewarded stimuli. These findings resolve contradictions between published studies in humans and animals and introduce a new way of characterizing the impairments that arise after damage to the MTL.

Robust habit learning in the absence of awareness and independent of the medial temporal lobe

Habit memory is thought to involve slowly acquired associations between stimuli and responses and to depend on the basal ganglia. Habit memory has been well studied in experimental animals but is poorly understood in humans because of their strong tendency to acquire information as conscious (declarative) knowledge. Here we show that humans have a robust capacity for gradual trial-and-error learning that operates outside awareness for what is learned and independently of the medial temporal lobe. We tested two patients with large medial temporal lobe lesions and no capacity for declarative memory. Both patients gradually acquired a standard eight-pair object discrimination task over many weeks but at the start of each session could not describe the task, the instructions or the objects. The acquired knowledge was rigidly organized, and performance collapsed when the task format was altered.

Developmental Study of the Hippocampal Formation in Rhesus Monkeys (Macaca mulatta): I. Early Ablations Spare Discrimination Learning but Not Recognition Memory.

In clinical cases of amnesia that followed bilateral excisions of medial temporal lobe structures, with some perceptual learning abilities intact, damage to the hippocampus was presumed to be the critical factor. The authors' search for an animal model of amnesia, based on ablations aimed at the hippocampal formation in infant rhesus monkeys, provides support for this view. Ablations of the hippocampal formation in 2-month-old infants tested shortly after recovery from surgery resulted in a deficit on a recognition memory task but left intact the ability to learn the concurrent object discrimination task, even though the latter task was administered with the use of a massed practice procedure. Thus, early damage, unlike that at 2 years of age or later, allowed the authors to dissociate associative learning with repeated trials, independent of hippocampal functions and recognition memory that depends on the integrity of the hippocampus.

Carbamazepine Enhances Discriminative Memory in a Rat Model of Epilepsy

Seizures and antiepileptic drugs (AEDs) are the main causes for cognitive impairment in persons with epilepsy. It is still a matter of debate whether carbamazepine (CBZ) improves cognition because of its own psychotropic effects or because it is more effective to treat temporal epilepsy. Our objective was to analyze the performance of CBZ-treated or nontreated pilocarpine epileptic rats in an object-recognition test. Twelve chronic pilocarpine-induced epileptic rats were treated with CBZ, 40 mg/kg, or saline, t.i.d. for 8 days. Twenty-one nonepileptic controls were treated with CBZ or saline. On day 8 of treatment, all rats were tested with an object-recognition paradigm. No locomotor impairment was detected in chronic epilepsy or CBZ treatment, as exploration during training was not affected. Exploratory behaviors during the choice session were not decreased in rats treated with CBZ; therefore CBZ does not compromise procedural memory. Epileptic rats showed a nonsignificant change in the discrimination performance, and prolonged treatment with CBZ in epileptic rats induced a significant increase in object discrimination during the choice session. Even though pilocarpine-induced epileptic animals do not show compromised performance in the spontaneous object-recognition test, prolonged CBZ treatment has a positive effect on a simple object-discrimination task. These results may be associated with the psychotropic effects of CBZ.

5-HT 6 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing consolidation—an effect sensitive to NMDA receptor antagonism

5-HT 6 receptors are expressed in brain regions associated with learning and memory, and blockade of their function increases central cholinergic and glutamatergic neurotransmission and enhances cognitive processes. This study examined the effects of acute systemic administration of two selective 5-HT 6 receptor antagonists Ro 04-6790 and SB-271046 (10 mg kg −1 i.p.) on acquisition, consolidation, and retrieval in the novel object discrimination (NOD) task, a two-trial test of recognition memory in which rats exposed to two identical objects during a familiarisation trial can discriminate a novel from a familiar object during the subsequent choice trial, following inter-trial delays of up to 3 h. 5-HT 6 receptor antagonist administration 20 min prior to or immediately after the familiarisation trial, but not 20 min prior to the choice trial reversed the deficit in object discrimination produced by a 4 h inter-trial interval. The nootropic effects of the 5-HT 6 receptor antagonists in this task thus appear to involve enhanced consolidation. Pre-treatment with the non-competitive NMDA receptor antagonist MK-801 (0.05 mg kg −1 i.p.) prevented the effect of Ro 04-6790 on delay-induced deficits in object discrimination. This suggests that the 5-HT 6 receptor antagonist-induced enhancement of consolidation involves increased central glutamatergic neurotransmission.

