The TaskForcer and Imaging Adapter Base Mount were designed for simultaneous neural imaging during operant behavior. What’s unique about the imaging adapter base mount is that you can adjust x y and z positions, which allows you to adjust the TaskForcer angle under the 2-photon microscope. This is especially important for making sure the cranial window of the experimental test subject is parallel to the objective. Even slight changes to the angle of the cranial window can offset regions of interest in the imaging window and sacrifice data collection.
The base mount contains mm markings so you can precisely align the TaskForcer unit across experimental sessions that may be spaced days or weeks apart Although the mount was designed for the TaskForcer, it is sold separately and is compatible with a variety of behavioral setups. For more information about the imaging adapter base mount and the TaskForcer check out our TaskForcer product page.
Cranial window implants in head-fixed mice offer stable optical access to large areas of the cortex over extended periods of time. Window preparations can be combined with viral preparations (or in genetically modified mice) to monitor, map or manipulate neuronal activity (eg. using optogenetics) in awake behaving animals. This makes them extremely useful for studying relationships between neuronal activity and behavior.
A major roadblock with the cranial window and optical imaging approach.
The main difficulty with the cranial window and optical imaging approach is the alignment of the mouse or other experimental subjects under the microscope. Due to the curvature of the subject animal’s skull, cranial windows are almost always angled. However, for the most precise optical access, windows should be aligned parallel to the imaging objective. Even minor changes to the window angle can offset neuropil in the axial direction under the microscope and sacrifice data collection. This issue becomes compounded when you repeat experiments over time. Minor changes in the window angle across sessions can distort or change the location of neuropil within the same imaging region, making it challenging to draw significant conclusions from your data.
How can you precisely align the mouse under the microscope each time?
One of AMUZA’s tools, the Imaging Adapter Base Mount on the TaskForcer, overcomes this challenge.
While the mount was made for the TaskForcer unit, it can be made to fit any behavioral rig and enables a more precise fit of your behavioral setup under the microscope.
The Imaging Adapter Base mount can be rotated in X, Y and Z directions to change the angle of your behavioral setup so that you can precisely align the head of the mouse underneath the microscope.
The base mount also contains mm markings, allowing you to get the exact same fit each time you place your behavioral rig under the microscope. This greatly minimizes the chance that observable changes to neuropil are due from distortion of the imaging location under the microscope and greatly improves the quality of your data.
If you are imaging over a wide field of view, the Imaging Adapter Base Mount can be readjusted to align each separate imaging location parallel with your objective. This ensures a consistent level of accuracy across each imaging location.
Each Imaging Adapter Base Mount is custom built to fit your microscope to ensure that you are getting the best product tailored to your specific needs.
In an era of Neuroscience where reproducibility of data is crucial, the Imaging Adapter Base Mount and TaskForcer unit offer stable precision for the most accurate results. You can learn more about this product, and the TaskForcer on our TaskForcer webpage.
Imaging Adapter Base Mount (left) and TaskForcer with base mount (right)
Tanaka and colleagues in Dr. Matsuzaki’s lab at the University of Tokyo have been researching the role of thalamocortical axonal activity in motor learning using the TaskForcer.
Brain regions involved in voluntary movement
The thalamus is a central hub through which neuronal signals are transmitted through the cortex and other subcortical structures including the basal ganglia, the pons, and the cerebellum.
Brain regions involved in voluntary motor control (Adapted from Waxman, SG. Clinical Neuroanatomy 26th edition, 2009).
Together, these structures are involved in controlling voluntary movements like manual skills. In animals, manual skills are learned and refined through repetitive motor learning, which instigates neuronal plasticity in the brain structures involved in these processes.
Measuring axonal activity in vivo
Using two-photon calcium imaging of GCaMP expressing thalamocortical axons in the mouse motor cortex in combination with the TaskForcer restraint operant chamber, Tanaka, et al., ascertained the role of thalamocortical axonal activity in skilled motor learning.
The TaskForcer operant chamber fits under the 2P microscope, enabling precise neural imaging during operant training. The task used was a self-initiated lever-pull task, where mice were trained to pull a lever in order to receive a water reward.
By recording calcium activity of GCaMP expressing thalamocortical axons in the motor cortex during learning, they were able to track the temporal dynamics of thalamocortical activity associated with each stage of the learning process.
Linking neuronal activity to coordinated movements
The authors found that thalamocortical activity was time-locked to both initiation and execution of the lever pull task and that this activity stabilized over time after the initial learning. As proof of concept to verify the thalamus’ role in motor learning, when the authors lesioned the thalamus, lever pull behavior significantly decreased. These results indicated that thalamocortical axonal activity is necessary for motor skill learning, and is more involved during the initial stages of motor skill learning.
Example of the lever-pull task using the TaskForcer. (Adapted from Tanaka et al., 2018)
Upon my return back to Tokyo, I had one final visit with Dr. Isomura at Tokyo Medical and Dental University. He originally developed the TaskForcer for rats with O’Hara over 8 years ago!
Dr. Isomura’s research focuses on understanding information processing in Motor Cortex during motor skill learning. To do this, he performs in vivo whole-cell patch clamp recordings in Motor Cortex as animals learn the lever pull task that was specifically designed for the TaskForcer.
