Schizophrenia is a complex mental disorder characterized by abnormalities in the perception or expression of reality. Naturally, gene-modified mice could only model some aspects of the psychopathology. Only a few behavioural tests are relevant measures of schizophrenia-related behaviour in mice such as: prepulse inhibition, latent inhibition, working memory and hyperactivity.

Latent Inhibition (LI) refers to the proactive interference of non-reinforced stimulus pre-exposure with the capacity to downgrade the behavioural control of stimuli that predict no significant consequences. In other words, LI measures the organism's ability to ignore irrelevant stimulus, which is decremental form of attention. LI is disrupted in rodents and humans treated with amphetamine and acute stage of schizophrenia. Working memory could be assessed by different means, and we offer the T-maze for this purpose (see Cognition).


Latent Inhibition



Before the beginning of each LI experiment, mice are weighed and water is removed from the cages for 24 hours. They are then trained to drink in the experimental chamber for 5 days, 15 minutes per day (training period). Body weights are monitored daily throughout all behavioural testing and maintained at no lower than 80% of the initial body weight. On each daily training session, mice are acclimated to the chamber without access to the sipper tube for 5 minutes then the guillotine door is opened. Latency to the first lick and number of licks are recorded for 15 minutes. The LI procedure is conducted on days 6-9 and consisted of the following stages:
Pre-exposure. The pre-exposed (PE) mice receive 40 white noise presentations with an interstimulus interval of 60 seconds. The non-pre-exposed (NPE) mice are confined to the chamber for an identical period of time without receiving the stimuli.
Conditioning. All mice receive fear conditioning to the noise stimulus. To estimate baseline performance 2 noise-shock pairings are used and 4 noise-shock pairings are used to disrupt LI in order to estimate ability of drug (or gene) to facilitate LI. 5 minutes after the start of the session, a 10 second white noise is followed by a 1 second 0.37mA foot shock. The noise-shock pairings are given 5 minutes apart. After the last pairing, mice are left in the experimental chamber for an additional 5 minutes. Mice receive access to water in their home cages for 15 minutes after pre-exposure and conditioning sessions. Lick retraining. Mice are given a 15 minute drinking session as during the training period. Data of mice that failed to complete 100 licks are dropped from the analysis.
Test. Each mouse is placed in the chamber with access to the sipper tube.
When the mouse complete 75 licks the noise is presented and lasted until the mouse reached lick 101. The following times are recorded: Time to first lick, time to complete licks 50-75 (before noise onset; A period), and time to complete licks 76-101 (after noise onset; B period). Degree of lick suppression is calculated as a suppression ratio A/(A + B). A lower suppression score indicates a stronger suppression of drinking. LI consists of lower suppression of drinking (higher suppression ratio) in the pre-exposed compared to the non-pre-exposed mice.



Figure 1. Latent Inhibition