Behavioural Tasks in Bussey-Saksida Touchscreen Chambers
Bussey-Saksida Touch Screen System, developed by Timothy Bussey and Vina Saksida, is an automated apparatus and method that uses a computer monitor to present stimuli, and an infra-red ‘touch-screen’ assembly with which an animal can register its response. The following cognitive tests are available for use in the platform:
Progressive Ratio And Effort Related Choice Task For Mice
DETAILS
The touch screen version of the PR and ERC tasks are designed to be equivalent to the more usual tasks done with levers and nose pokes. Comparing the touch screen tasks to versions based on levers and nose pokes:
The PR task is very easy and quick to train - typically it takes 16 days to train naïve mice to reach stable PR performance, ready for pharmacological validation.
DESCRIPTION
The mouse has to touch a white square X number of times to receive a reward. X can be the same for all trials (Fixed Ratio) or progressively increase as the experiment proceeds (Progressive Ratio).
The ERC is the same as the Fixed Ratio Task, except food is placed in the chamber, so that the mouse is required to choose between expending physical effort to obtain a highly preferred food or expending much less effort to freely consume less preferred food.The Task suite of programs supplied includes all training schedules and analysis filters.
REFERENCE
Heath CJ, Bussey TJ, Saksida LM., Motivational assessment of mice using the touchscreen operant testing system: effects of dopaminergic drugs. Psychopharmacology, 2015
The touch screen version of the PR and ERC tasks are designed to be equivalent to the more usual tasks done with levers and nose pokes. Comparing the touch screen tasks to versions based on levers and nose pokes:
The PR task is very easy and quick to train - typically it takes 16 days to train naïve mice to reach stable PR performance, ready for pharmacological validation.
- PR performance is very stable across several days (greater stability than has been observed with non-touch screen versions of the task).
- Performance can be modulated bi-directionally with systemic pharmacology so the task is sensitive to both stimulation and inhibition. Using the same compounds as in non-touch screen versions of the task found similar effects, suggesting the touch screen version interacts with the same neurobiological system
- Comparing it to the non-touch screen literature, it appears that the touch screen paradigm
- produces less variable data and consequently easier detection of significant effects.
- is more sensitive to manipulations which promote PR performance and therefore useful for screening of drugs to alleviate low motivation.
- may also be less sensitive to drugs which suppress performance, relative to non-touch screen versions.
- The touch screen ERC task in mice shows the same behavioral performance shift previously reported in the rat lever press literature, suggesting the touch screen version interacts with the same neurobiological systems as the non-touch screen version.
DESCRIPTION
The mouse has to touch a white square X number of times to receive a reward. X can be the same for all trials (Fixed Ratio) or progressively increase as the experiment proceeds (Progressive Ratio).
The ERC is the same as the Fixed Ratio Task, except food is placed in the chamber, so that the mouse is required to choose between expending physical effort to obtain a highly preferred food or expending much less effort to freely consume less preferred food.The Task suite of programs supplied includes all training schedules and analysis filters.
REFERENCE
Heath CJ, Bussey TJ, Saksida LM., Motivational assessment of mice using the touchscreen operant testing system: effects of dopaminergic drugs. Psychopharmacology, 2015
DETAILS
Based on the Iowa Gambling Task, the rodent chooses from four illuminated windows. A touch in any of the windows will result in either a Win (food reward is delivered) or a Loss (a timeout period with no reward). Each window is associated with a different amount of reward. The larger the associated reward, the lower the probability of receiving a Win and the longer the timeout if the trial results in a Loss. The subject must learn to avoid the high-risk, high-reward options in order to maximize earnings. The test is sensitive to serotonergic and dopaminergic agents.
Based on the Iowa Gambling Task, the rodent chooses from four illuminated windows. A touch in any of the windows will result in either a Win (food reward is delivered) or a Loss (a timeout period with no reward). Each window is associated with a different amount of reward. The larger the associated reward, the lower the probability of receiving a Win and the longer the timeout if the trial results in a Loss. The subject must learn to avoid the high-risk, high-reward options in order to maximize earnings. The test is sensitive to serotonergic and dopaminergic agents.
DETAILS
We are pleased to offer rodent versions of the Human CPT task. Task developed by Adam Mar and colleagues at the University of Cambridge in the labs of Trevor Robbins, Tim Bussey, and Lisa Saksida (Kim et al., 2015; Hvoslef-Eide et al., 2015).
