Increased excitability in serotonin neurons in the dorsal raphe nucleus in the 6-OHDA mouse model of Parkinson's disease

- 6-OHDA lesion increases spontaneous firing of dorsal raphe nucleus serotonin neurons.
- 6-OHDA lesion increases maximal firing of dorsal raphe nucleus serotonin neurons.
- l-DOPA does not reverse the increase in spontaneous firing.
- 6-OHDA lesion decreases the duration of action potential, while l-DOPA reverses it.

The serotonin system has recently been demonstrated to have an important role in Parkinson's disease, in particular in response to l-DOPA treatment. It has been shown that central serotonin neurons convert peripherally administered l-DOPA to dopamine. Striatal dopamine release by these serotonin neurons is believed to be a main player in the induction of the troublesome l-DOPA-induced dyskinesias, which develops in patients within 5-10 years after the use of the drug. Electrophysiological characterization of midbrain dopamine neurons and dorsal raphe nucleus serotonin neurons has further revealed close interaction between these two cells groups. These data indicate that the loss of dopamine neurons and fibers alone and following l-DOPA treatment might change the electrophysiological properties of the serotonin neurons in the dorsal raphe nucleus. Although in vivo data have indicated changes in firing properties following dopamine depletion by 6-OHDA, the data have been conflicting. We therefore investigated the electrophysiological properties of serotonin neurons following dopamine degeneration and l-DOPA treatment in the 6-OHDA-lesion mouse model of Parkinson's disease using in vitro patch clamp technique in acute slices. We found that 6-OHDA lesions alone significantly increased spontaneous and maximal firing discharges of serotonin neurons, which were accompanied by respective changes in the action potential waveforms. l-DOPA treatment did not reverse this increase in spontaneous frequency, but partially normalized AP properties. Our data demonstrate that the intrinsic excitability of serotonin neurons is altered in response to both dopamine degeneration as well as subsequent l-DOPA treatment. This lesion- and treatment-induced plasticity of the serotonin might contribute to its role in l-DOPA induced dyskinesia.