NIH Research Festival
Dopamine neurons play roles in many behaviors and diseases, from reward learning to addiction. The release of dopamine from terminals has been studied for decades using methods like voltammetry, microdialysis, and calcium imaging. However, these indirect methods severely limit experimental access to questions regarding the influence of subthreshold conductances on dopamine release from axon terminals. To study the influence of subthreshold conductances on axonal excitability, we developed methods to obtain whole-cell patch clamp recordings directly from the cuts ends of dopamine cell axons in cells that maintained an intact connection to the soma. Here we demonstrate the presence of GABA-A receptors on the axons of dopaminergic neurons recorded in adult mice. Unlike in the soma where GABA-A receptors are typically hyperpolarizing, however, we found that activation of axon GABA-A receptors leads to depolarization. Furthermore, GABA-A receptor activation in the axon decreases action potential amplitude, but does not affect the firing rate when the receptors are transiently activated. Currently, we are conducting experiments to establish how GABA-A receptor activation on the axon may modify dopamine release at the terminals. Among the possibilities, depolarizing axonal GABA-A receptors may inhibit synaptic release through either shunting inhibition or through depolarization-induced sodium channel inactivation. Alternatively, GABA-A receptors may enhance neurotransmitter release through an increase in calcium entry. Therefore, these experiments will test the idea that axonal GABA-A receptors on dopamine neuron axons represent a novel element in the circuit control of striatal dopamine release.
Scientific Focus Area: Neuroscience
This page was last updated on Friday, March 26, 2021