Goal Arm Research Articles

Appetitive position discrimination in the T-maze

This protocol details a method to perform appetitively motivated tasks in rodents to test cognitive ability. When testing cognition in animals, the simplest paradigms can potentially yield quick results with minimal investment from the experimenter. Although appetitively motivated tasks are generally learnt more slowly than aversively motivated ones, they may be essential for distinguishing the effects of a treatment on learning from its effects on aversive motivation per se. For example, if a treatment improves learning in both types of paradigm, this is better evidence that it affects cognition rather than sensorimotor processes. Rats and mice easily learn position discriminations in a T-maze, especially if multiple cues, such as different objects and floor textures in the goal arms, are provided. To start, the rodent is placed in the maze and it chooses an arm. This Trial 1, however, is the only one on which this arm will be rewarded. From now on, it must always choose the other arm. The rule is simple: for example, always turn left into the arm with diagonal black stripes on the walls and gravel glued to the floor. High levels of correct responding can be achieved within 20-40 trials. The test may therefore be particularly useful with animals of low cognitive ability, such as transgenic mice derived from some 129 or SJL strains. Once the animals are habituated, each trial should take approximately 1 min. Thus, to test ten animals for 40 trials would take around 7 h.

T-maze alternation in the rodent

This protocol details a method for using a T-maze to assess the cognitive ability of rodents. The T-maze is an elevated or enclosed apparatus in the form of a T placed horizontally. Animals are started from the base of the T and allowed to choose one of the goal arms abutting the other end of the stem. If two trials are given in quick succession, on the second trial the rodent tends to choose the arm not visited before, reflecting memory of the first choice. This is called 'spontaneous alternation'. This tendency can be reinforced by making the animal hungry and rewarding it with a preferred food if it alternates. Both spontaneous and rewarded alternation are very sensitive to dysfunction of the hippocampus, but other brain structures are also involved. Each trial should be completed in under 2 min, but the total number of trials required will vary according to statistical and scientific requirements.

Impaired Outcome-Specific Devaluation of Instrumental Responding in Mice with a Targeted Deletion of the AMPA Receptor Glutamate Receptor 1 Subunit

The present study evaluated the proposal that mice with a targeted deletion of the glutamate receptor 1 (GluR1) subunit of the AMPA receptor are impaired in using an instrumental or pavlovian signal to gain access to a representation of the sensory-specific motivational properties of a primary reward. In experiment 1, mice were trained to approach two goal boxes in a plus-maze; each goal box contained a different reward (sucrose solution vs food pellet). After acquisition, one of the rewards was devalued by an outcome-specific satiety procedure. Subsequent test trials performed in extinction showed an increase in the latency to enter the devalued goal arm, relative to the nondevalued goal arm in control but not GluR1-/- mice. In experiment 2, a similar outcome-specific satiety procedure was used to examine the effects of reward devaluation on an instrumental nose-poke response. During testing, control but not GluR1-/- mice decreased their rate of responding on a nose poke associated with a devalued reward. A subsequent choice test showed that GluR1-/- mice were able to discriminate between the devalued and nondevalued outcomes used in both experiments. These deficits mirror those seen after lesions of the basolateral amygdala and suggests that GluR1-mediated neurotransmission in this region contributes to encoding the relationship between sensory-specific aspects of reward and their incentive value.

The role of hippocampal glutamate receptor-A-dependent synaptic plasticity in conditional learning: the importance of spatiotemporal discontiguity.

Gene-targeted mice lacking the AMPA receptor subunit glutamate receptor-A (GluR-A or GluR1) and mice with cytotoxic hippocampal lesions were compared with wild-type and sham-operated controls, respectively, on a conditional learning task using an elevated T-maze. Floor inserts (white perspex vs wire mesh) provided a conditional cue indicating in which goal arm a food reward was to be found. The relationship between the floor insert and the rewarded goal arm was constant throughout the experiment. Both lesioned and knock-out mice were able to acquire the task if the floor inserts extended throughout the entire maze, including the start arm and both goal arms. In contrast, both lesioned and knock-out mice were unable to acquire the task if the floor inserts were only present in the start arm of the maze. The absence of the conditional cue (the floor insert) at the time when the place-reward association was experienced thus critically determined whether or not the mice were impaired. We suggest that hippocampal GluR-A-dependent synaptic plasticity contributes to a memory system in rodents for encoding both the spatial and temporal contexts (the where and the when) associated with a particular event.