CPT tasks have been widely used to assess attentional processes. Attention in rodents is usually tested using the 5-choice serial reaction time task and 5-choice continuous performance tasks. These, however, require spatially divided attention. Typical Human CPT tasks present a series of images, each image being presented in succession for a brief period, in the same position. The subject is required to respond to designated target stimuli and withhold a response to non-target stimuli. This has the added difficulty of being able to discriminate and remember target patters, demonstrated as a key variable for observing vigilance decrements in perceptual sensitivity.
What is the Task?
In the rodent Image CPT task, 5 different black and white images are used. They are shown briefly, one at a time and in a random order, on the touch screen. One of the images is designated the target stimulus. In order to obtain reward, the subject must touch the target stimulus and withhold from touching the non-target stimuli. This task keeps the differences between pre-clinical and clinical attention tasks to a minimum.
As well as offering a CPT task the same as the Human tasks, this task also take less time to train (typically rats take ~20 days from habituation to the chamber, as opposed to 24 weeks for the 5-CPT tasks).
Neural Systems Involved: Dopamine, Serotonin, Colinergic, Parietal, Muscarinic
Clinical area showing impairment: Schizophrenia, ADHD, OCD, Alzheimer's
Reference
Chi Hun Kim, Martha Hvoslef-Eide1, Simon R. O. Nilsson, Mark R. Johnson, Bronwen R. Herbert, Trevor W. Robbins, Lisa M. Saksida, Timothy J. Bussey, & Adam C. Mar. The continuous performance test (rCPT) for mice: a novel operant touchscreen test of attentional function. Psychopharmacology. (2015)
We are pleased to offer rodent versions of the Human CPT task. Task developed by Adam Mar and colleagues at the University of Cambridge in the labs of Trevor Robbins, Tim Bussey, and Lisa Saksida (Kim et al., 2015; Hvoslef-Eide et al., 2015).
CPT tasks have been widely used to assess attentional processes. Attention in rodents is usually tested using the 5-choice serial reaction time task and 5-choice continuous performance tasks. These, however, require spatially divided attention. Typical Human CPT tasks present a series of images, each image being presented in succession for a brief period, in the same position. The subject is required to respond to designated target stimuli and withhold a response to non-target stimuli. This has the added difficulty of being able to discriminate and remember target patters, demonstrated as a key variable for observing vigilance decrements in perceptual sensitivity.
What is the Task?
In the rodent Image CPT task, 5 different black and white images are used. They are shown briefly, one at a time and in a random order, on the touch screen. One of the images is designated the target stimulus. In order to obtain reward, the subject must touch the target stimulus and withhold from touching the non-target stimuli. This task keeps the differences between pre-clinical and clinical attention tasks to a minimum.
As well as offering a CPT task the same as the Human tasks, this task also take less time to train (typically rats take ~20 days from habituation to the chamber, as opposed to 24 weeks for the 5-CPT tasks).
Neural Systems Involved: Dopamine, Serotonin, Colinergic, Parietal, Muscarinic
Clinical area showing impairment: Schizophrenia, ADHD, OCD, Alzheimer's
Reference
Chi Hun Kim, Martha Hvoslef-Eide1, Simon R. O. Nilsson, Mark R. Johnson, Bronwen R. Herbert, Trevor W. Robbins, Lisa M. Saksida, Timothy J. Bussey, & Adam C. Mar. The continuous performance test (rCPT) for mice: a novel operant touchscreen test of attentional function. Psychopharmacology. (2015)
DETAILS
Like the 5-choice serial reaction task, this task requires the rodent to respond to .a brief visual stimulus presented randomly in one of 5 locations. In addition some trials present visual stimuli in all five locations together and for these trials the subject must learn to withhold a response. This go/no-go task measures both attentional and inhibitory systems within a single task paradigm, enabling the assessment of vigilance.
This task was developed for the 5/9 choice chamber and adapted for the Bussey-Saksida touch screen.
Original Reference
Young JW, Light GA, Marston HM, Sharp R, Geyer MA. (2009) The 5-choice continuous performance test: evidence for a translational test of vigilance for mice. PLoS One.; 4(1): e4227.
Like the 5-choice serial reaction task, this task requires the rodent to respond to .a brief visual stimulus presented randomly in one of 5 locations. In addition some trials present visual stimuli in all five locations together and for these trials the subject must learn to withhold a response. This go/no-go task measures both attentional and inhibitory systems within a single task paradigm, enabling the assessment of vigilance.
