- Chamber
- Odors included
- Digging mediums
The IDED chamber for the attentional set shifting task for mice and rats includes a chamber for convenient testing of individual rodents. The kit comes complete with the entire medium and odor set for testing up to 500 Trials. Convenient and easy to clean ceramic cups (8) allow for multiple tests and rotating chambers before cleaning in the testing in the chamber.
Digging Odor kit comes with the following odors: Nutmeg, Rosemary, Cinnamon, Clove, Red thyme, Ginger, Vanilla, Lemon, Raffia, Foam
Digging Medium Kit comes with the following mediums: Felt, Paper, PomPoms, Sequins, Pipecleaners, Googly eyes, Ribbons, Metallic Strips, Citronella
Odor Kit (Included)
Medium Kit (Included)
The Attentional Set Shifting Task (ASST) is a great tool to probe attention and cognitive flexibility in rodents mediated by the prefrontal cortex. The ASST was developed with respect to one of the most used neuropsychological tasks: The Cambridge Neuropsychological Test Automated Battery (CANTAB) that measures the intradimensional/extradimensional set shifting behavior to evaluate cognitive impairments in humans and non-human primates (Rock et al. 2013).
In rodents, the dimensions used to design the IDED task are odor and medium. Essentially, the animal is trained to associate and pay attention to a particular condition while disregarding the other, considering it as insignificant. When researchers reverse or change the conditions, this, in turn, requires the animal to use their executive functions to find the reward.
The dimension (odor or medium) which is to be associated with reward is determined a priori by the researchers. This dimension is used for both training and testing conditions. In order to determine whether the animal is cognitively flexible or not, the researchers switch the test conditions such that the reward will be associated with the alternate dimension, thus challenging the animal to update their behavior and knowledge.
An attentional set is formed when a subject learns to associate a set of rules to differentiate relevant from irrelevant cues. For instance, the animal learns to associate digging medium (supposed as a relevant cue) with the food reward disregarding the odor (supposed irrelevant cue). In subsequent trials, this association is reinforced; the type of digging medium and odor fluctuates, but the paired associated between medium and reward is kept intact. This reinforced rule turns into a cognitive set (Heisler et al. 2015).
Cognitive flexibility can be assessed by:
Usually, it is harder to learn the new conditions for a reward under the ED trial. It is even more challenging for animals with cognitive or pre-frontal impairments. Thus, by using animals, the IDED task chamber can create a scenario for testing the animals’ cognition based on their ability to override learned behaviors. The model works by teaching the mice the attentional set-shifting task and then presenting them with a variety of situations requiring the mice to modify or update the learned behavior.
A large number of neuropsychiatric and neurodevelopmental disorders are associated with subsequent cognitive impairments which interfere with adaptation and information processing due to inflexibility. For example, despite being distinct clinical conditions, depression, autism spectrum disorder, and schizophrenia are all interlaced with cognitive deficits. Cognition is also impaired in Parkinson’s disorder, autism spectrum disorders, and obsessive-compulsive disorder. The list goes on.
Researchers and scientists that wish to address the cognitive dysfunctions across disease models can do so by incorporating the IDED task chamber into their experiments. By using animal models with the IDED task chamber in pre-clinical studies to play out situations which require cognitive flexibility and response modification, it is possible to study the effects of certain interventions within a controlled, low-risk setting.
2.1. Origin
The Attentional set-shifting task was first introduced by Jennifer Birrell and Verity Brown, 2000 to study the effects of prefrontal lesions on rats’ behavior. Since the very inception, it has been accepted as a solid method for studying cognitive flexibility in animal models (Garner et al. 2006).
Birrell and Brown, 2000 conducted a simple discrimination (SD), a compound discrimination (CD), a reversal of the CD (CDR), an intra-dimensional shifting (IDS) and an extra-dimensional shifting (EDS). In their experiment, during the EDS task, it took the rats with lesions significantly more trials to reach the criterion than the control rats. These results indicate that rats with bilateral lesions of the medial frontal cortex have selective impairment in shifting of attentional set.
The rats with lesions and the control rats were able to learn the basic discrimination tasks and the intra-dimensional shifts without significant differences. But, when performing on the ED task, the lesioned rats took twice as many trials to reach criterion, thus demonstrating the effect of a lesioned pre-frontal cortex when it comes to attentional set-shifting.
A key finding is a sharp distinction between the data obtained from the ID and data from the ED dimensions, demonstrating internal validity (Garner et al., 2006). The same phenomenon can be observed in humans with impaired cognition. The fact that the ED condition requires more learning and effort demonstrates that the animal has difficulty set-shifting into a new, distinct dimension. If this was not the case, the data for the ED condition would not have been significantly different from the data gathered from the ID condition.
