Data from: Dopamine and serotonin co-transmission filters striatonigral synaptic activity via 5-HT1B receptor activation

The substantia nigra pars reticulata (SNr), a key basal ganglia output
nucleus, is modulated by dopamine (DA), believed to be released locally
from midbrain dopamine neurons. Although DA has been proposed to regulate
GABA release from medium spiny neurons (MSN) terminals via presynaptic D1
receptors (D1Rs), the precise mechanisms remain unclear. Using presynaptic
optical recordings of synaptic vesicle fusion, calcium influx in D1-MSN
synapses, together with postsynaptic patch-clamp recordings from SNr
neurons, we found that DA inhibits D1-MSN GABA release in a
frequency-dependent manner. Surprisingly, this effect was independent of
DA receptors and instead required 5-HT1B receptor activation. Using
two-photon serotonin biosensor imaging in slices and fiber photometry in
vivo, we demonstrate that DA enhances extracellular serotonin in the SNr.
Our results suggest that serotonin mediates DAergic control of basal
ganglia output and contributes to the therapeutic actions of dopaminergic
medications for Parkinson’s disease and psychostimulant-related disorders.