Baited Arms Research Articles

Spatial pattern learning in the radial arm maze

Rats experienced a spatial pattern of baited and unbaited arms in an eight-arm radial maze. The spatial pattern remained constant over trials, but the spatial locations that were baited varied unpredictably. Although there was no evidence of control by the spatial pattern during free choice training trials, the rats' ability to locate baited arms in forced choice test trials was superior to that of animals in a control condition for which maze arms were not baited in a consistent spatial pattern. This is consistent with the results of experiments showing that spatial choices by rats in a pole box maze are controlled by abstract spatial patterns.

Performance on spatial working memory tasks after dorsal or ventral hippocampal lesions and adjacent damage to the subiculum.

Rats with excitotoxic lesions of the dorsal or ventral hippocampus and control rats were trained on 2 spatial working memory tasks: the standard version of the radial maze with 8 baited arms and the non-matching-to-place procedure in the T maze. Dorsal lesions produced deficits in both tasks, whereas ventral lesions did not affect learning in either of them. A volumetric analysis of subicular damage showed that dorsal hippocampal lesions caused a deficit in the non-matching-to-place only when accompanied by damage to the dorsal subiculum; on the other hand, lesions to the dorsal hippocampus impaired performance in the radial-arm maze regardless of the extent of subicular damage.

Adaptive changes in a radial maze task: Efficient selection of baited arms with reduced foraging in senescent hooded rats

Qualitative differences in strategy selection during foraging in a partially baited maze were assessed in young and old rats. The baited and non-baited arms were at a fixed position in space and marked by a specific olfactory cue. The senescent rats did more re-entries during the first four-trial block but were more rapid than the young rats in selecting the reinforced arms during the first visits. Dissociation between the olfactory spatial cue reference by rotating the maze revealed that only few old subjects relied on olfactory cues to select the baited arms and the remainder relied mainly on the visuo-spatial cues.

Discrimination of what, when, and where: Implications for episodic-like memory in rats

We investigated the discrimination of what, when, and where in rats ( n = 5) using an eight-arm radial maze. Rats received daily training consisting of forced-choice visits to four baited arms, one of which was randomly chosen each day to contain chocolate (Phase 1). In Phase 2, all eight arms were available. After a short (30 min) retention interval (RI), the four arms that were not available in Phase 1 provided food. After a long (4 h) RI, the four remaining arms plus the arm containing chocolate provided food (i.e., the chocolate arm replenished). The rats visited the chocolate location after the long RI more than after the short RI. Next, chocolate was paired with lithium chloride, and subsequent testing used the long RI. The rats visited the chocolate location less after the taste-aversion manipulation than in previous training, demonstrating knowledge of what, when, and where. Implications for episodic-like memory are discussed.

Spatial configuration and list learning of proximally cued arms by rats in the enclosed four-arm radial maze.

In an enclosed four-arm radial maze, after sampling three experimenter-selected baited arms (the study segment) and following rotation of the maze, rats had to find the fourth baited arm among all four unblocked arms (test segment). The rats learned this task with two sets of arm cues, objects at arms' entrances and full arm inserts, each maintained in a fixed configuration. When we changed the configuration of one set of arms to its mirror image and that of the other set to a more mixed variation by switching opposite and adjacent cued arms, the rats' accuracy was similarly disrupted (Experiment 1). In Experiment 2, the same rats rapidly recovered their high search accuracy on four new configurations recombined from pairs of adjacent arms and pairs of opposite cued arms from t he previous finaltwo configurations. Their test segment search accuracy, however, was again disrupted when these configurations were varied either only over trials' study segments or only over trials' test segments. In Experiment 3, however, these rats attained accuracy as high on two sets of cued arms with constantly changing configurations as on two sets with constant configurations. Thus, the rats were able to separately represent four different spatially stable configurations, and then they could learn to represent two of these configurations as lists of spatially irrelevant items. We discuss these findings in terms of association theory and parallel map theory (Jacobs & Schenk, 2003).

Intraseptal tacrine-induced disruptions of spatial memory performance

The medial septal nucleus regulates the physiology and emergent functions (e.g., memory formation) of the hippocampal formation. This nucleus is particularly rich in cholinergic receptors and is a putative target for the development of cholinomimetic cognitive enhancing drugs. Several studies have examined the direct effects of intraseptal cholinomimetic treatments and the results have been somewhat conflicting with both promnestic and amnestic effects. Several variables (e.g., age, task difficulty, timing of drug administration) may influence treatment outcome. The present study examined the effects of intraseptal infusion of the acetylcholinesterase inhibitor tacrine (0–25 μg/0.5 μl) on spatial memory performance. Tacrine was infused into the medial septum just prior to testing. Tacrine infusions did not significantly affect the number of correct choices in the first eight entries, or the number of correct choices until an error. This treatment did not alter the angle of arm entries, or impair the animals’ ability to complete the task (enter all baited arms). However, tacrine produced a linear dose-dependent increase in errors, doubling (12.5 μg) and tripling (25.0 μg) the number of errors made before rats completed the task. The deficit demonstrates that activation of intraseptal cholinergic receptors can disrupt spatial memory performance. These findings are discussed with regards to septohippocampal-dependent memory processes and the development of therapeutic strategies in the treatment of age-related memory disorders.

