The circling ci2 rat mutant revisited: receptor architecture of the motor cortex

Abstract

Circling behaviour of the ci2 rat mutant has been associated with an abnormal laterality concerning nigrostriatal and vestibular dopamine content and densities of several neurotransmitter receptors. Since not only subcortical, but also cortical activity subserve behavioural asymmetry, we applied quantitative in vitro receptor autoradiography to determine the densities of twenty neurotransmitter receptors in three areas of the motor cortex (Fr1, Fr2, Fr3) of the left and right hemispheres in adult male circling mutant rats (ci2/ci2), non-circling littermates (ci2/+) and aged-matched rats from the background strain (LEW/Ztm, wild type). Rats had previously been monitored for motor behaviour and swimming abilities. Wild type and ci2/+ rats did not differ from the behavioural point of view, whereas ci2/ci2 animals were characterized by pronounced lateralized circling behaviour and were not able to perform the swimming test correctly. Left Fr2 of wild type rats contained significantly lower NMDA receptor densities than its right counterpart. No interhemispheric differences were found in the motor cortex of ci2/+ or ci2/ci2 animals. All three areas of wild type rats contain higher GABAA and adenosine A1 receptor densities than those of ci2/+ and ci2/ci2 animals, respectively. Serotonin 5-HT2 receptor densities were significantly lower in the motor cortex of ci2/ci2 animals than in that of their heterozygous littermates. Thus, since the ci2 rat mutant presents a wide range of behavioural and neurochemical lateralization anomalies, in addition to representing a model of Usher syndrome type 1, it may prove useful to understand the mechanisms underlying abnormal rotational behaviour and its relevance as a model of disturbances in cerebral asymmetry and their consequences.