Serotonergic (5-HT) neurons degenerate in Parkinson's disease. To determine the role of this 5-HT injury-besides the dopaminergic one in the parkinsonian symptomatology-we developed a new monkey model exhibiting a double dopaminergic/serotonergic lesion by sequentially using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3,4-methylenedioxy-N-methamphetamine (MDMA, better known as ecstasy). By positron emission tomography imaging and immunohistochemistry, we demonstrated that MDMA injured 5-HT nerve terminals in the brain of MPTP monkeys. Unexpectedly, this injury had no impact on tremor or on bradykinesia, but altered rigidity. It abolished the l-DOPA-induced dyskinesia and neuropsychiatric-like behaviours, without altering the anti-parkinsonian response. These data demonstrate that 5-HT fibres play a critical role in the expression of both motor and non-motor symptoms in Parkinson's disease, and highlight that an imbalance between the 5-HT and dopaminergic innervating systems is involved in specific basal ganglia territories for different symptoms.

SummarySporulation in Bacillus subtilis is a primitive differentiation process involving two cell types, the forespore and the mother cell. Each cell implements two successive transcription programmes controlled by specific sigma factors. We report that activity of s G , the late forespore sigma factor, is kept in check by Gin, the product of csfB, a gene controlled by s F , the early forespore sigma factor. Gin abolishes s G transcriptional activity when s G is artificially synthesized during growth, but has no effect on s F . Gin interacts strongly with s G but not with s F in a yeast two-hybrid experiment. The absence of Gin allows s G to be active during sporulation independently of the mother-cell development to which it is normally coupled. Premature s G activity leads to the formation of slowgerminating spores, and complete deregulation of s G synthesis is lethal when combined with gin inactivation. Gin allows s F to delay the switch to the late forespore transcription programme by preventing s G to take over before the cell has reached a critical stage of development. A similar strategy, following a completely unrelated route, is used by the mother cell.