Spatial navigation on the radial maze with trial-unique intramaze cues and restricted extramaze cues.

We investigated the use of extramaze and intramaze cues on the eight-arm radial maze. The rats received daily training consisting of forced-choice visits to four baited arms, a retention interval, and the availability of all eight arms with baits available at arms that did not appear in the forced-choice phase. The radial maze was placed in a featureless octagonal enclosure to minimize the availability of extramaze cues. Intramaze cues were provided at the distal end of each arm by placing a small object in front of the food trough; unique objects were randomly sampled from a large pool of objects. The use of extramaze and intramaze cues was assessed by rotating the objects, after the retention interval, on occasional non-rewarded probes, thereby dissociating the location of extramaze and intramaze cues. The rats used extramaze rather than intramaze cues. Implications for spatial representations are discussed.

Reward modulates neuronal activity in the hippocampus of the rat

In the hippocampus of freely moving rats, neurons have been recorded that fire predominately when the animal travels through a particular area while exploring the environment (so-called ‘place cells’). This study investigates if the neuronal firing characteristics of such cells are modulated by attention, expectation of reward or memory load. A total of 16 electrodes were implanted in the CA1 region of the hippocampus of 3-month-old Long–Evans rats. Using a tetrode recording system, single neurons were recorded while a rat explored an 8-arm maze and retrieved pellets at the end of each arm. It was found that 31 out of 67 neurons showed place cell characteristics, while the other cells either fired in more than one place or fired along whole arms of the maze. Interestingly, 11 of the 31 neurons showed enhanced firing activity when the animal entered a baited arm but did not fire when the arm was visited again after the bait had been retrieved. In a second experiment, only four out of eight arms were baited. Firing rates of 46 neurons were analysed, and all cells (spatial or non-spatial) fired more in baited arms than in non-baited ones ( P<0.001). In a reversal task in which the previously unbaited four arms were subsequently baited, neuronal activity was increased in the newly baited arms (42 cells analysed, P<0.001). Since no alterations to the maze or cues have been made, we interpret the increased firing probability of neurons in baited arms compared to unbaited arms as a correlate for ‘attention’ or ‘expectation’.

Rats form cognitive maps from spatial configurations of proximal arm cues in an enclosed 4-arm radial maze

Rats were trained to select a final, remaining baited arm following a 6- to 10-min delay following their entries into three experimenter-selected baited arms in an enclosed 4-arm radial maze containing different proximally cued arms. Rats’ accuracy in selecting the remaining baited arm was disrupted when the spatial configuration of arm cues was randomly varied over trials following initial training with one configuration in Experiment 1. In Experiment 2, the same rats acquired this task with the original and a new configuration of the same arm cues when each consistently occurred at a specific time of day (one in the morning, the other in the afternoon). Randomly varying the temporal presentations of these configurations following acquisition disrupted rats’ choice accuracy more within the new than the original configuration. Other rats in Experiment 3 learned this task with two configurations containing different types of arm cues (full arm inserts, objects at the arm entrances). When required to relearn this task with recombined configurations of pairs of arm cues from of each configuration, only rats presented pairs of arms arranged differently from that in their original configurations were unable to reacquire the task. Together these results support a cognitive map hypothesis more than a proximal arm cue list hypothesis. These findings were discussed in terms of recent versions of cognitive map theory ( Benhamou, 1998; Poucet, 1993) and the possible limits of such processing ( Roberts, 2001).

