Discovery of subdivisions in rat motor cortex has potential to advance human brain studies
Sensory-motor transformations in rat motor cortex; from collaborative work between Jared Smith, Kevin Alloway, and Patrick Drew. Credit: Alloway Lab, Penn State.
By: Seth Palmer
This article is the second of a series exploring the diversity of interests and variety of experimental approaches represented by neuroscientists at the Huck Institutes.
Investigating subjects ranging from neural response and habituation to alcohol, to mechanisms of motor control, to effects of neural injury, these researchers are devising unique methodologies employing a wide variety of technologies and techniques, and they are making discoveries with the potential to change the way we experience our world.
Neuroscientists face a multitude of challenges in their efforts to better understand the human brain, and were it not for model organisms such as the rat, they might never know what really goes on inside our heads.
Comprising somewhere between 1014 and 1015 synapses formed by roughly 100 billion neurons, the brain is a phenomenal processor that in a year's time can generate roughly 300,000 petabytes of data — 30,000 times the amount generated by the Large Hadron Collider — and trying to decipher its signals without an abundance of human subjects volunteering to have chips and electrodes implanted in their brains is, to say the least, a daunting prospect.
But particularly for individuals who have lost a limb or been partially or fully paralyzed, this work is a critical pursuit with potentially life-changing results — enabling such amazing biotechnological advances as the development of a brain-computer interface for controlling prosthetic limbs.
Such devices require a detailed understanding of the motor cortex, a part of the brain that is crucial in issuing the neural commands that execute behavioral movements, and a recent paper published in the journal Frontiers in Neural Circuits by Jared Smith and Kevin Alloway — researchers at the Penn State Center for Neural Engineering and affiliates of the Huck Institutes of the Life Sciences — details their discovery of a parallel between the motor cortices of rats and humans that signifies a greater relevance of the rat model to studies of the human brain than scientists had previously known.
“The motor cortex in primates is subdivided into multiple regions, each of which receives unique inputs that allow it to perform a specific motor function,” said Kevin Alloway, a professor of neural and behavioral sciences and a distinguished educator at the College of Medicine at Penn State. “In the rat brain, the motor cortex is small and it appeared that all of it received the same type of input. We know now that sensory inputs to the rat motor cortex terminate in a small region of the motor cortex that is distinct from the larger region that issues the motor commands. Our work demonstrates that the rat motor cortex is parcellated into distinct subregions that perform specific functions, and this result appears to be similar to what is seen in the primate brain, where parietal and prefrontal inputs terminate in separate regions that regulate completely different motor functions.”
Neuroscientists rely on model organisms such as the rat as a means of understanding the brain's basic mechanisms. Without an abundance of human subjects, scientists' next-best option for research is our closest relative, the chimpanzee; but since primate research is highly restricted, controversial, and prohibitively expensive, scientists often turn to studying other model organisms such as the rat. In many instances, data obtained from these model organisms can be translated to primate models and then to humans; but in such cases, scientists must make certain ethological considerations to ensure the validity of their conclusions.
"It's important whenever you study other animals, such as rats, that you see the world through their experience...'walk a mile in their paws,' so to speak,” said Jared Smith, a Penn State graduate student in the Huck Institutes' Neuroscience program and the first author of the paper. "You have to take into account the animal's natural behaviors to best understand how their brains are structured for sensory and motor processing. For primates like us, that means a strong reliance on visual information from the eyes, but for rats it’s more about the somatosensory inputs from their whiskers."
In fact, nearly a third (~30%) of the rat’s sensorimotor cortex is devoted to processing whisker-related information, even though the whiskers' occupy only a third of a percent (0.3%) of the rat's total body surface; similarly in humans, nearly 40% of the entire cortex is devoted to processing visual information even though the eyes occupy a very tiny portion of our body’s surface.
Methodology and results
To understand the structure and function of the rat motor cortex, Smith and Alloway conducted a series of experiments focused on the medial agranular region, which responds to whisker stimulation and elicits whisker movements when stimulated.
"Our research,” said Smith, “was conducted in two stages to investigate the functional organization of the brain: first tracing the neuronal connectivity, and then measuring how the circuits behave in terms of their electrophysiology. Just like in any electrical circuit, the first thing you need to do is trace the wires to see how the different components are connected. Then you can use this information to make sense of the activity going on at any particular node. In the end, you can step back and see how all the circuits work together to achieve something more complex, such as motor control."
To determine where whisker-related information was being processed in the rat brain, Smith and Alloway used anterograde tracers — chemicals that can be transported along nerve pathways — to track the routes of neuronal projections to the motor cortex.
Then, to determine if the target regions of those projections processed sensory input or motor output information, Smith and Alloway used a technique called intracortical microstimulation (ICMS) — which involves stimulating a group of neurons with a small electrical current passed through a microelectrode — to induce twitches in the muscles that move the rat's whiskers. The muscle twitches were recorded by an electromyograph — which detects electrical potential generated by muscle cells — and when the resulting data were analyzed with the help of Patrick Drew, an assistant professor of engineering science and mechanics (ESM) and neurosurgery at Penn State, they appeared to indicate that there were several functionally distinct subdivisions in the rat motor cortex.
“By combining neuronal tracing with neuronal recording and microstimulation techniques,” said Alloway, “we discovered different sensory input regions that were distinct from the region that issued the motor commands to move the whiskers. In this respect, we were fortunate to have Patrick Drew help us analyze the EMG signals produced by microstimulation because this showed that the sensory input region was significantly less effective in evoking whisker movements.”
"This was really surprising to us,” Smith added, “but the results explained some discrepancies that had popped up in other studies from our lab and also across the field. Researchers tended to view each representation in the rat motor cortex, such as for whiskers or forelimbs, as being uniform. What these data show is that there are functionally distinct regions, within the whisker representation at least, which result in profoundly different processing by adjacent and seemingly similar neurons."
As a result of Smith and Alloway's discovery, previously published data on the rat motor cortex can be revisited with a new degree of specificity, and more similarities between the brains and neural processes of rats and humans may eventually come to light, perhaps even informing studies of other model organisms.
But whatever additional results may be realized or not, this discovery is nonetheless one that is sure to advance the study of the human brain in ways no one has yet foreseen.
"This study is by no means the end of the story,” said Smith, “and it opens up avenues for studying some very complex neural processes in rodents that are more like our own then we had previously thought. The tools now available for studying activity in the rodent brain are improving at a remarkable pace, and the findings are even more interesting as we discover just how similar these mammalian relatives are to us. This is a very exciting time in neuroscience."
This research was supported by a grant from the National Institutes of Health.
More about the researchers
- Jared Smith is conducting his research in the Millennium Science Complex as part of a dual appointment between the Department of Neural and Behavioral Sciences at the College of Medicine in Hershey and the Center for Neural Engineering at University Park. He is advised by Kevin Alloway.
- Patrick Drew is a faculty member of the Huck Institutes' graduate programs in cell and developmental biology, neuroscience, and physiology, and a member of the Center for Neural Engineering.
- Kevin Alloway is a faculty member of the Huck Institutes' Neuroscience graduate program, and his lab is located at the Center for Neural Engineering in the Millennium Science Complex.
- Smith JB
- Alloway KD
- Rat whisker motor cortex is subdivided into sensory-input and motor-output areas
- Frontiers in Neural Circuits 7(4)