Lesions of the lateral habenula improve working memory performance in hemiparkinsonian rats

The lateral habenula (LHb) is an important structure involved in various brain functions, because it controls the activity of dopaminergic and serotonergic systems in the midbrain. The impairment of working memory commonly occurs in Parkinson's disease; however, it is not clear whether the LHb involves in the regulation of working memory in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle (MFB). In this study, we found that the MFB lesions in rats decreased choice accuracy as measured by the T-maze rewarded alternation test compared to control rats, indicating the induction of working memory impairment, and decreased dopamine (DA) levels in the medial prefrontal cortex (mPFC), hippocampus and amygdala. Further, rats in the MFB and LHb lesion group showed increased choice accuracy compared to rats in the MFB lesion group, indicating the enhancement of working memory after lesioning the LHb. Neurochemical results found that lesions of the LHb increased DA levels in the mPFC, hippocampus and amygdala in the MFB and LHb lesion group, as well as serotonin (5-HT) level in the mPFC. These findings suggest that DA depletion plays a key role in working memory impairment, and lesions of the LHb improve working memory in the MFB-lesioned rats, which involves in increases in the levels of DA and 5-HT in the mPFC, hippocampus and amygdala. Additionally, the present results may have implications for improving our understanding of the neuropathology and/or treatment of PD.