The Correlation Between Cage Stereotypies and Basal Ganglia Dysfunction

Katie Harrell

Dr. Whittaker

AGR 101H

23 September 2006

The Correlation Between Cage Stereotypies and Basal Ganglia Dysfunction

1. Introduction and Problem Statement

Since the first mouse was used in a lab, scientists have been curious why laboratory animals exhibit stereotypies. Stereotypies are the repeated, seemingly useless, motor behaviors many animals in captivity display. Although researchers could define the causation of a certain cage stereotypy on a physical level more fundamental, neurophysiological understanding of the disorder remained unknown. For example, scientists know that animals caught in the wild as adults do not exhibit stereotypies, but lab raised animals of the same species do. It's also known that isolation-rearing and premature weaning induce stereotypy and basal ganglia changes. Doctors J.P. Garner and G.J. Mason believed a relationship might be present between the stereotypies shown by these animals and those displayed by humans with altered mental functions.

2. Hypothesis

Since human psychological disorders have been studied more thoroughly than those in animals there is prevalent information for Doctors Garner and Mason to base their supposition upon. In individuals affected by schizophrenia and autism the part of the brain known as the basal ganglia causes repetition of words and disorganized movement. Amphetamine abusers are known to have motor problems stemming from the disintegration of their basal ganglia also.

It seems in most of these individuals the negative feedback of the basal ganglia, that is, the impulse that tells the brain that a task has been complete, is inhibited. This explains why affected individuals have repetitive, sometimes rhythmic behaviors for no reason or why motor movements continue well after a task is complete. The person simply cannot stop themselves because the message essentially misfires. Knowing all of this Garner and Mason designed experiments intended to prove that cage stereotypies are directly related to the basal ganglia.

2. Materials and Methods

Using eight lab bred bank voles the researchers began their first experiment which involved very little. The voles were weaned and immediately placed into separate, opaque cages. All voles were kept on a 14 hour light-10 our dark cycle and monitored on video. In the videos all of the voles practiced the "bar-mouthing" stereotypy in the 4 hours of active behavior. "Bar-mouthing" is a process in which the animal holds the cage bar in the gap between the prominent front teeth and the molars and makes fake biting movements along the bar. Each of the voles performed this "bar-mouthing" individually in relation to time and location on the cage.

Another part of this observation period was to determine the rate of behavior initiation. In stereotypies related to amphetamine stereotypy occurs after competing behavioral responses can no longer be switched on and off and a single, predominant behavior is continuously repeated. To look at rates of behavior initiation four periods of uninterrupted activity each lasting four minutes were randomly chosen from the eight hours of video recorded. To make sure all the animals were analyzed equally two of the four time intervals selected were during stereotypy performance and the other two when it was not.

The sixteen minutes of recording were viewed continuously and each time a behavior was initiated it was recorded. For example, nest building-eating-grooming-eating-drinking has four initiations, one between each or the individual behaviors. After the number was recorded the mean number of behaviors initiated per minute was calculated and compared with stereotypy. The results were biased for each sex.

The next test involved using mazes to measure the general tendency to repeat previous responses even when they are known to be incorrect. This is known as recurrent perseveration. These tendencies stem from damage to the basal ganglia and, as mentioned, are also present in schizophrenics and autistics.

The tests used mazes of clear plastic tube and were mounted to the home cage. Computers collected all data, automatically ran tests and dispensed rewards so human researchers did not affect the voles. Subjects entered the maze and chose a corridor to venture down, both of which supplied a reward of sucrose solution and exited to the home cage. Then, in the spatial discrimination test only one corridor was supplied with the reward. Lastly, neither corridor offered a reward.

The ability of the voles to make new decisions after developing a pattern in the first trials was used to investigate the knowledge-action dissociation. The theory behind this is called extinction. In extinction, knowledge of the task is shown as choices return to chance and as the latency to choose previously correct corridors matches that of the previously incorrect side. Based on graphs presented in Garner and Mason's paper, the most stereotypic voles were able to choose the