5-HT6 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing consolidation?an effect sensitive to NMDA receptor antagonism

5-HT 6 receptors are expressed in brain regions associated with learning and memory, and blockade of their function increases central cholinergic and glutamatergic neurotransmission and enhances cognitive processes. This study examined the effects of acute systemic administration of two selective 5-HT 6 receptor antagonists Ro 04-6790 and SB-271046 (10 mg kg −1 i.p.) on acquisition, consolidation, and retrieval in the novel object discrimination (NOD) task, a two-trial test of recognition memory in which rats exposed to two identical objects during a familiarisation trial can discriminate a novel from a familiar object during the subsequent choice trial, following inter-trial delays of up to 3 h. 5-HT 6 receptor antagonist administration 20 min prior to or immediately after the familiarisation trial, but not 20 min prior to the choice trial reversed the deficit in object discrimination produced by a 4 h inter-trial interval. The nootropic effects of the 5-HT 6 receptor antagonists in this task thus appear to involve enhanced consolidation. Pre-treatment with the non-competitive NMDA receptor antagonist MK-801 (0.05 mg kg −1 i.p.) prevented the effect of Ro 04-6790 on delay-induced deficits in object discrimination. This suggests that the 5-HT 6 receptor antagonist-induced enhancement of consolidation involves increased central glutamatergic neurotransmission.

Effect of unilateral temporal lobe resection on short-term memory for auditory object and sound location.

To investigate auditory spatial and nonspatial short-term memory, a sound location discrimination task and an auditory object discrimination task were used in patients with medial temporal lobe resection. The results showed a double dissociation between the side of the medial temporal lobe lesion and the nature of the auditory discrimination deficits, suggesting that right and left temporal lobe structures are differently involved in auditory spatial and nonspatial short-term memory.

Reversal of a cholinergic-induced deficit in a rodent model of recognition memory by the selective 5-HT6 receptor antagonist, Ro 04-6790.

Accumulating evidence suggests a potential role for the 5-HT(6 )receptor in cognitive function and the potential use of 5-HT(6) receptor antagonists in the treatment of learning and memory disorders. The aim of the current study was to investigate the effect of the selective 5-HT(6) receptor antagonist, Ro 04-6790, on both the performance of normal adult rats and restoration of a pharmacological disruption of memory function produced by the non-selective muscarinic receptor antagonist, scopolamine, or the dopamine D(2) receptor antagonist, raclopride, in a rodent model of recognition memory. Passive, perceptually based, recognition memory was assessed using a novel object discrimination task. Following habituation to an arena, rats were presented with two identical objects during trial 1 (T(1)) and a novel and familiar object during trial 2 (T(2)). The time spent exploring the two objects in each trial was measured and novel object discrimination assessed in T(2). In the absence of drug all rats spent an equal time exploring the two identical objects in T(1) but more time exploring the novel object in T(2). Scopolamine (but not N-methylscopolamine) and raclopride both produced a dose-dependent reduction in novel object discrimination whilst the 5-HT(6) receptor antagonist, Ro 04-6790, had no effect on discrimination when given alone but completely reversed the scopolamine- but not the raclopride-induced deficit. This study demonstrates that acute administration of Ro 04-6790 reverses a cholinergic but not a dopaminergic deficit in a rodent model of recognition memory and provides further support for a role of the 5-HT(6) receptor in the regulation of cognitive function.

