place-and-response-learning-in-the-open-field-tower-maze

Place and Response Learning in the Open-field Tower Maze

This protocol describes how the Open-field Tower Maze (OFTM) paradigm is used to study spatial learning in rodents. This maze is especially useful for ...

Christopher Newport University

Three experiments were conducted using a lick-suppression preparation with rats to determine whether temporal and physical context shifts modulate the effectiveness of 2 sequentially trained blocking stimuli. Experiment 1 ascertained that it is possible to obtain blocking by conditioning rats to react to a target cue using 2 different blocking cues, each trained with a single-phase blocking paradigm. Experiment 2 showed that the more recently trained blocking stimulus was more effective (i.e., showed a recency effect) when testing was conducted immediately after training, but a long retention interval attenuated blocking by the most recently trained blocking stimulus and increased blocking by the initially trained blocking stimulus (i.e., a recency-to-primacy shift). This shift from recency to primacy affected in Experiment 2 by varying the retention interval was replicated in Experiment 3 by changing the physical context between training and testing. Taken together, the results indicate that the effectiveness of sequentially trained competing stimuli follows the same recency-to-primacy shift rule that is seen in traditional interference phenomena.

Recency-to-primacy shift in cue competition.

The striatum receives prominent dopaminergic innervation that is integral to appetitive learning, performance, and motivation. Signaling through the dopamine D2 receptor is critical for all of these processes. For instance, drugs with high affinity for the D2 receptor potently alter timing of operant responses and modulate motivation. Recently, in an attempt to model a genetic abnormality encountered in schizophrenia, mice were generated that reversibly overexpress D2 receptors specifically in the striatum (Kellendonk et al., 2006). These mice have impairments in working memory and behavioral flexibility, components of the cognitive symptoms of schizophrenia, that are not rescued when D2 overexpression is reversed in the adult. Here we report that overexpression of striatal D2 receptors also profoundly affects operant performance, a potential index of negative symptoms. Mice overexpressing D2 exhibited impairments in the ability to time food rewards in an operant interval timing task and reduced motivation to lever press for food reward in both the operant timing task and a progressive ratio schedule of reinforcement. The motivational deficit, but not the timing deficit, was rescued in adult mice by reversing D2 overexpression with doxycycline. These results suggest that early D2 overexpression alters the organization of interval timing circuits and confirms that striatal D2 signaling in the adult regulates motivational process. Moreover, overexpression of D2 under pathological conditions such as schizophrenia and Parkinson's disease could give rise to motivational and timing deficits.

Transient overexpression of striatal D2 receptors impairs operant motivation and interval timing.

Increased striatal dopamine D2 receptor activity is thought to contribute to the pathophysiology of schizophrenia. To model this condition in mice, Kellendonk et al. (2006) generated transgenic mice that selectively overexpress the D2 receptor in striatum (D2OE). Drew et al. (2007) reported that D2OE mice display deficits in interval timing and motivation. The present study further explored the impaired timing in D2OE mice. Experiment 1 assessed the role of motivation in producing timing deficits in the peak procedure and found that performance in D2OE mice was improved by increasing motivation. In addition, performance was impaired in control mice when motivation was decreased. In Experiment 2, we found that D2OE mice have no timing impairment when tested using the bisection task, a procedure in which the measure of timing performance is less influenced by motivation to respond. In Experiment 3, we also used the bisection task and found selective impairment in timing of long durations in D2OE mice. These results suggest that striatal D2 overexpression impairs timing by decreasing motivation and through its impact on working memory and/or sustained attention.

Impaired timing precision produced by striatal D2 receptor overexpression is mediated by cognitive and motivational deficits.

Three Pavlovian fear conditioning experiments with rats as subjects explored the effect of extinction in the presence of a concurrent excitor. Our aim was to explore this particular treatment, documented in previous studies to deepen extinction, with novel control groups to shed light on the processes involved in extinction. Relative to subjects extinguished on the target CS alone, Experiments 1 and 2 found across a range of parameters that any appreciable effect of facilitated extinction due to the concurrent excitor was submerged by generalization decrement going from extinction to testing. In Experiment 3 we used different durations for the target and concurrent stimuli in order to discourage configuring and an ABC renewal design to increase sensitivity, and observed diminished renewal resulting from extinction in the presence of a second excitor. Our findings suggest that there are distinct limits to the observation of extinction in the presence of an excitor and identifies some of the sources of these limitations.

Constraints on Enhanced Extinction Resulting from Extinction Treatment in the Presence of an Added Excitor.

