The automated hole-board COGITAT detects long-term effects after cerebral oligaemia and intracerebral iron

C. Heim1, W. Kolasiewicz2, M. Sieklucka3, T. Sontag4, I. Pardowitz5 and K.H. Sontag1

1Max Planck Institute for Experimental Medicine, Göttingen, Germany
2Institue of.Pharmacology, Krakow, Poland
3Institute for Hygiene, Lublin University Medical School, Poland
4Nijmegen Institute of Neuroscience, University of Nijmegen, Nijmegen, The Netherlands
5Cognitron GmbH, Göttingen, Germany

In order to follow the development of event-related deficiencies, whose appearance may be delayed or may be progressive, and in order to gain an accurate impression of the time course of such abnormal behaviour patterns as may arise, it is necessary, at various times to follow many different behavioural parameters simultaneously under c omparable conditions.

Features thought to be associated with neurodegenerative diseases include oligaemic episodes and increased iron concentrations in discrete brain regions. Therefore, male Wistar rats which had a 60 min oligaemic episode (bilateral clamping of carotid arteries: BCCA) or sham-operation were injected one week later with FeCl3 either intranigrally (35ng/0.25µl, bilaterally) or intrastriatally (1.5µg/2µl, unilaterally), or the same volume of buffer.

The mechanical opto-electronic system COGITAT (Cognitron GmbH, Göttingen, Germany) was developed for the simultaneous measurement of spatial learning, working and reference memory, overall exploratory activity, visits deep in the holes of a hole-board as well as perfunctory inspections of the holes, and the sequential collection of hidden food pellets, as well as re-learning after different time intervals, and the shifting capability, together with their statistical and graphic presentation. The board, with 25 deep holes, is framed by transparent walls and has a special entrance with a starting box where the rats adapt for 10 s before entering the board. Eight of the holes are serially baited with small (40 mg) food pellets distributed in a distinct pattern not visible to the animals while walking. The animals are tested in a random manner, and learn the pattern during exploration, using their individual strategies. A trial on the board ends as soon as the animal has found and eaten all of the 8 pellets or after a predetermined time, whichever is sooner. Care has to be taken that subsequently the animals are always handled by the same experimenter, and experience the identical environment including identical intra-maze and external cues, and that they are tested at the same time of day, taking the yearly summer and winter clock changes into consideration. Starting one week prior to the test period, and throughout the entire experimental session, the animals have to be put on starvation rations (12-15 g of laboratory chow), so their weight falls to only ~90% of normal [1]. On experimental days, animals have to be adapted to the experimental room for 1 h before the start of the experiment, remaining in their home cages, and during this time receiving their whole daily food ration before the experiment begins. After having learnt to find all the hidden pellets distributed in a pattern "A" mainly in the centre of the board over 10 3-min sessions (1/day), over 8 1-min sessions, and finally 13 30-s sessions three months after surgery, the animals were then immediately confronted with pellets hidden in a new pattern "B", adjacent to the board enclosure [1]. After 6, 9, 12 and 15 months after surgery (for striatally injected rats), or 7, 12, 15, and 18 months (for nigrally injected rats), the patterns were offered to each animal in an alternating sequence: pattern A on five successive days, followed the next week by pattern B on five successive days, followed by pattern A again the next week, and vice versa, i.e. after a break of about three months starting with that pattern that had not been presented at the last experimental session previously.

Intracebrally increased iron, alone or after BCCA, leads to alterations in the hole-board performance. This however depends on which side the iron was injected. While the effects of unilateral striatal iron amounts seem to be made worse by an oligaemic episode, one week beforehand, a previous BCCA episode appears to ameliorate the adverse effects of the bilateral administration of minuscule intranigral iron deposits. Remnant subtle deficits seem to get corrected through an altered learning strategy. The COGITAT system provides data that enable one to recognise specific deficiencies in different pathological situations by analysing the complete range of at least 25 different behavioural parameters and can thus provide an objective characterisation of any system being analysed.

References

  1. Heim, C.; Pardowitz, I.; Sieklucka, M.; Kolasiewicz, W.; Sontag, T.; Sontag, K.H. (2000). The analysis system COGITAT for the study of cognitive deficiencies in rodents. Behavior Research Methods, Instruments & Computers, 32, 140-156.

Poster presented at Measuring Behavior 2000, 3rd International Conference on Methods and Techniques in Behavioral Research, 15-18 August 2000, Nijmegen, The Netherlands

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