Unilateral hippocampal and inferotemporal cortex lesions in opposite hemispheres impair learning of single-pair visual discriminations as well as visuovisual conditional tasks in monkeys

Monkeys with unilateral ablations of the inferotemporal (IT) cortex were not impaired on learning or retention of single-pair object discriminations or visuovisual conditional tasks. Addition of an excitotoxic hippocampal lesion to the hemisphere opposite to the IT ablation impaired retention and acquisition of single-pair object discriminations and visuovisual conditional tasks. Histology revealed no areas of bilaterally symmetrical damage. Previous experiments have shown that bilateral excitotoxic hippocampal lesions do not impair single-pair object discriminations although they do produce a substantial impairment on visuovisual conditional tasks. Bilateral IT ablations produce impairment on single-pair object discrimination tasks. It is argued that the hippocampus in the hemisphere with the IT ablation is deprived of feed-forward visual input and that this, in addition to the contralateral hippocampal lesion, accounts for the impairment on the visuovisual conditional tasks. It is also argued that feed-back projections from the hippocampus to the IT cortex influence the learning of single-pair object discriminations. This influence may be difficult to demonstrate by the addition of hippocampal lesions to IT lesions because of the substantial effect of the IT lesion alone. It may be difficult to demonstrate by bilateral hippocampal lesions alone since the effect may be below that which generates an observable impairment. Nonetheless, an effect may be seen when a hippocampal lesion is made in monkeys with some IT damage, as in this experiment, as well as by the general observation that large lesions of the temporal lobes produce larger perceptuo-mnemonic impairments than lesions confined to the hippocampus or temporal neocortex in monkeys and man.

Crossed unilateral lesions of temporal lobe structures and cholinergic cell bodies impair visual conditional and object discrimination learning in monkeys.

Monkeys with excitotoxic lesions of the CA1/subiculum region in the right hemisphere and with immunotoxic lesions of the cholinergic cells of the diagonal band in the left hemisphere were impaired on a visual conditional task. In this task, correct choice of one of two objects depends on which of two background fields both objects are presented against, irrespective of the spatial positions of the objects. They were not impaired on simple object or shape discrimination tasks. The pattern of impairments is the same as that seen after bilateral excitotoxic lesions of CA1/subiculum, implying that the diagonal band lesion disables the ipsilateral CA1/subiculum. It also argues that CA1/subiculum, sustained by its cholinergic input, is necessary for some forms of nonspatial conditional learning. Addition of an inferotemporal (IT) cortical ablation to the left hemisphere did not affect simple visual discrimination learning, although all the monkeys then failed to learn a new visual conditional task. This demonstrates that intact IT cortex in only one hemisphere is sufficient to sustain simple visual discrimination learning but implies that the cholinergic input and the inferotemporal cortical input to the hippocampus both contribute to visual conditional learning. The subsequent addition of an immunotoxic lesion of the basal nucleus of Meynert in the right hemisphere resulted in an additional impairment on a difficult shape discrimination. This argues that it is the cholinergic projection to the inferotemporal cortex, rather than to the rest of the cortex, which contributes to visual discrimination learning and memory.

Dissociation in retrograde memory for object discriminations and object recognition in rats with perirhinal cortex damage

This experiment examined the effects of perirhinal cortex (PeRh) lesions on rats’ retrograde memory for object-discriminations and retrograde object recognition. Rats learned one discrimination problem or five concurrent discrimination problems 4 weeks before surgery, and a new problem or five new problems during the week preceding surgery. Each rat was also familiarized with a sample object in an open field, 5, 3, or 1 week before surgery. PeRh-lesioned rats displayed normal retention of the object discrimination problems, but on a test of novelty preference they showed evidence of impaired recognition of the sample objects. A similar dissociation was observed on anterograde tests of object-discrimination learning and object recognition. The findings suggest the perirhinal cortex plays an essential role in rats’ ability to discriminate the familiarity of objects previously encountered either before or after surgery, but this ability may not be essential for accurate performance of a simple object-discrimination task.