Spatial Working Memory and the Brainstem Cholinergic Innervation to the Anterior Thalamus

The anteroventral thalamic nucleus (AV) has a role in spatial memory, but the influence of the prominent brainstem cholinergic projection to this region is unknown. Here, spatial memory in a 12-arm radial maze was examined after 0.15 microl bilateral AV infusions of scopolamine. In part one, rats visited six arms singly (the phase 1 arms) and, after a 10 min delay, were allowed free choice to both phase 1 arms and the remaining six baited arms (phase 2 arms). Scopolamine (10 microg) administered during the delay increased errors to both phase 1 and phase 2 arms, whereas PBS infusions increased phase 1 arm errors only. The PBS effect was the result of inserting the internal cannulas alone and not the infusion. The same dose of scopolamine (10 microg) infused before maze testing (part two: no phase 1 arms, no delay) also impaired spatial memory over and above the effects of both PBS and no-infusion, which did not differ markedly. Part two also showed that choice latency and choice strategies were unaffected by PBS and scopolamine. Cannulation and infusion procedures in both parts one and two did not produce any negative carryover effects across multiple control (no internal cannula) sessions, and a trypan blue manipulation indicated that infusions were restricted to the AV region. This study provides the first direct evidence that the brainstem cholinergic innervation to the limbic thalamus influences learning and memory, which may have important implications for human neurological conditions such as alcohol-related disorders and schizophrenia.

Nimodipine prevents the effects of ethanol in tests of memory

The effects of acute administration of the dihydropyridine calcium channel antagonist, nimodipine, were studied on the actions of ethanol in the radial arm maze and the object recognition test. In the former test, the effects of the drugs were examined on the performance in finding the four baited arms, after previous training in this task. Ethanol, at 1 g/kg, increased both the number of re-entries into baited arms (counted as errors of working memory) and the total number of arm choices required to complete the task. Administration of nimodipine, 10 mg/kg, with the ethanol, completely prevented the deleterious effects on memory in this task, but had no effects on the performance when given in the absence of ethanol. In the object recognition task, ethanol, 1 g/kg, significantly decreased the differences in the time spent exploring novel and familiar objects. Nimodipine, 10 mg/kg, given with the ethanol, completely prevented this effect, but nimodipine alone had no effects. The lack of changes in total exploration times indicated that the effects of ethanol in these tests were not due to loss of motor co-ordination or of alertness. The results are discussed in the light of the known actions of the drugs on brain function.

Impaired metabolic capacity in the perirhinal and posterior parietal cortex lead to dissociation between attentional, motivational and spatial components of exploration in the Naples High-Excitability rat

This study aimed at investigating the neural substrates of spatial and non-spatial Behavioural components of exploration to novelty by a neurogenetic approach. Thus, functional imaging and Behavioural analysis were carried out in the Naples High-Excitability (NHE) rats, a model of hyperactivity and attention-deficit. Quantitative cytochrome oxidase (C.O.) histochemistry was used to measure the basal metabolic capacity of different forebrain structures. In parallel experiments, exploration in an 8-arm radial maze (Olton-maze) with extra-maze cues was used to measure attentional, motivational and spatial components of Behaviour after feeding rats’ ad-libitum or at a reduced diet. Functional imaging analysis: brains from naive rats were stained for quantitative C.O. histochemistry along with standards. NHE rats showed lower C.O. activity in perirhinal and posterior-parietal cortex (all layers) and cortical amygdala, and greater activity in entorhinal cortex (superficial layers). The outer granular cell layer of the dentate gyrus had greater activity in NHE. Behavioural analysis: at low and high motivational level, maze exploration was reinforced during shaping throughout and then only a single arm. The Behaviour was monitored by a CCD camera and videotaped. (i) There was no line difference in working memory during non reinforced maze exploration, independent of the motivational level; (ii) during shaping with all baited arms, there was no line difference in working memory, but NHE rats showed a very low or lower food consumption at low and high motivational level, respectively; (iii) rats showed a higher working memory in finding the single baited arm at high motivational level; (iv) NHE rats paid little attention towards reinforcement upon visiting the baited arm only at low motivational level. Thus, Behavioural and functional neuroimaging analysis suggests the neural substrates of spatial and non-spatial components of exploration to be underlined by different network operations in the neocortical and limbic cortices in the NHE rat lines. Therefore, they appear as an useful tool to the understanding of Attention-Deficit Hyperactivity Disorder (ADHD) in children. (Supported by Telethon–Italy grant E.513).

Spatial working memory improvement by an α 2-adrenoceptor agonist dexmedetomidine is not mediated through α 2C-adrenoceptor

1. Aged α 2C-adrenoceptor knockout and wild type mice were used to investigate whether α 2C-adrenoceptors are involved in mediating the beneficial effects of α 2-adrenoceptor agonist, dexmedetomidine, on spatial working memory. 2. A win-stay task in the radial arm maze was used to dissociate the effects of dexmedetomidine on working vs. reference memory. In addition, the animals were tested in simple response habit learning in the T-maze. 3. Knockout mice made more working memory errors after the change of the baited arm in radial arm maze, but after training reached again as accurate level of performance as wild type controls. Dexmedetomidine 5 and 10 μg/kg alleviated the increase in spatial working memory errors after the change of the baited arm in knockout mice. Knockout and wild type mice performed equally well in T-maze, and dexmedetomidine had no effect on this simple response learning. 4. The present results indicate that α 2-adrenoceptor agonists have a selective effect on spatial working memory not only in monkeys but also in mice. Further, this study confirms our earlier finding that the presence of α 2C-adrenoceptors is not necessary for the spatial working memory enhancing effect of α 2-adrenoceptor agonists.

