A General Overview of Locomotor Activity

Next time you take out your dog for a walk or find yourself strolling down the potato chip aisle, try to wonder how exactly all of that happens. These simple, basic locomotor activities are, in fact, quite complicated and elusive to scientists.

Walking is one of life’s cradles, enabling proper everyday functioning. Yet, the precise mechanisms involved behind it remain largely unknown, with only some pieces gathered here and there.

So, what do researchers know? And how did they get there? Well, let’s find out!

Models and Theories on Locomotor Activity

Walking and motion are coordinated events which involve alternating the halves of the body to be in excited or inhibited states, in order to create fluid propulsion and momentum.

In an effort to get closer to the truth, the following theories have been proposed by scientists to explain locomotor activity. But, a large question mark remains and more research definitely needs to be conducted!

The general understanding is that forelimbs and hindlimbs belong to independent circuits and their coordination comes from the interaction between rhythm-generating excitatory neurons and pattern-generating neurons.

Yet, when it comes to defining just how these neurons interact to create a coordinated, rhythmic output, a consensus is lacking.

The following models are currently available for describing how locomotor activity is rhythmically coordinated:

• The classical half-center model describes all walking as extensor and flexor bursting which occurs as a result of “two reciprocally coupled half-centers”.
• The flexor burst generator model, on the other hand, explains locomotion through a “flexor burst generator” which can excite flexor motor neurons and inhibit extensor motor neurons.
• The unit burst generator model proposes a slightly more complex explanation for locomotor activity, as a result of the acquiring evidence that a central pattern generator exists. The idea here is that distinct, separate modules can create a rhythm within neighboring muscles which are located around a joint; a system known as the unit burst generator. Then, these unit burst generators (which create local rhythmic patterns and activity) combine to form a network with multiple, interconnected rhythm generators.

The Importance of Locomotor Activity

In humans, locomotor activity is basically the motion and movement required to get from one place to another. How else could we get up from the couch and go get the remote controller that somehow made its way across the room?

But, perhaps more importantly than that, locomotor activity is intricately intertwined with complex human activities, such as:

• Learning
• Motivation

Locomotor activity is necessary for approaching or avoiding a target, stimuli, or big-picture goals. These tendencies (of seeking or avoiding) are at the core of the human experience, of understanding motivation and learning.

Research Techniques for Studying Locomotor Activity

Thus far, a combination of research techniques have been used, in hopes of understanding the nature of locomotor activity, such as:

• Microlesion Studies: By creating lesions (selective damage to particular areas) scientists can get a closer look at how that area is involved in a certain behavior (such as locomotor activity). The assumption here is that by creating small, local damage, any measured deficit thereafter can be attributed to that specific area.
• Afferent Perturbation Studies: Afferent neurons are crucial for stimulating locomotor activity. Some are even involved in regulator phase-transitions and can “reinforce ongoing muscle activity in the extensor phase of the step cycle” ^[1]. Furthermore, afferent inputs give the central pattern generator (CPG) information, so both are closely related in network structure. By focusing on the afferent neurons (through the use of afferent perturbation studies), scientists can gain a greater understanding of CPGs.
• Deletion Studies: By altering the genetic makeup of laboratory animals, scientists use deletion studies to determine how certain genes affect observable behavior such as locomotor activity.
• Pharmacological Activation of the Spinal Cord: The use of drugs and pharmacological substances is another known venue for studying locomotor activity. By administering certain classes of drugs, such as agonists or antagonists, a scientist can get a clearer picture of how the locomotor network layout works. One study demonstrated that the noradrenergic system most readily brings a locomotor rhythm and that alpha-2 agonists (such as clonidine) are more powerful in complete spinal cats ^[2].
• Genetic Ablation Studies Like Optogenetics: Genetic ablation has been a popular, contemporary method for testing locomotor activity. Genetic ablation studies involve changing a particular part of the DNA, whereas deletion studies have a part of the DNA removed (not copied).

And, thanks to these studies, the models and theories of locomotion (eg: the classic- center model) were developed.