Discriminative whisking in the head-fixed rat: optoelectronic monitoring during tactile detection and discrimination tasks

We compared whisking movement patterns during acquisition of tactile detection and object discrimination under conditions in which (a) head movements are excluded and (b) exposure to tactile discriminanda is confined to the large, moveable vibrissae (macrovibrissae). We used optoelectronic instrumentation to track the movements of an individual whisker with high spatio-temporal resolution and a testing paradigm, which allowed us to dissociate performance on an “indicator” response (lever pressing) from the rat's “observing” responses (discriminative whisking). We analyzed the relation between discrimination performance and whisking movement patterns in order to clarify the process by which the indicator response comes under the stimulus control of information acquired by the rat's whisking behavior. Whisking patterns over the course of task acquisition differed with task demands. Acquisition of the Detection task was correlated with modulation of only one whisking movement parameter - total number of whisks emitted, and more whisking was seen on trials in which the discriminandum was absent. Discrimination between a sphere and cube differing in size and texture was correlated with a reduction in whisk duration and protraction amplitude and with a shift towards higher whisking frequencies. Our findings confirm previous reports that acquisition of tactile discriminations involves modulation by the animal of both the amount and the type of whisking. In contrast with a previous report (Brecht et al., 1997), they indicate that rats can solve tactile object detection and discrimination tasks (a) using only the large, motile mystacial vibrissae (macrovibrissae) and (b) without engaging in head movements.We conclude that the functional contribution of the macrovibrissae will vary with the nature of the task and the conditions of testing.

Perirhinal cortex and place-object conditional learning in the rat.

The present study examined whether excitotoxic lesions of the perirhinal cortex can affect acquisition of a place-object conditional task in which object and spatial information must be integrated. Testing was carried out in a double Y-maze apparatus, in which rats learned a conditional rule of the type, "In Place X, choose Object A, not Object B (A+ vs. B-); in Place Y, choose Object B, not Object A (A- vs. B+)." Perirhinal cortex lesions significantly impaired acquisition of this task while sparing performance of an allocentric spatial memory task performed in a radial arm maze. Perirhinal cortex lesions also had no apparent effect on a 1-pair object discrimination task performed in the double Y maze or on retention and acquisition of 4-pair concurrent discrimination problems performed in a computer-automated touch screen testing apparatus. The results suggest that, although the perirhinal cortex and hippocampus can be functionally dissociated, their normal mode of operation includes the integration of object and spatial information.

Perirhinal cortex and place–object conditional learning in the rat.

The present study examined whether excitotoxic lesions of the perirhinal cortex can affect acquisition of a place–object conditional task in which object and spatial information must be integrated. Testing was carried-out in a double Y-maze apparatus, in which rats learned a conditional rule of the type, In Place X, choose Object A, not Object B (A+ vs B–); in Place Y, choose Object B, not Object A (A– vs B+). Perirhinal cortex lesions significantly impaired acquisition of this task while sparing performance of an allocentric spatial memory task performed in a radial arm maze. Perirhinal cortex lesions also had no apparent effect on a 1-pair object discrimination task performed in the double Y-maze or on retention and acquisition of 4-pair concurrent discrimination problems performed in a computer-automated touch screen testing apparatus. The results suggest that, although the perirhinal cortex and hippocampus can be functionally dissociated, their normal mode of operation includes the integration of object and spatial information.

Visual discrimination learning impairments produced by combined transections of the anterior temporal stem, amygdala and fornix in marmoset monkeys

Marmoset monkeys (Callithrix jacchus) with bilateral transections of the anterior temporal stem, amygdala and fornix were unable to relearn a 2-choice object discrimination first learnt prior to surgery, and were very severely impaired at relearning a concurrent object discrimination task which they had learnt and relearnt prior to surgery, indicating that they had a dense retrograde amnesia. They also had difficulty learning new visual object discriminations but were only mildly impaired on spatial learning. When tested on new learning of concurrent discriminations 8 to 10 weeks after surgery, three operated monkeys were unable to reach criterion in 400 trials while the remaining two operated monkeys performed within the normal range. The operated monkeys were subsequently shown to be impaired on acquisition of shape discriminations using black objects. These anterograde effects suggest that the impairment runs mainly in the domain of visual analysis. The monkeys also exhibited many of the features of the Klüver–Bucy syndrome. Histological analysis indicated that in addition to cutting some of the subcortical temporal lobe efferent pathways, the surgical procedures had cut the cholinergic afferents to the temporal neocortex, entorhinal cortex, and hippocampus. In a second experiment we found that treatment with the cholinergic agonist pilocarpine, which is effective in monkeys with specific cholinergic lesions, was unable to remediate the lesion-induced impairments. This suggests that transection of the non-cholinergic afferents, or the temporal lobe subcortical efferents, contributed to the behavioural syndrome and the learning and retention deficits seen in these monkeys.