Use of Win-Stay and Win-Shift Strategies in Place and Cue Tasks by Medial Caudate Putamen (MCPu) Lesioned Rats

This study investigated the behavioral function of the medial caudate putamen (MCPu) in the solving of maze tasks. MCPu lesioned rats (n = 35) and control rats (n = 35) were trained for the place or cue task (the four baited arms and four unbaited arms task) in an eight-arm radial maze, which requires the win-stay or the win-shift strategy. In Experiment 1, in which the place task was used, MCPu lesioned rats could learn the task in the win-shift condition, but not in the win-stay condition. MCPu lesioned rats made a lot of unbaited errors in the win-stay condition, as they persistently chose adjacent arms. Control rats could learn the tasks in both conditions. In Experiment 2, in which the cue task was used, MCPu lesioned rats and control rats could learn the tasks in both the win-stay and the win-shift conditions. If anything, the performance of MCPu rats was a little better than that of control rats in the win-stay condition. The results of these two experiments revealed that the MCPu was involved in solving the win-stay place task, but not the win-shift place, win-stay cue, and win-shift cue tasks. These findings suggest that the MCPu plays an important role in utilizing both spatial information and switching foraging strategies flexibly and efficiently, that is, processing complicated visuospatial cognition.

A 5-arm maze enables parallel measures of sustained visuo-spatial attention and spatial working memory in mice

A 5-arm maze has been developed to provide parallel tests of sustained visuo-spatial attention and spatial working memory in mice. C57Bl/6 mice were trained to select, either by immediate response (attention) or by delayed-matching response (working memory), one target arm among the five open arms. For attention testing, mice were first trained to acquire the basic task in which one randomly selected baited arm remained lit until a choice was made. Criterion of >80% correct with a response latency <5 s was attained in 52–56 trials. Following this, attention was tested by using trials wherein light signal durations of 2, 1 or 0.5 s were intermixed to vary attentional load. In the working memory test, mice were submitted to a forced visit to a randomly selected baited arm during a presentation phase. Following a variable retention interval (R.I.), mice were replaced into the maze and rewarded for choosing this arm. Criterion of >80% correct was attained in 35–40 trials and mice exhibited high levels of retention for R.I.s up to 4 h. Results validate the 5-arm maze for evaluation of both sustained visuo-spatial attention and spatial working memory in mice. Both the tasks are rapidly acquired and the 20% chance level provides high resolution for evaluating performance. This comparative strategy allows to dissociate attention and memory and to reveal deficits in these processes during ageing or in knockout strains. The high level of retention performance over R.I.s of 4 h enables studies using pharmacological treatments differentially affecting the acquisition, encoding, retention or retrieval phases of working memory. Furthermore, functional brain imaging studies may be used to identify neuronal networks which are differentially activated during these distinct phases.

Gestational-lactational exposure to Aroclor 1254 impairs radial-arm maze performance in male rats.

Developmental exposure to polychlorinated biphenyls (PCBs) has been associated with cognitive deficits in children. The current study assessed effects of gestational and lactational exposure to a commercial PCB mixture, Aroclor 1254 (A1254), on spatial learning and memory in rats, using the radial-arm maze (RAM). Pregnant Long-Evans females (10/dose group) were exposed to 0 or 6-mg/kg/day A1254 (po in corn oil) from gestation day (GD) 6 to weaning at postnatal day (PND) 21. After they reached adulthood, 1 male and 1 female from each litter were tested on a working/reference memory task using a 12-arm RAM. Eight of the 12 arms were baited, with the pattern of baited arms remaining the same on every trial for each rat. Compared to control males, the A1254-exposed males made significantly more working memory errors (2.15 +/- 0.13 and 3.20 +/- 0.18 errors +/- SEM for control and A1254 males, respectively) and reference memory errors (3.17 +/- 0.10 and 4.13+/-0.14 errors +/- SEM for control and A1254 males, respectively) on the RAM. In contrast, A1254-exposed females were not impaired relative to control females on the RAM. Drug challenges with dizocilpine (MK-801) and scopolamine did not differentially affect working or reference memory of control and exposed rats. These data suggest that perinatal exposure to A1254 may cause sex-specific deficits in spatial learning and memory, and that NMDA-mediated and muscarinic neurotransmission, as assessed with the drug challenges, were not markedly impaired in the A1254-exposed animals.

