Wheel Running and Environmental Complexity as a Therapeutic Intervention in an Animal Model of FASD

The overall goal of this behavioral intervention is to enhance environmental stimulation of laboratory rodents via exposure to voluntary cardiovascular exercise and environmental complexity in a controlled laboratory setting. This technique can help answer key questions in the field of rehabilitation and neuroplasticity. It highlights the importance of social exercise and exploratory behaviors on neurological development in adolescence and health maintenance in adulthood.

The main advantage of this procedure is that it combines the exercise and environmental complexity in a synergistic way, and it allows the interpretation of each of the components separately if need be. To begin the experiment, place weaned rat pups into an appropriate cage and make sure that they always have free access to food and water. A week later, on day 30 of their development, move half the rats into exercise cages with running wheels.

Each running wheel should have a revolution counter and be freely accessible. On the same day, weigh all the rats. Every following day at the same hour, check the number of revolutions on the running wheels.

On day 36, weigh the rats again. Then, leave them in their respective housing condition for 12 days until day 42. Early on developmental day 42, prepare the environmentally complex cages.

The 30 by 18 by 36 inch galvanized steel cages should contain multiple levels capable of supporting the weight of multiple rats. These cages must also be capable of supporting standard bedding and multiple food and water dispensers. Place novel colorful objects of variable sizes and shapes in the cage.

First, position six large toys in the cage that are large enough for three or more rats to interact with concurrently. Next, place six medium-sized toys in the cage each of which should also be large enough for three or more rats to use concurrently. Then, place at least 20 small toys in the cage that might only occupy one rat at a time.

Select toys of different colors and shapes to enhance the complexity. The novelty of each toy is critical to this form of intervention. At the opposite ends of the cage, place food dispensers and attach water bottles so each cage has two of each.

Once the cages are prepared, weigh all the animals and relocate them to the environmentally complex cages. Group nine to 12 animals per cage, making certain that they all have unique identifiers. Every two days, replace all the toys.

Make sure to have enough toys such that animals rarely encounter the same toy twice during the paradigm. When replacing the toys, also refill the food and water. Every third day, clean the cages.

Temporarily house the rats in groups of two or three and replace the bedding, food, and water. Return the same toys to the cage on these days unless cleaning coincides with the toy replacement schedule. The wheel running and complex environmental interventions impacted adult neurogenesis in the dentate gyrus as assessed by BrdU staining.

Increases in cell proliferation were observed following the wheel running portion of the intervention in the normally developing early life stressed and alcohol-exposed animals. The complex environment intervention increased the survival of adult-generated cells in the dentate gyrus in animals that were exposed to either stress or alcohol neonatally. Furthermore, the interventions resulted in an increase in cells that differentiate into a neuronal phenotype as seen with increases in adult-born dentate gyrus granule cells despite neonatal exposure to alcohol or intubation stress.

Investigating the length of double cort and positive dentrites of dentate gyrus granule cells showed that there was no difference between the alcohol-exposed rats and control rats after wheel running and environmental complexity intervention. After watching this video, you should have a really good understanding of how to appropriately lay out the environmental complexity cage as well as how to house animals in the wheel running cages and environmental complexity cages. When attempting this procedure, it's important to thoroughly clean all of your materials and check up on your animals daily.

Following this procedure, the behavioral, neurophysiological, and neuroanatomical measures can be assessed in order to determine the consequences of exposure to wheel running and environmental complexity interventions. After its development, this technique paved the way for researchers in the field of neuroplasticity to explore experience-dependent changes in rodent models of neurological disease.