2.2. Developments
Since then, an array of experiments has been conducted with the help of the IDED chamber apparatus, demonstrating its versatility and usefulness.
2.3. Recent Development
Recently, A. Cybulska-Klosowicz et al. 2017 utilized the IDED chamber to probe the involvement of the Dopamine system in controlling the executive function. Although, the rodents model of attentional set-shifting is prevalent from the beginning of this decade. A. Cybulska-Klosowicz et al. 2017 discovery that dopamine imbalance particularly deficit disrupts the executive function, especially attention may open new avenues in developing novel interventional strategies in treating neurodegenerative and neuropsychiatric disorders.
The ID/ED Task Chamber consists of two chambers, a testing area, and a waiting area. A guillotine-like start gate regulates the entry to the testing area. The testing chamber is further divided into two compartments with the aid of an acrylic partition. Each chamber in the testing area contains a ceramic bowl that can be filled with the digging medium and the odorant which can be selected from the odor and medium kits.
The separation between the waiting area and the testing area allows for easy preparation of the testing area. Each trial requires a “restart” in which the animal is returned to the waiting area. As soon as the start gate is lifted, the animal gains access to the testing area.
In general, the Attentional Set Shifting task comprises five discrimination phases/conditions: a simple discrimination (SD), a compound discrimination (CD), a reversal of the CD (CDR), an intra-dimensional shifting (IDS) and an extra-dimensional shifting (EDS).
5.1. Preparatory Handling (Days 1-8)
5.2. Food Restriction Period (Days 9-12)
5.3. Acclimation Period (Days 13-14)
5.4. Training (Day 15)
The testing period starts simply and gradually builds up with stimuli and cues.
5.5. Testing Period (Day 16-17)
Note: When adding the odor, give some time for the strong smell to air out a bit because strong odors are repulsive to rodents. The scent needs to dissipate slightly before being added to the testing chamber.
The Attentional Set Shifting Task (ASST) Chamber can be used to measure cognitive flexibility and attentional set shifting. The neural circuits involved in the attentional set-shifting can be assessed by lesioning the prefrontal cortex, dorsolateral prefrontal cortex, or orbitofrontal cortex. The IDED task presents a series of discrimination problems which require the animal to learn rules, then change their behavior when the rules change.
Cognitive flexibility is measured by reversal (CDR) and extra-dimensional shift. Reversal learning challenges the animal’s flexibility in that it must maintain the attentional set while altering the rule learned from a previous stage (CD). For example, if in the CD stage within the odor dimension, paying attention to the nutmeg odor was rewarded, and the rosemary odor had no reward; the reversal (CDR) would also be with the odor dimension, but attention to the rosemary odor would now be rewarded, rather than to the nutmeg odor. In extra-dimensional shift, the formation of an attentional set is challenged when the irrelevant dimension becomes the relevant dimension.
Typically, animals with lesions in the prior mentioned prefrontal areas take longer to learn the new rules and make more errors as their cognitive flexibility is impaired.
Furthermore, assessing the distinction between the ID and ED response yields information pertaining to the brain regions involved. One of the biggest advantages of this method is that you can closely study how certain neurotransmitter systems and modulators impact observable behavior and cognition.
Researchers by and large agree that the reversal phase of the task is highly mediated by the orbitofrontal cortex, while the ED tasks are governed by the medial and lateral prefrontal cortex (Scheggia et al., 2014). You can hone in on these regions and study how your treatment or intervention impacts the relevant neuroanatomy in parallel with observable behavior.
Title | Authors, Year published, Journal | Apparatus | Animals | Disease model | Outcome |
“Medial frontal cortex mediates perceptual attentional set shifting in the rat.” | Birrell & Brown, 2000. Journal of Neuroscience. | Plastic cage (400 x 70 x 18 cm), panels made out of Plexiglas. | 24 Lister Hooded rats | Lesions | Rats with lesions needed twice as many trials for ED shift to reach criterion |
“Glutamate receptor binding in the frontal cortex and dorsal striatum of aged rats with impaired attentional set-shifting.” | Nicole & Baxter, 2003.
European Journal of Neuroscience |
Plastic cage (400 x 70 x 18 cm), panels made out of Plexiglas. | 26 male Long-Evans rats
Young rats: 4-5 months old, Old rats: 27-28 months old |
Aging | Explored physiology of aging on striatum’s NMDA receptors as a function of aging. |
“Comparison of haloperidol, risperidone, sertindole, and modafinil to reverse an attentional set-shifting impairment following sub chronic PCP administration in the rat- a back translational study.” | Goetghebeur & Dias, 2009.
Psychopharmacology |
44 x 64 x 30 cm black, opaque test box.