Rule-Based Learning Impairment in Rats with Lesions to the Dorsal Striatum

The present study examined the effects of lesions to the dorsal striatum (DS) in Sprague-Dawley rats, when tested on the acquisition and successive shifts in the position of a goal arm in an eight-arm radial maze. In the procedure we used, rats had to retrieve the location of one baited arm among the eight arms of the maze after it had just been presented as a sample during a forced trial. After attainment of a fixed learning criterion, rats were submitted to five successive shifts in the goal location. Results showed that DS rats were able to learn the position of the goal arm during the acquisition phase as efficiently as sham-operated rats. In contrast, when the position of the goal arm was shifted, although DS rats were able to learn its new position, they made significantly more errors and required more sessions to reach criterion than sham-operated rats. These results suggested that both groups did not solve the task using the same behavioral strategy. The analysis of responses made suggested that sham-operated rats solved the task using the pairing rule between the forced and the free run (matching-to-sample rule), while DS rats solved the task using only visuo-spatial processing. These data therefore suggest that the dorsal striatum plays an important role in rule-learning ability.

Consolidation of Memory After its Reactivation: Involvement of ß Noradrenergic Receptors in the Late Phase

Evidence is growing that the cAMP pathway through the cAMP responsive element binding protein (CREB) transcription factor plays an important role in long-term memory formation (LTM). To study the role of β-noradrenergic receptors, positively linked to the cAMP secondmessenger system, in the dynamics of LTM processes, we used a memory-reactivation paradigm because recent studies in our laboratory confirmed that reactivated memory is labile and undergoes an extended reconsolidation process. In an eight-arm maze, rats were trained to choose the same three baited arms; 24 hr later, memory was reactivated and then the rats were injected intracerebroventricularly at 5 min, 30 min, 60 min, or 5 hr later with the β-antagonist timolol or with saline. The results showed that injection of timolol induced amnesia only at the 60 min post-reactivation interval, whereas all control groups and groups that were timolol-injected at other post-reactivation intervals displayed optimal retention. The delayed amnesic action of timoloi suggests that β noradrenergic receptors and the cAMP cascade are implicated in the late phase of reprocessing of a remembered event.

Effects of electrolytic lesions of the medial prefrontal cortex or its subfields on 4-arm baited, 8-arm radial maze, two-way active avoidance and conditioned fear tasks in the rat

The present study tested the effects of electrolytic lesions in two mPFC subregions, the dorsal anterior cingulate area (dACA) and prelimbic cortex, as well as the effects of a larger medial prefrontal cortex (mPFC) lesion which included both subregions, on 4-arm baited, 4-arm unbaited, 8-arm radial maze task and its reversal (Experiments 1 and 4), two-way active avoidance (Experiments 2 and 5) and conditioned emotional response (Experiments 3 and 6). Rats with large or small lesions of the mPFC learned the location of the 4 baited arms in the training and reversal stages of the radial maze task similarly to sham rats, indicating that these lesions did not affect animals' capacity to process and remember spatial information. dACA and mPFC lesions produced a transient deficit in the acquisition of the radial maze task, suggestive of an involvement of these regions in mnemonic processes. However, in view of the normal performance of these groups by the end of training and during reversal, this deficit is better interpreted as stemming from a difficulty to learn the memory-based strategy used to solve the task. Only mPFC lesion led to better avoidance performance at the beginning of training and tended to increase response during the presentation of a stimulus previously paired with shock, compared to sham rats. Both effects can be taken as an indication of reduced emotionality following mPFC lesion. The results are discussed in relation to known behavioral functions of the mPFC and the suggested functional specialization within this region.

Both anteromedial and anteroventral thalamic lesions impair radial-maze learning in rats.

Disruption to the anterior thalamus (AT) may be an important factor in diencephalic amnesia. Rats with small lesions of the anteromedial (AM) or anteroventral (AV) nucleus showed persistent working-memory and reference-memory deficits in a 12-arm radial maze, although they were comparable to controls during the early part of training. The only activity difference in the maze was that lesioned rats failed to run more slowly when revisiting a baited arm. For all groups, both working and reference memory were impaired after extramaze cues were removed; removal of intramaze cues further impaired performance relative to the original conditions. These findings suggest the AT makes a distinct contribution to mnemonic functions, probably as part of an integrated system involving limbic cortex and the hippocampal formation, and that AT lesions produce a general rather than a specific deficit in spatial or working memory.