Ünal, Bengi. Tyrosine hydroxylase-expressing interneurons in intact and dopamine-depleted striatum. Retrieved from https://doi.org/doi:10.7282/T34748MN
DescriptionTyrosine hydroxylase-expressing (TH+) interneurons of the striatum stand in a critical point for our understanding of the interaction between striatal dopamine and striatal interneurons. Recent investigations from our laboratory have established that TH+ neurons comprise an electrophysiologically distinct group striatal GABAergic interneurons by using transgenic mice expressing enhanced green fluorescent protein under the control TH promoter (TH-eGFP). In order to understand the significance of striatal TH+ neurons in the normal and dopamine-depleted striatum, determining anatomical distribution of TH+ neurons with regard to their electrophysiological diversity and striatal anatomical heterogeneity was imperative. In the first part of my thesis, I investigated striatal localization of TH-eGFP neurons with respect to anatomical organization of the striatum. In the second set of experiments, I investigated the changes in anatomical distribution, morphology, and electrophysiology of TH-eGFP neurons following striatal dopamine-depletion. Data presented here indicates that the electrophysiological subtypes of TH-eGFP interneurons are equally prevalent throughout striatum. However, when patch/striosome-matrix organization is taken into account, a different pattern emerges in the dorso-ventral axis of the striatum: a significantly higher proportion of striatal TH-eGFP interneurons were located in MOR-enriched domains of the ventral striatum. Finally, TH-eGFP interneurons in both compartments extended their neurites into the neighboring compartment. In the second set of experiments, I investigated the effect of striatal dopamine loss achieved by unilateral intranigral 6-OHDA infusion on TH-eGFP interneuron anatomy and physiology. The data presented here show that dopamine loss has a temporally and regionally different effect on the number of striatal TH-eGFP interneurons. Several electrophysiological parameters of TH-eGFP interneurons show profound changes in dopamine-depleted striatum, such as reduction in plateau potentials and increase in spontaneous synaptic inputs, which were accompanied by a significant increase in spine density on these neurons. Taken together, the findings in this thesis establish that TH-eGFP neurons are a distinct group of striatal interneurons that show differential anatomical patterning throughout the dorsal-ventral axis of the striatum and respond to striatal dopamine-loss in a qualitatively and quantitatively different manner than striatal projection neurons.