This task was developed for the 5/9 choice chamber and adapted for the Bussey-Saksida touch screen.
Original Reference
Young JW, Light GA, Marston HM, Sharp R, Geyer MA. (2009) The 5-choice continuous performance test: evidence for a translational test of vigilance for mice. PLoS One.; 4(1): e4227.
DETAILS
The task involves learning that one of two shapes displayed simultaneously on the screen is correct. Touching the correct stimuli (S+) will be rewarded with food. Touching the incorrect stimuli (S-) will be punished with a timeout. Once the task has been learned, the stimuli are reversed so that the S+ stimuli now becomes the S- stimuli and vice versa. This reversal learning requires inhibition of prepotent responses and is known to be dependant on the prefrontal cortex.
The task involves learning that one of two shapes displayed simultaneously on the screen is correct. Touching the correct stimuli (S+) will be rewarded with food. Touching the incorrect stimuli (S-) will be punished with a timeout. Once the task has been learned, the stimuli are reversed so that the S+ stimuli now becomes the S- stimuli and vice versa. This reversal learning requires inhibition of prepotent responses and is known to be dependant on the prefrontal cortex.
DETAILS
In humans a similar task has proved to be highly effective for the early detection of Alzheimer's disease. In the PAL task for rodents, subjects learn and remember which of three objects goes in which of three spatial locations. On a given trial, two different objects are presented; one in its correct location; the other in an incorrect location. The subject must choose which stimulus is in the correct location. The task has been shown to be sensitive to cholinergic transmission and to hippocampal dysfunction and can dissociate glutamate from acetylcholine receptor function in the hippocampus.
In humans a similar task has proved to be highly effective for the early detection of Alzheimer's disease. In the PAL task for rodents, subjects learn and remember which of three objects goes in which of three spatial locations. On a given trial, two different objects are presented; one in its correct location; the other in an incorrect location. The subject must choose which stimulus is in the correct location. The task has been shown to be sensitive to cholinergic transmission and to hippocampal dysfunction and can dissociate glutamate from acetylcholine receptor function in the hippocampus.
DETAILS
This is a habit or stimulus-response task in which the rodent learns a rule of the type "If shape A is presented, respond to the left location; if shape B is presented, respond to the right location". This type of test is sensitive to damage in the dorsal striatum and is therefore relevant to Huntington's and Parkinson's disease.
This is a habit or stimulus-response task in which the rodent learns a rule of the type "If shape A is presented, respond to the left location; if shape B is presented, respond to the right location". This type of test is sensitive to damage in the dorsal striatum and is therefore relevant to Huntington's and Parkinson's disease.
DETAILS
This task requires the rodent to respond to a brief visual stimulus presented randomly in one of 5 locations. This task in rodents is sensitive to cortical manipulations, especially those involving prefrontal cortex, and is highly dependent on cholinergic transmission.
This task requires the rodent to respond to a brief visual stimulus presented randomly in one of 5 locations. This task in rodents is sensitive to cortical manipulations, especially those involving prefrontal cortex, and is highly dependent on cholinergic transmission.
DETAILS
The task measures a Pavlovian response to the screen. This is a very rapidly administered test of simple classical conditioning that is dependent on a reward system centered on the ventral striatum. White vertical rectangles are presented on either side of the reward tray. One side is always followed by delivery of food reward, the other never. Reward is independent of screen approach. Approaches to the screen are measured via an IR beam detector either side of the food tray.
The task measures a Pavlovian response to the screen. This is a very rapidly administered test of simple classical conditioning that is dependent on a reward system centered on the ventral striatum. White vertical rectangles are presented on either side of the reward tray. One side is always followed by delivery of food reward, the other never. Reward is independent of screen approach. Approaches to the screen are measured via an IR beam detector either side of the food tray.
DETAILS
TUNL can be thought of as a version of delayed nonmatching-to-place (DNMTP), in which the subjects are presented with a sample location and, following a delay, with the (incorrect, S-) sample location and a (correct, S+) nonmatching location. DNMTP has been shown to be vulnerable to non-spatial mediating strategies. TUNL eliminates these problems by using multiple, trial-unique locations, preventing the use of mediating strategies. Animals with lesions in the dorsal hippocampus or decreased hippocampal neurogenesis were impaired when the locations were close together, but not when they were far apart. This feature also renders the task exquisitely sensitive to hippocampal dysfunction, tapping both the role of the hippocampus in memory and in pattern separation.