Amygdala and “emotional” modulation of the relative use of multiple memory systems

The basolateral amygdala modulates the cognitive and habit memory processes mediated by the hippocampus and caudate nucleus, respectively. The present experiments used a plus-maze task that can be acquired using either hippocampus-dependent “place” learning or caudate-dependent “response” learning to examine whether peripheral or intra-basolateral amygdala injection of anxiogenic drugs would bias rats towards the use of a particular memory system. In Experiment 1, adult male Long–Evans rats were trained to swim from the same start point to an escape platform located in a consistent goal arm, and received pre-training peripheral injections of the α 2-adrenoceptor antagonists yohimbine (2.5 or 5.0 mg/kg), RS 79948-197 (0.05, 0.1, or 0.2 mg/kg), or vehicle. On a drug-free probe trial from a novel start point administered 24 h following acquisition, vehicle treated rats predominantly displayed hippocampus-dependent place learning, whereas rats previously treated with yohimbine (2.5, 5.0 mg/kg) or RS 79948-197 (0.1 mg/kg) predominantly displayed caudate-dependent response learning. In Experiment 2, rats receiving pre-training intra-basolateral amygdala infusions of RS 79948-197 (0.1 μg/0.5 μl) also predominantly displayed response learning on a drug-free probe trial. The findings indicate (1) peripheral injections of anxiogenic drugs can influence the relative use of multiple memory systems in a manner that favors caudate-dependent habit learning over hippocampus-dependent cognitive learning, and (2) intra-basolateral amygdala infusion of anxiogenic drugs is sufficient to produce this modulatory influence of emotional state on the use of multiple memory systems.

High level estradiol impairs and low level estradiol facilitates non-spatial working memory

The present study investigated the effect of different doses of estradiol treatment on performance in the non-spatial delayed alternation T-maze a task in which performance is mediated by the integrity of the prefrontal cortex (PFC). Ovariectomized (OVX) female rats were injected with estradiol benzoate (0.3 μg/0.1 ml sesame oil (EB0.3), 5 μg/0.1 ml sesame oil (EB5) or 10 μg/0.1 ml sesame oil (EB10)) or vehicle (sesame oil, 0.1 ml). Approximately 2 h after each injection, animals were trained daily on the T-maze with an initial delay of 10 s (short delay). Following a month with no treatment animals were re-trained at a 40 s delay (long delay). Days to reach criterion (one error per day for three consecutive days), mean total errors, errors across days, change in performance across training (short subtracted from long delay), and latency to reach goal arm, were scored. At the short delay, there was a weak effect for the low dose of estradiol (EB0.3 low-to-medium physiological) to significantly decrease the number of working memory errors compared to controls. However at the longer delay the higher doses of estradiol EB5 (high physiological) and to a lesser extent EB10 (suupraphysiological) significantly increased the number of working memory errors compared to controls. These data demonstrate the differential effect of estradiol during short and long delays on prefrontal cortex dependent working memory. High levels of estradiol impair PFC-dependent working memory at longer delays, while low level estradiol weakly facilitates PFC-dependent working memory at a shorter delay. These data suggest that estradiol’s facilitatory effects on working memory may not be mediated through the PFC, while estradiols inhibitory effects on working memory may be mediated at least in part through the PFC.

Intramaze and Extramaze Cue Processing in Adult APPSWE Tg2576 Transgenic Mice.

The present study examined spatial and nonspatial learning in adult Tg2576 mice. Transgenic mice were impaired in acquisition of a T-maze forced-choice alternation task. However, mutant mice were as sensitive as control mice to the introduction of retention intervals and proactive interference, and this suggested that short-term memory processes were intact in Tg2576 mice. Probe trials revealed that the Tg2576 mice did not use an allocentric strategy to navigate to the goal arm. However, mutant mice acquired an intramaze brightness discrimination, a simple room discrimination, and a contextual biconditional left-right discrimination in a T maze. Results suggest that Tg2576 mice are able to process both intramaze and extramaze stimuli but are impaired in forming an allocentric representation of their environment.

Effect of age on the radial arm water maze—a test of spatial learning and memory

Aged rats show decrements in performance on cognitive tasks that require the use of spatial learning and memory. We used the 8-arm radial water maze (RAWM) to measure spatial learning as a function of age in young (6 months) and old (21 months) male F344 rats. Rats were placed in the RAWM in different start arms with the same goal arm for 3 days (five trials/day); the goal arm was changed on day 4. Old rats demonstrated spatial impairment as evidenced by increased latencies to find the hidden platform on day 4. Old rats made significantly more errors, both reference and working memory errors, than young rats on all days. It is likely that the old rats utilized non-spatial strategies to solve the task, and therefore were impaired in learning a new platform location. The RAWM is a reliable, sensitive, and powerful additional test to assess age-related spatial learning and memory deficits, combining the advantages of the Morris water maze and the radial arm maze while minimizing the disadvantages.