The floor was punctured with holes, in order to decrease the mixing of odors
11cm in diameter terracotta pots |
Adult male Lister Hooded rats | Phencyclidine (PCP) treated rats as model for schizophrenia | ED deficit reversed by sertindole and modafinil drug administration only |
“The effects of NMDA receptor antagonists on attentional set-shifting task in mice.” | Kos et. al, 2011.
Psychopharmacolgy |
U-shaped black acrylic maze.
39 x 39 cm
Wire grid floor
Containers were glass dishes, 5 cm diameter |
Male C57BL/6J mice
Aged 7 to 8 weeks
Approximate weight 24 g |
Impaired learning by blocking the NMDA receptor NR2B subtype with ketamine | Ro 25-6981 reverses debilitating effect of ketamine making mice perform comparably to controls |
“Impairment of intradimensional shift in an attentional set-shifting task in rats with chronic bilateral common carotid artery occlusion.” | Kim et. al, 2016.
Behavioural brain research |
Opaque acrylic box
50 x 37.5 x 25 cm
Black sliding door
Ceramic pots 7 cm in diameter, 3.5 height |
20 male Wistar rats
10 weeks old |
Chronic bilateral common carotid artery occlusion (BCCAo) comparable to Vascular Dementia (VaD) | Demonstrated validity and parallel physiological outcomes between animal model and Alzheimer’s |
“An Operant Intra-/Extra-dimensional Set-shift Task for Mice” | Scheggia & Papaleo, 2016.
Journal of Visualized Experiments |
New model and development. Presents 3 different perceptual dimensions (olfactory, visual, and tactile stimuli) as opposed to the typical 2. Includes an automatic sliding door controlled by infrared photobeams. The chambers are 16 x 16 x 16 cm and are separated by a plastic door. | C57BL/6J mice
Aged 3 to 7 months |
None | Effectively demonstrates validity and consistency of new chamber |
Human neurodegenerative diseases and other neurological disorders have been known to have a significant effect on the cognitive processes of forming, maintaining and shifting attentional set, which are mediated by the frontal cortex in mammals and can be modulated by pharmacological manipulation (Kesner and Churchwell 2011; Chudasama 2011; Dalley et al. 2004; Robbins 2000; Miller and Cohen 2001).
Understanding, not only the cause but also the effects of the dysfunction arising from human neuropsychiatric disorders (such as schizophrenia, attention-deficit/hyperactivity disorder, and addiction) and neurodegenerative diseases (such as Alzheimer’s and Parkinson’s diseases) is vital in developing effective treatments to restore cognitive performance. Although the dysfunctions may appear superficially similar, the pathology associated with each disorder and diseases differ. Thus a successful assessment and treatment should be tailored with an overall understanding of the pathology, specific dysfunctional aspects of cognitive flexibility and discerning judgment of the affected cognitive processes (Brown et al. 2016).
Below are some examples of how the IDED chamber has been used to study behavior upon drug administration.
5-HT6 receptor antagonist: SB-399665
In a 2005 study by Hatcher et al., it was demonstrated administering the 5-HT6 receptor antagonist, SB-399665, in rats greatly decreased their amount of errors when compared to a controlled group. Furthermore, the 5-HT6 receptor antagonist virtually eradicated any delays or errors when completing the ED portion of the experiment, signifying the drug’s potency in affecting this attentional system.
Desipramine
Rats’ performance on the attentional set-shifting test significantly improved when they were chronically administered desipramine (DMI). The treated rats’ showed a decrease in total errors and their performance on the extradimensional component of the task was significantly better.
DMI is an antidepressant drug that works as a selective norepinephrine reuptake inhibitor. In addition to performing the standard experiment, microdialysis was conducted on these rats to measure the extracellular levels of the neurotransmitter norepinephrine in the medial prefrontal cortex.
Thanks to the DMI, the extracellular norepinephrine levels increased in parallel to cognitive flexibility as measured by the rats’ performance (Lapiz, Bondi, & Morilak, 2007).
Ketamine & Ro 25-6981
Ketamine interferes with learning due to its antagonistic effect on NMDA receptors which are crucial for learning. Ketamine consistently impairs the animals’ performance by increasing both their errors and time per task.
The deficits attributable to ketamine can be reversed by administering Ro 25-6981, making the animals’ performance comparable to those of the control group (Kos et al., 2011).
Tolcapone
The prefrontal cortex, as stated earlier, is a major contributor to successful attention. A particular gene, the catechol-O-methyltransferase (COMT) gene, influences the prefrontal cortex by mediating relevant enzymes. However, even though it is clear that there’s catecholaminergic involvement, the neurotransmission mechanism between the COMT gene and subsequent behavioral performance has remained unclear.
To investigate the relationship between the COMT gene, drugs, and performance, a study was conducted on rats that needed to complete the IDED task.