What makes simultaneous neural recording during operant behaviors possible with the TaskForcer is the unique spout-lever. This was specially designed by Dr. Isomura and O’Hara such that the reward (liquid from the spout) and operandum (lever) are combined into one. In this way, the animal can still obtain a reward for pulling the lever even while its body is restrained, allowing for operant learning during simultaneous neurophysiological recording.
Dr. Isomura explains, “Since the animals must learn to perform the lever pull task while under head fixation, we wanted to make sure that the animal could access the reward with minimal head movement, but still be motivated to perform the task.”
Isomura also explains, “We were surprised that rats started pulling the lever the very first day that we put them in the chamber. The lever pull task is very robust. We don’t see animal attrition from failure of animals to learn the task.”
The TaskForcer with a stereotaxic setup in a sound attenuating box.
Me with Dr. Takahashi at Doshisha University
“With the TaskForcer, we can reliably get extremely precise single unit recordings during motor behaviors which allows us to examine causal links between neural activity and behavior in great detail.” – Dr. Isomura
Me with O’Hara team members alongside Dr. Isomura (left).
Several users of our O’Hara behavioral testing systems are presenting their research at SfN.
Matsuzaki and colleagues at the University of Tokyo are investigating the role of primary and secondary motor cortices in information processing during self-initiated versus externally triggered movements. To do this they are using the TaskForcer for mice in combination with in vivo widefield two-photon imaging. Below is a summary of what they plan to present at SFN.
Voluntary motor movements can either be self-initiated, or externally triggered. Neuronal ensembles in the primary (M1) and secondary (M2) both play a role in information processing during voluntary movement, but the relative contribution of each remains unclear. Furthermore, how each region processes information when the same movement is self-initiated (SI) versus externally triggered (ET) remains unknown. Terada and colleagues in the Matsuzaki lab examined whether the pattern of activation differed in M2 compared to M1 during SI and ET movements. They hypothesized that the presence of external stimuli would be sufficient to alter neural activity patterns in M2 when the same movement was self-initiated versus externally triggered. To test this, they trained head-fixed mice to perform a self-initiated lever-pull task (SI) and an external cue-triggered lever-pull task (ET) using the TaskForcer. During task performance, they conducted calcium imaging of GcAMP infected layer 2/3 neurons concurrently in M2 and M1 using super-wide-field two-photon microscopy (Terada et al., 2018) in mice implanted with large cranial windows. They found that the proportion of neurons that responded to movement-related activity specific to either learning type was greater in M2 compared to M1. Furthermore, calcium activity in M2 was differed significantly between the self-initiated and externally triggered trials, indicating that external stimuli are sufficient to drive differential neuronal responses in M2. These results also suggested that M2 can distinguish between learning trials even when the same body part is initiated.
To learn more about Terada and colleagues application of the TaskForcer check out their poster at SFN or visit our booth # 1502!
*S.-I. TERADA1, K. KOBAYASHI2, M. MATSUZAKI1 1The Univ. of Tokyo, Tokyo, Japan;2Natl. Inst. For Physiological Sci., Okazaki, Japan. Neural dynamics in the mouse secondary and primary motor cortices during self-initiated and externally triggered movements. Program No. 081.05. 2019 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2019. Online.
TaskForcer: Restraint Chamber for Operant Conditioning
Amuza team member and product manager for O’Hara Behavioral Testing Solutions, Taylor Clark, travels to Japan to learn more about the applications of O’Hara products from their users.
For over 40 years, O’Hara has been developing and manufacturing equipment for behavioral experiments in Japan. Their products are currently used by over 150 researchers at universities, research institutes, and industrial labs across Japan.
Taylor Clark, Product Manager for O’Hara in the US, traveled to Japan to visit and learn from the researcher’s who have been working with O’Hara products. Her first stop – Tokyo University!
Here’s what she had to say:
First, I had the pleasure of visiting Dr. Masanori Matsuzaki’s laboratory in the Department of Physiology at Tokyo University School of Medicine.
Dr. Matsuzaki’s lab is interested in information processing in the Motor Cortex during motor skills learning. They apply several different techniques including two-photon imaging, optogenetics, and electrophysiology in behaving mice and marmosets to monitor and manipulate neural circuits in Motor Cortex that are involved in the initiation and execution of motor actions.
Currently, Dr. Matsuzaki’s lab is using the TaskForcer in combination with two-photon imaging of mice implanted with cranial windows, in order to monitor calcium dynamics of GCaMP (a genetically encoded calcium indicator) infected neurons in the Motor Cortex during skilled learning.
In speaking with Dr. Telada, assistant professor in Dr. Matsuzaki’s lab about the TaskForcer, here’s what he had to say: “We needed a behavioral apparatus that would allow us to perform longitudinal imaging of the same neuronal populations over time during learning, which is why we chose to use the TaskForcer.”
“With the TaskForcer, we are able to consistently get precise neural recordings during imaging sessions while the mice perform a manual lever pull task.”
“We have now been using the TaskForcer in combination with a custom made two-photon microscope we built that enables super wide-field imaging. This has allowed us to simultaneously image neurons in both primary and secondary motor cortices during motor skills learning.”
Pictured is their TaskForcer setup underneath a two-photon microscope
To learn more about Dr. Matsuzaki’s research, check out his lab’s website.
To see selected publications using the TaskForcer please visit our TaskForcer product page.
Stay tuned for an update from my next destination!