Hippocampal damage in rats disrupts decrements in the processing of an intramaze landmark in a spatial task

Using a four-arm plus-shaped maze, rats with neurotoxic lesions in the dorsal hippocampus were trained in a spatial reference memory task in which both the extramaze constellation of stimuli and an intramaze landmark (a piece of sandpaper covering the floor of the goal) indicated the location of the goal arm. After reaching criterion, animals were given two transfer tests in order to investigate how much they had learned about the intra and extramaze cues. Results showed that during the intramaze transfer, based exclusively on the intramaze cue, hippocampal rats produced a performance clearly superior to that of the controls. Importantly, the average percentage of correct responses recorded in the hippocampal group during the extra versus the intramaze transfer test was similar. Thus, no decremental processing of the intramaze cue was detected in the lesioned group. In contrast, control rats showed a decremental processing of the intramaze landmark performing worse during the intramaze transfer as compared with the extramaze transfer. These results support the view that the hippocampus regulates decremental changes in the processing of normally irrelevant stimuli, extending this claim into a spatial domain.

Sex differences in the dynamics of cue utilization and exploratory behavior

The purpose of the present study was to investigate the effects of sex and estrous cycle on exploratory behavior, as well as the degree to which reliance on environmental cues changes with training. Fischer 344 rats were placed three times in an open field box that contained three objects (two identical bottles and a cylinder). During the initial exposure to the environment all females showed higher activity levels and explored a larger region of the environment compared to males. However, upon subsequent exposure to the same environment, these sex differences disappeared. During the third and final session, the locations of the bottle and the cylinder were switched. The estrous females and to a lesser degree male rats, responded to the relocation of objects with a renewal of exploration and activity; proestrous females did not show this response. The rats were then trained on a four-arm radial maze reference memory task. The correct arm could be located by its relation to extra-room cues, a large distal white panel, or to local inserts on the maze. Once the animals consistently chose the goal arm, a probe session was conducted to determine which cues the animals were using to solve the task. During the probe trial both the white panel and the local inserts were rotated 90° clockwise and counterclockwise respectively and the animals’ choice of arm recorded. During the first probe, females tended to rely on all three types of cues in solving the task. With additional training there was a shift towards predominantly using the distal visual information. In contrast, male rats did not show this shift; by the first probe session the males were predominantly using the distal visual information to solve the task. The findings indicate: (1) sex differences in the initial use of environmental cues; (2) the usage of environmental information is dynamic and changes with additional exposures to the environment. The results are related to previous findings on sex differences and estrous cycle effects, with an emphasis on the implications for hippocampal processing.

Evidence for a relationship between place-cell spatial firing and spatial memory performance.

The rat hippocampus contains place cells whose firing is location-specific. Although many properties of place cells have been uncovered, little is known about their actual contribution to the animal's spatial performance. In this study, we addressed this issue by recording place cells while rats solved a continuous spatial alternation task in which they had to alternate between the two arms of a Y-maze to get a food reward in the third (goal) arm. By manipulating the information available to the animals, we induced the cells to establish their fields in locations that were out of register relative to their standard position, thus making them inconsistent with the learned spatial task. When this happened, the rats' performance in the alternation task was markedly decreased. In addition, the nature of the behavioral errors during inconsistent field placements also changed dramatically in a way that was highly indicative of the rats' spatial disorientation. These results suggest that there is a functional relationship between the spatial firing patterns of place cells and the spatial behavior of the rat, thus strengthening the idea that these cells are part of a navigational system.

The hippocampus and flexible spatial knowledge in rats.

