Asymmetrical Fos Expression in the Unilateral 6-OHDA Model in Rats

Recently, Bassett and Taube (2001) have identified asymmetric angular head velocity (AHV) cells, which fire in response to head rotations in one direction, in the dorsal tegmental nucleus of Gudden (DTN). These asymmetric AHV cells tend to be located in the DTN contralateral to their turn preference (Bassett & Taube, 2001). More recently, we have identified asymmetric Fos expression in the DTN following unilateral rotation. Following drug-induced rotation or operant-conditioned rotation, rats expressed more Fos in the DTN contralateral to the direction of rotation. We hypothesized that asymmetric Fos expression in the DTN represented the persistent activity of asymmetric AHV cells in response to sustained rotational behavior. Here, we investigated the behavioral and neural substrates contributing to DTN Fos expression. In the first experiment, animals with a unilateral 6-hydroxydopamine (6-OHDA) lesion were treated with amphetamine, and then half of the animals were allowed to rotate in automated rotometers, while the other half were restrained to prevent rotation. Restraint abolished asymmetric Fos expression in the DTN. In the second experiment, the role of the lateral habenula in DTN Fos expression was investigated. Bilateral electrolytic habenula lesions (or sham lesions) were produced along with unilateral 6-OHDA lesions, and Fos expression was examined following rotation. Habenula lesions failed to abolish asymmetric Fos expression in the DTN but did produce an overall reduction in DTN Fos. Lastly, we employed double-labeling fluorescent techniques to confirm that the DTN cells that project to the lateral mammillary nucleus were the same cells that expressed Fos following rotation. Additionally, we used these methods to investigate other neural substrates, (i.e., the supragenual nucleus (SGN) and the nucleus prepositus hypoglossi (PrH)) that may play a role in the activity in the DTN. We found asymmetric Fos expression in these areas with greater Fos expression in the contralateral PrH and the ipsilateral SGN, perfectly mimicking the known anatomical projections from these areas to the DTN. The implications of these results and future experiments are discussed. Taken together, these results suggest that these areas form a functional circuit contributing to the encoding of AHV, and more generally, spatial information.