Effects of microwave and mobile-telephone exposure on memory processes

Three behavioral tests are described using rats to examine changes associated with learning and memory tasks, following microwave exposure. Working or short-term memory was measured via object discrimination, spatial memory was assessed using a radial-arm maze with food rewards, and spatial-reference learning and memory were measured using a circular water maze. The results indicate significant SAR-dependent decreases in object discrimination, significant variation with a spatial-learning and working-memory task in the radial-arm maze for two species of animals, and significant microwave-related impairments in spatial reference memory in a circular water maze at 1.2 W/kg. Deficits in the object-discrimination task were seen at 1 W/kg but not at 0.1 W/kg, both with no measurable microwave hyperthermia. Likewise, the behavioral measures of spatial memory also indicate a SAR-related response: no impairment at 0.05 W/kg but impairment at 0.6 W/kg.

Contrasting Effects on Discrimination Learning after Hippocampal Lesions and Conjoint Hippocampal–Caudate Lesions in Monkeys

Eighteen monkeys with lesions of the hippocampal region (the hippocampus proper, the dentate gyrus, and the subiculum) made by an ischemic procedure, radio frequency, or ibotenic acid were tested on a simple, two-choice object discrimination learning task that has been shown to be sensitive to large lesions of the medial temporal lobe. The monkeys were also tested on two other discrimination tasks (pattern discrimination and eight-pair concurrent discrimination) that can be learned normally by monkeys with large medial temporal lobe lesions. All of the lesion groups were impaired at learning the simple object discrimination task. Seven of the monkeys who had sustained damage to the hippocampal region also sustained damage to the tail of the caudate nucleus. These seven monkeys, but not the other 11 monkeys with hippocampal lesions, were impaired on pattern discrimination and concurrent discrimination learning. The results suggest that the hippocampal region is important for learning easy, two-choice discriminations, whereas the caudate nucleus is necessary for the normal learning of more difficult, gradually acquired discrimination tasks. The findings support the distinction between declarative memory, which depends on the hippocampus and related medial temporal lobe structures, and habit learning, which depends on the caudate nucleus.

The Dopamine D 3/D 2 Receptor Agonist 7-OH-DPAT Induces Cognitive Impairment in the Marmoset

Previous work has shown that dopaminergic systems are involved in cognitive function in the common marmoset. The present study investigated the role of dopamine D 3 receptors in cognitive performance in the marmoset. The effects of the putative dopamine D 3 receptor agonist, 7-OH-DPAT, on performance of a same-day reversal visual object discrimination task were assessed using a miniature Wisconsin General Test Apparatus (WGTA). Within the same test session marmosets acquired a two-choice object discrimination initial task and a reversal task to criterion. 7-OH-DPAT (6–10 μg/kg) significantly impaired reversal task performance only, without affecting acquisition of the initial task. A higher dose of 25 μg/kg 7-OH-DPAT impaired initial task acquisition as well as reversal task acquisition, possibly as a consequence of a nonspecific influence on motor function. The dopamine D 2 receptor antagonist (−)sulpiride (5–10 μg/kg) and the α 2-receptor antagonist yohimbine (50 μg/kg) failed to attenuate the effects of 7-OH-DPAT (6 μg/kg) in this task. In contrast, the dopamine D 2/D 3 receptor antagonist raclopride (50 μg/kg) significantly attenuated the 7-OH-DPAT–induced impairment of reversal task performance. These results suggest that activation of dopamine D 3 receptors produces a selective impairment of aspects of cognitive function in the marmoset.