The Applications of Locomotor Activity

Locomotor activity is intricately implicated in countless of areas of life. Common areas of interest or reasons that scientists study locomotor activity include:

• To better understand the endogenous timing system.
• To observe the effects of pharmacological intake on locomotor activity ^[3] in skeletal muscle diseases by using behavioral tests such as open field ^[4].
• To determine whether locomotor activity can serve as an index for self-administrated, addictive drugs ^[5].
• To study locomotor changes in neuropsychiatric conditions such as Schizophrenia ^[6].

Locomotor Activity and Pharmacological Studies

Pharmacological treatment and administration can be studied by taking a closer look at locomotor activity. In fact, pharmacological studies frequently assess whether particular drugs affect locomotor activity, inducing either hyper- or hypo- movement.

Another interesting approach is taking a developmental stance and seeing how drug administration during the early stages of development can influence behavior and functioning during later stages of life.

One such study observed how early antipsychotic treatment (using aripiprazole, olanzapine, and risperidone) will later have on adult behavior, using both males and females ^[7]. The researchers found that early olanzapine and risperidone treatment led to hyper-locomotor effects in the forced swim and open-field tests in male rats. On the other hand, olanzapine treatment by itself led to hypo-locomotor effects in male rats during the forced swim test.

Understanding the Central Nervous System With Locomotor Activity Testing

In 2015, a study by Erta et al. used transgenic mice to study the importance of interleukin-6, a very important cytokine produced by astrocytes ^[8]. The researchers made use of the hole-board test and the morris water maze test, as well as many other tests, in order to determine what effect the cytokine interleukin-6 has.

Mice that had interleukin-6 knocked out from their astrocytes were significantly less active in the hole-board test, demonstrating less exploratory activity and not poking their heads in the holes as frequently as the control mice did.

Genetic Studies Relying on Locomotor Activity Testing

Locomotor activity testing is also incredibly handy for genetic studies. For example, one study taking a closer look at the 22q11.2 deletion syndrome demonstrated that mice with the DGR2 gene knocked out displayed poorer coordination during the rotarod test. The results suggest that the motor control enabled by DGCR2 is somehow related to Purkinje cell function ^[9].

Conclusion

With all of its complexity and mystery, locomotor activity is an important behavior studied and addressed by scientists.

There are many tests available for which locomotor activity can be measured and assessed. From treadmiles to parallel rod tests, a wide array of information can be acquired to supplement a particular study type, such as deletion or pharmacological studies.

Given the importance of locomotor activity and its deterioration in diseases, behavioral studies are crucial, in order to progress scientific understanding and create therapeutic relief.

References

1. Ferrell, William R., and Uwe Proske, eds. Neural control of movement. Springer Science & Business Media, 2012.
2. Marcoux, Judith, and Serge Rossignol. “Initiating or blocking locomotion in spinal cats by applying noradrenergic drugs to restricted lumbar spinal segments.” Journal of Neuroscience 20.22 (2000): 8577-8585.
3. Pierce, R. C. and Kalivas, P. W. “Locomotor Behavior.” Current Protocols in Neuroscience 40:8.1 (2007): 8.1.1-8.1.9
4. Tatem, Kathleen S., et al. “Behavioral and locomotor measurements using an open field activity monitoring system for skeletal muscle diseases.” Journal of visualized experiments: JoVE 91 (2014).
5. Zhang, Jian-Jun, and Qingyao Kong. “Locomotor activity: A distinctive index in morphine self-administration in rats.” PloS one 12.4 (2017): e0174272.
6. Alkam, Tursun, and Toshitaka Nabeshima. “Modeling the Positive Symptoms of Schizophrenia.” Handbook of Behavioral Neuroscience. Vol. 23. Elsevier, 2016. 39-54.
7. De Santis, Michael, et al. “Early antipsychotic treatment in childhood/adolescent period has long-term effects on depressive-like, anxiety-like and locomotor behaviours in adult rats.” Journal of Psychopharmacology 30.2 (2016): 204-214.
8. Erta, Maria, et al. “Astrocytic IL-6 mediates locomotor activity, exploration, anxiety, learning and social behavior.” Hormones and behavior 73 (2015): 64-74.
9. Mugikura, Shin-ichiro, et al. “Abnormal gait, reduced locomotor activity and impaired motor coordination in Dgcr2-deficient mice.” Biochemistry and biophysics reports 5 (2016): 120-126.