Activation of glycine receptors decreases pacemaking activity in midbrain dopamine neurons independent of the alpha 2 subunit

Abstract

Dopamine is a neurotransmitter of the brain and tight modulation of its release is essential for a proper brain function. Dysfunction of dopamine signaling is associated with various diseases, such as Parkinson's disease and psychosis. The activity of dopamine releasing neurons is modulated in the midbrain and elucidating these modulatory mechanisms is essential for unveiling the etiology of these diseases and development of new treatment strategies. The neurotransmitter glycine plays a major role in the modulation of dopamine neuron activity, yet it is unclear which subunits are involved. To address this gap, we first confirmed the inhibitory effect of glycine on basal dopamine neuron firing in the substantia nigra pars compacta (SNc) within the midbrain. Next, since preliminary data from our lab indicate a significant role for the alpha 2 subunit of the glycine receptor (GlyR'2) in dopaminergic signaling, we checked the presence of the subunit on dopamine neurons and repeated the firing experiments in GlyR'2 knock-out littermates to determine its functional role. Our findings clearly demonstrate the involvement of glycine receptors in modulation of dopamine neuron activity, but modulation was independent of GlyR'2s at baseline activity and activity in presence of synaptic glycine concentrations. However, it is conceivable that high-affinity GlyR'2s are involved in the modulation at lower, tonic glycine concentrations and/or in phasic activity.