Administering tolcapone, a drug typically given to Parkinson’s patients increases rats’ performance for ED set shifting which otherwise would have remained impaired due to a poorly functioning COMT gene. Upon performing microdialysis on rats that were given tolcapone, the extracellular levels of dopamine were significantly higher in the medial prefrontal cortex (Tunbridge et al., 2004).
Sertindole & Modafinil
In 2008, Goetghebeur and Dias conducted an experiment comparing the effect of various drugs on phencyclidine (PCP) treated rats which serve as a model for schizophrenia. The study had four different groups, each group being assigned to a different drug. Out of the multiple conditions, only the PCP-induced rats that were given sertindole or modafinil displayed improvement in reversing the ED deficit.
Nicotinic Acetylcholine receptor agonists
Nicotine-induced improvements in different aspects of cognitive function (including memory and attention) have been successfully demonstrated in studies involving both humans and experimental animals. Since prefrontal cortex is said to have pronounced involvement in the modulation of cognitive processes and executive functions, efforts have constantly been made to understand how attentional processes are enhanced by nicotine acting at nicotinic acetylcholine receptors.
In experiments conducted by Allison et al. 2013, it was observed that when the subject was injected with nicotine, both acutely and following repeated pre-exposure, there was a significant improvement in Intra-dimensional (ID) and Extra-dimensional (ED) set-shifting performance in the task. Administration of varying dosage of nicotine (0.05 mg/kg, 0.1 mg/kg and 0.2 mg/kg) also revealed that attentional flexibility is dose-dependent.
In an another study aimed to understand effectiveness of activation of nAChRs with selective nicotinic receptor agonists in treatment of cognitive deficits observed in schizophrenia (Wood et al., 2016) as an extension of the aforementioned study, the results showed the advantage of targeting nAChRs to enhance cognitive flexibility, especially the α7 and β2* receptor subtypes. Compound A (α7 nAChR agonist) showed to enhance the subject’s ability in switching between ED set shifting selectively while the α7 nAChR agonist SSR180711 showed improvement in EDS when tested in a smaller dose (3 mg/kg). On the other hand, the selective β2* nAChR agonist 5IA-85380 and nicotine showed improved cognitive between both ED and ID set shifting.
Positive allosteric modulator and α7 nicotinic acetylcholine receptor partial agonists
The Positive allosteric modulator, 3‐furan‐2‐yl‐N‐p‐tolyl‐acrylamide (PAM‐2) was shown to be a potential candidate for the treatment of cognitive disorders when tested for pro-cognitive activity in conjunction with α7 nAChR receptors DMXBA and A-582941 (Potasiewicz et al. 2015). Post hoc analysis, after attentional set-shifting task, revealed that the subject’s cognitive flexibility was specifically enhanced by acute administration of DMXBA (1.0 mg•kg−1), A-582941 (0.3 and 1.0 mg•kg−1), and PAM-2 (1.0 mg•kg−1). It was also observed that co-administration of PAM-2 with either DMXBA or A-582941 facilitated cognitive performance. PAM-2 was also shown to reverse object recognition impairment induced by scopolamine.
Common measurements for the attentional set-shifting task include:
Trial duration: The time it takes to complete the task on average or “trial duration” is frequently measured and assessed within this experimental set-up.
Latency to respond: can be recorded with a modified version of the maze which contains nose-poke holes. The time (in seconds) it takes from opening the start gate to the rodent poking its nose through the holes is recorded.
Attentional set-shifting is defined as the ability to transition between cognitive-attentional sets and has been used as a measure of cognitive flexibility and executive functions over six decades in the investigation of human cognition. Wisconsin Card Sorting Test (WCST) and a more recent refined version of intra- and extra-dimensional attentional set-shifting (ID/ED) of the CANTAB have been extensively used in neuropsychological tasks for measuring attentional set-shifting and cognitive flexibility, and in identifying specific cognitive abnormalities in a wide range of mental disorders in humans.
The IDED task modified for animals has high predictive value and construct validity, making performance comparable to those attentional set-shifting tasks which are performed by humans (Birrell & Brown, 2000).
In a schizophrenic mouse model, for example, to determine whether mice would perform comparably to schizophrenic patients on the ASST, the mice were administered phencyclidine (PCP), a drug used for inducing a schizophrenic model, and then measured based on the IDED tasks. The mice in the 1.3 mg/kg of PCP condition displayed poor performance when it came to the extra-dimensional shift task results which parallel those in human schizophrenic patients (Laurent & Podhorna, 2004).
9.1. Strengths
9.2. Limitations
It can be confusing to keep track of the experimental conditions, which stimuli indicate what, when to reverse, etc. The key is to stay organized and to keep your charts, notes, and experimental outline with you.
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