Control Experiments

A. Open Field Analysis and Elevated Plus Maze Performance

Open field analysis is used to measure the level of spontaneous motor activity, exploratory behavior, and habituation of animals to an open area. Animals are placed in an open field chamber (e.g., 40 by 40 by 30 cm box) for 15 minutes in standard room-lighting conditions. Activity in the open field is typically monitored by light beams and photoreceptors on each side of the chamber and analyzed by a computer-operated optical animal activity system. With this test, general activity levels are evaluated by measuring of horizontal activity, vertical activity, and total distance traveled during a 10-minute test session in an open box in a lighted room (see Figure 16). These types of data are used to screen for hyperactivity, which can be a complication to the assessment of many different types of learned behaviors. The open field test also can be used to measure anxiety levels, as assessed by the center distance to total distance ratio. In the more general literature, this assessment is often used in conjunction with the Elevated Plus Maze as an anxiety index.

B. Rotating-Rod Performance— Coordination and Motor Learning

The rotating rod task is commonly used to assess two parameters related to cerebellar function. Initial trials are used to assess the animal's coordination. The amount of time an animal can stay on a rotating rod is an index of its general level of coordination. Obviously, motor coordi-ation is an important component of most behavioral assessments of learning where complicated motor output is necessary for successful execution of a learned task. Mice

FIGURE 16 Open field behavior. Animals were placed in the open field apparatus, and their activity was monitored using automated recording equipment. (A) Total distance traveled per minute for a 10-minute period. (B) Vertical activity (number of rearings per minute) over a 10-minute period. (C) Ratio of center distance to total distance traveled for each minute over a 10-minute period. The data in panels A and B are taken as indices of general activity; the data in panel C are taken as an index of anxiety. Results shown are for C57Bl6 animals, mean ± SEM for n = 10. Data courtesy of Coleen Atkins (10).

FIGURE 16 Open field behavior. Animals were placed in the open field apparatus, and their activity was monitored using automated recording equipment. (A) Total distance traveled per minute for a 10-minute period. (B) Vertical activity (number of rearings per minute) over a 10-minute period. (C) Ratio of center distance to total distance traveled for each minute over a 10-minute period. The data in panels A and B are taken as indices of general activity; the data in panel C are taken as an index of anxiety. Results shown are for C57Bl6 animals, mean ± SEM for n = 10. Data courtesy of Coleen Atkins (10).

FIGURE 17 Rotating rod behavior. Total time the animals remained on the rotating rod was measured for each training period. Three training trials were given in a single day. The increase in time the animal remained on the rod is taken as an index of motor learning. Results shown are for C57Bl6 animals, mean ± SEM for n = 10 animals. Data courtesy of Coleen Atkins (10).

FIGURE 17 Rotating rod behavior. Total time the animals remained on the rotating rod was measured for each training period. Three training trials were given in a single day. The increase in time the animal remained on the rod is taken as an index of motor learning. Results shown are for C57Bl6 animals, mean ± SEM for n = 10 animals. Data courtesy of Coleen Atkins (10).

and rats also improve their performance with training (see Figure 17), which is an indicator of motor learning. Thus, motor skill acquisition can be assessed in its own right by determining the rate of improvement on the task upon repeated trials.

C. Acoustic Startle and Pre-Pulse Inhibition

Just like humans, mice and rats normally exhibit a startle response to a loud noise. Interestingly, if a modest noise is presented immediately preceding the loud noise, the startle response is significantly attenuated (see Figure 18) in all three species. This phenomenon is referred to as pre-pulse inhibition. In rats and mice pre-pulse inhibition can be used to assess the animal's general reflexes (startle), and it also serves as a very sensitive and quantitative assessment of the animal's hearing. Normal mice, for example, exhibit pre-pulse inhibition with a threshold around 70 dB, and reliably give quantitatively different responses to pre-pulses varying by only a few decibles (see Figure 18). Of course, hearing assessment is a critical control for cued fear condi-ioning, and pre-pulse inhibition can be used in this fashion. Pre-pulse inhibition is also used as an assessment of sensory-motor gating, which is deranged in schizophrenic patients. Thus, pre-pulse inhibition in rodents can also be used to model this aspect of schizophrenia.

D. Nociception

In many behavioral training paradigms, aversive sensory stimuli are utilized. It is important to note that it is almost universally the case that modest aversive stimuli are much more effective for training animals than are painful stimuli. In this

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