Deficits in incentive motivation, the energizing of behavior in pursuit of a goal, occur in many psychiatric disorders including schizophrenia. We previously reported deficits in both cognition and incentive motivation in a transgenic mouse model of increased striatal-specific dopamine D2 receptor (D2R) density (D2R-OE mice). This molecular alteration is observed in patients with schizophrenia, making D2R-OE mice a suitable system to study the cellular and molecular mechanisms of motivation and avolition, as well as a tool for testing potential therapies against motivational deficits.

Pharmacologic rescue of motivational deficit in an animal model of the negative symptoms of schizophrenia.

Estrogen's (E) involvement in cognition has been difficult to characterize; numerous studies show that E can both enhance and impair learning and memory. One difficulty may be that experimental paradigms often examine only a single aspect of E's involvement in cognition, for example, the role E plays in the expression of memory after learning has taken place. In addition, the effect of aversive and/or stressful features inherent to many cognitive tests may contribute to the contradictory findings. The present experiment aims to examine the effect of estradiol (E2) on several elements of cognition in a specific experimental setting. We investigated the within-subject effects of long-term E2 replacement in ovariectomized (OVX) female rats on the acquisition and retention of a hippocampal-mediated spatial reference memory task in a familiar non-threatening environment. Results show that E2-replaced rats and OVX sham-replaced rats acquired the ability to navigate an open-field tower maze in order to obtain a food reward at the same rate. Subsequent to acquisition, both E2-replaced and OVX rats performed the task at comparable levels. However, following a 21-day retention interval, non-replaced rats exhibited a significant impairment in spatial memory when returned to the maze environment, while E2-replaced rats exhibited no change in maze performance. When the OVX group was performing once again at asymptote, test trials were administered during which the rats were placed in a non-experienced start location within the maze. This novel condition significantly reduced correct responses in E2-replaced females whereas OVX controls remained unaffected. These results suggest that while the presence of E2 is not important for acquisition of spatial memory in a safe familiar environment, it improves retention of spatial memory. Data further suggests that E2 disrupts the expression of spatial reference memory following an alteration of the test conditions sustaining a habitual response, possibly by the induced emotionally-arousing state of stress.

Estrogen enhances the retention of spatial reference memory in the open field tower task, but disrupts the expression of spatial memory following a novel start position.

Estrogen has been shown to either enhance or impair learning and memory in female rats. The use of different experimental paradigms or estrogen treatment regimens may contribute to these disparate findings. In order to assess the effect of different estradiol (E2) treatments on several aspects of cognition, we trained ovariectomized female rats with either continuous, cycling, or vehicle E2 replacement, in an open-field tower maze task (OFTM) designed to test reference memory in a low-stress environment. In addition, in order to compare two distinct learning and memory systems, rats were trained to use either a dorsolateral striatum-based response type learning or a hippocampal-based place type learning to solve the maze. Results showed that cyclic, but not continuous, E2 replacement facilitated the acquisition of spatial memory in place-learners. Neither E2 regimen affected acquisition in response-learners. Additionally, when all experimental groups were performing at asymptote, rats were evaluated for performance stability by changing the location of their start position in the OFTM. Both regimens of E2 disrupted the expression of spatial memory in place-learners following the novel start position. However, E2 replacement protected ovariectomized female rats from the disruption of memory expression following a start position change in response-learners. Additionally all experimental groups performed equally well when tested following a 21-day period during which rats were absent from the maze. These results suggest that E2 fluctuation is particularly important in the acquisition of hippocampal-mediated spatial learning, and that hippocampal-based memory may be subject to disruption following environmental change, while striatum-based memory is subject to protection.

Effects of continuous vs. cycling estrogen replacement on the acquisition, retention and expression of place- and response-learning in the open-field tower maze.

Article	Year
Recency-to-primacy shift in cue competition. Journal of experimental psychology. Animal behavior processes\| PubMed ID: 17044742	2006
Transient overexpression of striatal D2 receptors impairs operant motivation and interval timing. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 17634367	2007
Impaired timing precision produced by striatal D2 receptor overexpression is mediated by cognitive and motivational deficits. Behavioral neuroscience\| PubMed ID: 19634929	2009
Constraints on Enhanced Extinction Resulting from Extinction Treatment in the Presence of an Added Excitor. Learning and motivation\| PubMed ID: 20160908	2009
Pharmacologic rescue of motivational deficit in an animal model of the negative symptoms of schizophrenia. Biological psychiatry\| PubMed ID: 21414604	2011
Estrogen enhances the retention of spatial reference memory in the open field tower task, but disrupts the expression of spatial memory following a novel start position. Neurobiology of learning and memory\| PubMed ID: 23178325	2013
Effects of continuous vs. cycling estrogen replacement on the acquisition, retention and expression of place- and response-learning in the open-field tower maze. Neurobiology of learning and memory\| PubMed ID: 24837787	2014

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