Lesions to the hippocampal system in rats result in a profound impairment of place or locale spatial learning although other learning strategies remain unaltered. The main objective of the present study was to investigate whether the spatial knowledge preserved in the hippocampal animals can be expressed flexibly under conditions different from those of the acquisition period. Rats with neurotoxic lesions to the dorsal hippocampus and sham-operated subjects were trained to reach the goal arm in a four-arm plus-shaped maze using a constant starting arm. During the training a transparent plexiglas barrier divided the maze in two equal halves in such a way that the animals could only travel from the starting arm to the goal arm, not having access to the remaining 50% of the maze. After seven days of training, a transfer test was used in which the starting arms were the two arms from which the animals had not started during the training phase. Results indicated that the lesioned rats made significantly more errors than the control subjects. But the most interesting results revealed that the kind of error made by the lesioned animals was congruent with the turn that they had to make during the acquisition phase in order to access the goal arm (reinforced). These results suggest that when the hippocampus is damaged a preserved highly inflexible egocentric strategy is employed to solve the spatial problem.

Progestins influence performance on cognitive tasks independent of changes in affective behavior

In this study, the effects of progestins on various cognitive and affective tasks were investigated. Ovariectomized rats (N = 72) received subcutaneously 0.0, 4.0, or 8.0 mg/kg of progesterone (P), dihydroprogesterone (DHP), or 5α-pregnan-3α-ol-20-one (3α,5α-THP) suspended in 10% ethanol/sesame oil v/v. For the cognitive tasks (Y-maze, inhibitory avoidance, and object recognition), the subjects were injected after habituation and training trials and were tested 24 h later. For the nociception and affective tasks (open field, elevated plus-maze, and tailflick), the subjects were injected 1 or 24 h before testing. P reduced latencies to the goal arm in the Y-maze, enhanced latencies to the shock-associated side of the inhibitory avoidance chamber, and increased the percentage of time with a novel object. DHP reduced latencies to the goal arm, increased the percentage of correct choices in the Y-maze, and increased crossover latencies in the inhibitory avoidance task. 3α,5α-THP administration enhanced performance in the inhibitory avoidance task. P, DHP, and 3α,5α-THP increased the number of entries into the central squares of a brightly lit open field, open arm time in the elevated plus-maze, and tailflick latencies, when administered 1 h, but not 24 h, prior to testing. These data suggest that some progestins, when administered following habituation and training and 24 h prior to testing, produce changes in cognitive performance that do not coincide with overt changes in the affective behaviors examined.

Long‐term spatial memory in rats with hippocampal lesions

In animal models of human amnesia, using lesion methods, it has been difficult to establish the role played by the hippocampus in the formation of long-term spatial knowledge. For example, lesions sustained after acquisition have generally produced a flat retrograde amnesia for spatial information. These results have not made it possible to dissociate the participation of the hippocampus in retrieval/performance processes from its participation in consolidation/retention. The present study was designed to investigate if electrolytic hippocampal lesions made before training lead to a deficit in the long-term retention of spatial knowledge when the rats show equal performance levels during the acquisition. Results show that lesioned rats learn a place response just as well as the control rats when, during the training, an intramaze cue orients the animal in its navigation towards the goal arm. One day after reaching criterion, lesioned and control rats remember the task perfectly during a transfer test in which the intramaze signal used previously is not present. However, 24 days later, the hippocampal animals manifest a profound deficit in the retention of the spatial information. When the spatial task learned during the acquisition phase requires only the use of a guidance strategy, control and lesioned animals show the same level of performance during the training phase and the same degree of retention during the retraining phase 24 days after criterion. Taken together, these results suggest that the hippocampus plays a crucial role in long-term retention of allocentric spatial information.

Influence of the shape of the experimental room on spatial learning in rats

Rats and other mammals can orient themselves in their habitat and locate various goals using different learning strategies. When a cartographic or local strategy is used, the animals construct and store in their long-term memories a complex representation of the extramaze space. However, exactly what constitutes the behaviorally key components of the extramaze space is still little known. The purpose of this study was to investigate whether the shape of the environment that surrounds the animal is an informative factor when a cartographic strategy is used. Two experiments were performed in which the rats were trained to find food in the goal arm of a four-arm, plus-shaped maze. Experiment 1 shows that lesions to the hippocampus impair the acquisition of this task, which suggests that in fact, a cartographic strategy is necessary to solve it. In Experiment 2, in which only one group of neurologically intact rats was used, we directly manipulated the shape of the space around the maze. The results showed that once the animals have learned the task, the hiding of all the extramaze single landmarks while keeping intact the general shape of the experimental room does not affect performance. Only when the shape of the surrounding space was modified did the performance deteriorate significantly. These results are discussed in relation to the different components of the extramaze environment and the contribution of each of them to the spatial learning.

