Uncovering Neural Circuits Involved in Motor Learning

Uncovering Neural Circuits Involved in Motor Learning

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)

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Check out the full article in Cell here.

Part V – Tokyo Medical and Dental University

Part V – Tokyo Medical and Dental University

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).

Part IV – We Visit Doshisha University in Kyoto

Part IV – We Visit Doshisha University in Kyoto

While in Kyoto, I traveled to Doshisha University to visit the lab of Dr. Takahashi, who worked with O’Hara to design the Free Maze, a reconfigurable maze for learning and memory tests.

Me with Dr. Takahashi at Doshisha University

Dr. Takahashi studies hippocampal place cell activity in mice and rats, and wanted to build a maze system that he could easily change in order to understand how place cells adapt to changes in environments.

According to Dr. Takahashi, “The Free Maze was designed to be flexible, reliable, and repeatable.”
“We built this maze in order to design a system where users could build their own tasks to their own specifications, change maze designs rapidly, and reconfigure previous designs easily.”

For his research, Dr. Takahashi records population activity of hippocampal place cells in freely moving rats as they navigate through the Free Maze.

The Free Maze is an extremely unique product. It’s like legos for scientists!

The original paper detailing the Free Maze is currently under review and should be available soon.

The Free Maze for Rats

Next stop – Tokyo Medical and Dental University
Mapping Motor Circuit Mechanisms During Voluntary Movement

Mapping Motor Circuit Mechanisms During Voluntary Movement

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!

Abstract Citation

*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

Understanding how the Visual System Influences Perceptual Decision Making

Understanding how the Visual System Influences Perceptual Decision Making

Several users of our O’Hara behavioral testing systems are presenting their research at SfN 2019 this year!
Check out what they’ve been working on.

Benucci and colleagues at RIKEN Center for Brain Science are currently investigating how neural networks in the visual system interact with environmental cues during the decision making process using the Self Head-Restraining Platform for mice. Below is a summary of what they plan to present at SFN2019

The role of neural networks within the visual system in guiding perceptual decision making processes is largely unknown.  Orlandi and colleagues in Dr. Andrea Benucci’s lab hypothesized that neuronal activation in visual cortices was necessary to provide predictive information about either the animals’ choices or task outcome (or both) during the decision making process. To test this, they analyzed calcium signals of GCaMP infected neurons in mice implanted with cranial windows over occipital-parietal cortical areas as they performed a two-alternative forced choice orientation discrimination task (See an example of the task below). By using large cranial windows, Orlandi and colleagues had optical access to between 10-12 cortical areas at the same time, allowing them to visualize signals from large-scale and distributed neural networks within the visual system. What they found was that large-scale activations of occipital-parietal visual areas did in fact hold predictive information about the animal’s decision.

Example of the two-alternative forced choice orientation discrimination task

Self Head-Restraining Platform: An automated platform with voluntary head fixation

Example of GCaMP expression in mouse cortex. Adapted from the Britt Lab at McGill University

To learn more about Benucci’s research application of the Self Head-Restraining Platform, check out his poster at SFN this year! And Stop by our booth # 1502!

Abstract Citation

*J. G. ORLANDI1, S. GRZELKOWSKI2,1, M. ABDOLRAHMANI1, R. AOKI1, D. LYAMZIN1, A. BENUCCI1;
1Lab. for Neural Circuits and Behavior, RIKEN Ctr. for Brain Sci., Wakoshi, Japan; 2FNWI, Univ. van Amsterdam, Amsterdam, Netherlands. Network interactions in the mouse visual cortex are predictive of perceptual decisions. Program No. 751.14. 2019 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2019. Online.

Part III – Kyoto University in Kyoto, Japan

Part III – Kyoto University in Kyoto, Japan

After Tokyo, I took the bullet train to Kyoto University to visit Dr. Watanabe’s lab.

He currently uses both the TaskForcer and the Touch Panel operant chamber for mice. 

Dr. Watanabe is interested in understanding the role of the secondary Motor Cortex in motor planning. He measures a very simple behavior, licking response, which requires just movement of the tongue. For this, Dr. Watanabe designed a custom TaskForcer setup with dual spout ports instead of the single spout-lever. He then created a simple task where animals learn to choose the correct spout (left or right) that varies across trials, in order to receive a liquid reward. In this way, he can examine the role of the Motor Cortex in motor planning, with very little movement of the animal during neurophysiological recording. Regarding the TaskForcer, Dr. Watanabe reiterated, “ With the TaskForcer, I am able to get precise and reliable measurements of neural activity during behavior!”

Me with Dr. Watanable in front of his two-photon imaging setup, where he was currently tracking calcium responses of neurons in the Motor Cortex while a mouse was performing the task.

Next, a few of Dr. Watanabe’s lab members provided a demonstration of the Touch Panel operant chamber for mice. They have three Touch Panel chambers and are currently using them to train mice on a 5 choice serial reaction time task to measure attention. 

Dr. Watanabe plans to record neural activity from freely moving animals using the Touch Panel operant chamber in the future. 

Me with Dr. Watanabe’s lab members in their Touch Panel testing room.

Next stop – Doshisha University in Kyoto!