TY - JOUR
T1 - High frequency stimulation of the subthalamic nucleus increases c-fos immunoreactivity in the dorsal raphe nucleus and afferent brain regions
AU - Tan, Sonny K. H.
AU - Janssen, Marcus L. F.
AU - Jahanshahi, Ali
AU - Chouliaras, Leonidas
AU - Visser-Vandewalle, Veerle
AU - Lim, Lee Wei
AU - Steinbusch, Harry W. M.
AU - Sharp, Trevor
AU - Temel, Yasin
PY - 2011/10
Y1 - 2011/10
N2 - High frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced Parkinson's disease, but this treatment can elicit disabling mood changes. Our recent experiments show that in rats, HFS of the STN both inhibits the firing of 5-HT (5-hydroxytryptamine; serotonin) neurons in the dorsal raphe nucleus (DRN) and elicits 5-HT-dependent behavioral effects. The neural circuitry underpinning these effects is unknown. Here we investigated in the dopamine-denervated rat the effect of bilateral HFS of the STN on markers of neuronal activity in the DRN as well as DRN input regions. Controls were sham-stimulated rats. HFS of the STN elicited changes in two 5-HT-sensitive behavioral tests. Specifically, HFS increased immobility in the forced swim test and increased interaction in a social interaction task. HFS of the STN at the same stimulation parameters, increased c-fos immunoreactivity in the DRN, and decreased cytochrome C oxidase activity in this region. The increase in c-fos immunoreactivity occurred in DRN neurons immunopositive for the GABA marker parvalbumin. HFS of the STN also increased the number of c-fos immunoreactive cells in the lateral habenula nucleus, medial prefrontal cortex but not significantly in the substantia nigra. Collectively, these findings support a role for circuitry involving DRN GABA neurons, as well as DRN afferents from the lateral habenula nucleus and medial prefrontal cortex, in the mood effects of HFS of the STN.
AB - High frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced Parkinson's disease, but this treatment can elicit disabling mood changes. Our recent experiments show that in rats, HFS of the STN both inhibits the firing of 5-HT (5-hydroxytryptamine; serotonin) neurons in the dorsal raphe nucleus (DRN) and elicits 5-HT-dependent behavioral effects. The neural circuitry underpinning these effects is unknown. Here we investigated in the dopamine-denervated rat the effect of bilateral HFS of the STN on markers of neuronal activity in the DRN as well as DRN input regions. Controls were sham-stimulated rats. HFS of the STN elicited changes in two 5-HT-sensitive behavioral tests. Specifically, HFS increased immobility in the forced swim test and increased interaction in a social interaction task. HFS of the STN at the same stimulation parameters, increased c-fos immunoreactivity in the DRN, and decreased cytochrome C oxidase activity in this region. The increase in c-fos immunoreactivity occurred in DRN neurons immunopositive for the GABA marker parvalbumin. HFS of the STN also increased the number of c-fos immunoreactive cells in the lateral habenula nucleus, medial prefrontal cortex but not significantly in the substantia nigra. Collectively, these findings support a role for circuitry involving DRN GABA neurons, as well as DRN afferents from the lateral habenula nucleus and medial prefrontal cortex, in the mood effects of HFS of the STN.
KW - Subthalamic nucleus
KW - High frequency stimulation
KW - Parkinson's disease
KW - Depression
KW - Serotonin (5-HT, 5-Hydroxytryptamine)
KW - Dorsal raphe nucleus
U2 - 10.1016/j.jpsychires.2011.04.011
DO - 10.1016/j.jpsychires.2011.04.011
M3 - Article
C2 - 21641003
SN - 0022-3956
VL - 45
SP - 1307
EP - 1315
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
IS - 10
ER -