Breakfast in the nook and dinner in the dining room: time-of-day discrimination in rats

Four studies were conducted which demonstrate that most (63%) male Sprague–Dawley rats can attain criterion, nine correct choices over ten consecutive trials, on a time-of-day discrimination in an elevated T-maze, but that the task is relatively difficult. The discrimination required that the rats go to one goal arm during a morning session and the other in an afternoon session. The sessions always began at the same time and were at least 6 h apart. A larger proportion of rats attained criterion and required fewer trials when the discriminative cue was a maze insert providing visual and tactile stimulation (0.72), orientation and position of the maze in the room (0.88), or the rats were required to always make the same left or right turn (0.94). Also, once criterion was attained, rats trained on time-of-day discrimination only made about 70% correct choices with continued training. Housing the rats with continuous light, all laboratory noises masked with white noise, and a random feeding schedule did not prevent them from acquiring the time–place discrimination. Testing the rats with a random number of trials during morning and afternoon sessions and with added or omitted sessions revealed that the rats did not use response or session alternation strategies to perform the discrimination. Also, the particular experimenter administering the morning or afternoon sessions did not serve as a cue for the discrimination. The relative difficulty of the task suggests that time of day does not normally function as a discriminative stimulus for choices, but probably as a contextual stimulus. Further, performance of the task in the absence of time-of-day cues suggests that the discrimination is based on event memory combined with an internal timing mechanism.

Spatial localization of a goal: Beacon homing and landmark piloting by rats on a radial maze

We performed six experiments in order to examine the ability of rats to use moving beacons and landmarks as cues to the location of reward on an eight-arm radial maze. In Experiments 1–4, the cues and goals were moved before each trial, and groups in which a single beacon was placed on the rewarded arm, a single landmark indicated that reward was on the arm immediately to the left of a landmark, or two landmarks were placed on each side of the reward arm were compared. The rats rapidly learned to track the reward in the beacon condition, failed to find the reward sooner than chance expectation with a single landmark, and did only slightly better than chance with two landmarks. In Experiments 5 and 6, the rats were trained in five trials per day, with the landmark and goal locations constant over daily rewarded trials, and in two extinction trials that were inserted among the rewarded trials. The rats found the goal arm at substantially better than chance expectancy with both one and two landmarks. Our results, in agreement with data from recent swimming pool experiments (A. D. L. Roberts & Pearce, 1998), show that rats will use the relationship between moving landmarks and a goal in order to find reward.

Behavioral strategy shifts with training: Rats on an elevated plus maze

Rats use a multitude of cues within the environment to guide their behavior. The purpose of this study was to investigate the degree to which reliance on local cues, visual extramaze cues, and other sources of information changes with training. Female Fischer 344 rats were trained consecutively for 24 days on a four-arm radial maze reference memory task. The correct arm could be located by its relation to the “outside world,” a large white illuminated poster, or to a local insert on the goal arm. Within 2 weeks, the animals were consistently choosing the goal arm regardless of how they were placed on the maze. Four and 10 days after reaching asymptotic performance, a probe trial was given to determine what strategy the animals were using to solve the task. During the probe trial, both the visual extramaze cue and the local cues were rotated 90° clockwise and counterclockwise, respectively, and the animals’ choice of arm was recorded. This probe revealed which cues had the greatest influence on each animal’s behavior. Initially, the animals tended to use all three types of cues equally in solving the task. With additional training, there was a shift toward predominantly using visual extramaze information and ignoring information outside of the testing environment. Thus, the use of environmental information is dynamic, even within a specific task, and it changes with the extent of the training.

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.

The Neurosteroids DHEA and DHEAS May Influence Cognitive Performance by Altering Affective State

The effects of Dehydroepiandrosterone (DHEA) and its sulfate ester, Dehydroepiandrosterone sulfate (DHEAS) on performance in various cognitive and affective tasks were investigated. Ovariectomized rats ( n = 48) received 0.0, 3.0, or 7.5 mg/kg s.c. of DHEA or DHEAS suspended in 10% ethanol/sesame oil v/v. For the cognitive tasks (water maze, Y-maze, passive avoidance, and object recognition), subjects were injected after training trials. For the affective tasks (tail flick, open field, and elevated plus-maze), subjects were injected 1 or 24 h prior to testing. DHEA deceased latencies and trials to criterion in the water maze, and decreased motor activity in the open field at 24 h postinjection. DHEAS decreased latencies to the goal arm in the Y-maze and reduced motoricity and the number of entries into the center of a brightly lit open field, both 1 and 24 h after injection. These findings suggest that DHEA and DHEAS may alter performance on cognitive tasks due to motor or anxiety effects.