Neurological Disorders: Trace Conditioning
Cognition, especially the loss of cognitive abilities in dementias such as Alzheimer's disease, later-stage Parkinson's disease, and Huntington's disease, as well as in schizophrenia, is a major focus of research. This area has been hampered particularly by the lack of rapid assays that specifically target the learning and memory losses associated with these diseases, i.e. learning and memory dependent on areas of the brain such as the hippocampus. Assays generally used, such as the eight-arm radial arm maze or delayed non-matching-to-sample procedures require significant time and training. However, animals learn aversive conditioning very easily and it has been found that this can be combined with ‘trace’ conditioning, in which there is a time interval between the signal stimulus and the aversive stimulus itself, to provide a rapidly (3-5 trials) learned response that is dependent upon the function of the hippocampus. This assay has been automated to increase objectivity and make it appropriate for high throughput behavioral analysis. Pharmacological validation of this test has been performed. Impairment of contextual and auditory-cue fear conditioning has been observed after administration of the muscarinic receptor antagonist scopolamine (Rudy et al., 1996).
Groups of naive mice are trained in conditioning chambers that have stainless steel rod floors through which foot shocks are delivered. For cued trace fear conditioning mice are placed in training context and left undisturbed for habituation purposes for 3 minutes. Then a conditioned stimulus (CS: 15 second duration, 85 dB 3kHz) generated by tone is delivered, followed by a trace period of 10 sec and the unconditioned stimulus (US: footshock, 2 sec, 0.35 mA). Mice are presented with 3 trials with inter-trial interval (ITI) 2 min and returned to the home cage 1 minute after the final shock. As an animal learns to associate the US with the CS, freezing responses to the CS increases over trials.
Displayed below is a sample graph of how trace conditioning observations are presented. In comprehensive phenotypic data packages graphs are interactive. Raw or calculated data and statistics can be seen by clicking on points in the graph.
Figure represents change in percentage freezing during trace conditioning trials of male and female (left), male (center), and female (right) mutant mice. Percent freezing for wild type littermates (green circle), homozygous (red diamond), and recent historical wild types (purple line) are plotted against long-term historical percentage freezing values (± 2 standard deviations) for wild type animals (green shading). Recent wild type values are calculated from data collected within 60 days of current measures and long-term historical values are derived from data collected on more than 10,000 wild type mice.
Rudy JW. (1996) Scopolamine administered before and after training impairs both contextual and auditory-cue fear conditioning, Neurobiol Learn Mem, 65(1):73-81.