TUNL can be thought of as a version of delayed nonmatching-to-place (DNMTP), in which the subjects are presented with a sample location and, following a delay, with the (incorrect, S-) sample location and a (correct, S+) nonmatching location. DNMTP has been shown to be vulnerable to non-spatial mediating strategies. TUNL eliminates these problems by using multiple, trial-unique locations, preventing the use of mediating strategies. Animals with lesions in the dorsal hippocampus or decreased hippocampal neurogenesis were impaired when the locations were close together, but not when they were far apart. This feature also renders the task exquisitely sensitive to hippocampal dysfunction, tapping both the role of the hippocampus in memory and in pattern separation.
DETAILS
The rodents are required to discriminate between two white squares on the screen. Responses to squares on one side of the screen will be rewarded, while responses on the other side of the screen will be punished with a time out period. The distance between the two squares is varied from trial to trial. Animals with lesions in the dorsal hippocampus were impaired when the locations were close together, but not when they where far apart.
The rodents are required to discriminate between two white squares on the screen. Responses to squares on one side of the screen will be rewarded, while responses on the other side of the screen will be punished with a time out period. The distance between the two squares is varied from trial to trial. Animals with lesions in the dorsal hippocampus were impaired when the locations were close together, but not when they where far apart.
DETAILS
As a measure of impulsivity, the Delay Discounting Task (DD) measures how long the rodent is prepared to wait for a larger reward.
How does it work?
Two stimuli positions are set up with one position giving a small reward after a short delay and the other offering a larger reward after a longer delay. Position, delay, and reward are set by user with the reward positions remaining constant throughout the experiment.
The experiment is split into 4 groups of 12 trials, each group having a progressively longer delay for the larger reward.
As a measure of impulsivity, the Delay Discounting Task (DD) measures how long the rodent is prepared to wait for a larger reward.
How does it work?
Two stimuli positions are set up with one position giving a small reward after a short delay and the other offering a larger reward after a longer delay. Position, delay, and reward are set by user with the reward positions remaining constant throughout the experiment.
The experiment is split into 4 groups of 12 trials, each group having a progressively longer delay for the larger reward.
In Vivo Neural Recording
The platform has the resources to perform both in vivo calcium imaging and intercelular electrophysiololgical recordings simultaneously. Through the use of a variation of the UCLA Miniscope, a miniature fluorescence camera/microscope mounted on the skull, we can monitor and record calcium while also monitoring and/or stimulating specific brain regions electrophysiologically or optogenetically.
We are currently able to reliably record from CA1, CA3, MS, LS, thalamus, striatum, and cortex (see images page) and will explore the possibilities of recording from any structure requested by a researcher.
We are currently able to reliably record from CA1, CA3, MS, LS, thalamus, striatum, and cortex (see images page) and will explore the possibilities of recording from any structure requested by a researcher.
Viral Vectors
Viral vectors are acquired from the following sources:
Addgene: https://www.addgene.org/viral-vectors/aav/
Laval: https://neurophotonics.ca/viral-vector-facility
UNC: http://www.med.unc.edu/genetherapy/vectorcore
UPenn: https://www.med.upenn.edu/gtp/vectorcore/
Addgene: https://www.addgene.org/viral-vectors/aav/
Laval: https://neurophotonics.ca/viral-vector-facility
UNC: http://www.med.unc.edu/genetherapy/vectorcore
UPenn: https://www.med.upenn.edu/gtp/vectorcore/
Data Analysis
Calcium and electrophysiology data are processed using custom adaptations of the following software packages:
CellSort: https://github.com/mukamel-lab/CellSort
CNMFe: https://github.com/balajisriram/cnmfe
Bonsai: http://www.open-ephys.org/bonsai
CellSort: https://github.com/mukamel-lab/CellSort
CNMFe: https://github.com/balajisriram/cnmfe
Bonsai: http://www.open-ephys.org/bonsai
Data Storage and Sharing
Data generated by the platform will be stored in local and offsite servers, and will be open for collaboration.
Compute Canada archive and cloud storage
MouseBytes open access database for mouse cognition, imaging and genomics data integration
Compute Canada archive and cloud storage
MouseBytes open access database for mouse cognition, imaging and genomics data integration