Dopaminergic and cholinergic modulation of striatal tyrosine hydroxylase interneurons
Introduction
Until recently, the neostriatum has been thought to contain only a few types of GABAergic interneurons in comparison to the large diversity of GABAergic cell types in the neocortex or the hippocampus (Freund, 1996, Tepper et al., 2010, DeFelipe et al., 2013). This picture changed significantly with the introduction of transgenic reporter mouse lines that revealed the existence of 5 new electrophysiologically distinct cell types, more than doubling the number of interneuron classes recognized in this brain area (Ibáñez-Sandoval et al., 2010, Ibáñez-Sandoval et al., 2011; Unal et al., 2011). In addition to a neuropeptide Y (NPY) expressing neuron described in a NPY-GFP line (Ibáñez-Sandoval et al., 2011), the newly discovered interneurons include 4 additional types of GABAergic neurons that were termed TH-interneurons (THINs) reflecting their initial identification in a TH-EGFP strain (Ibáñez-Sandoval et al., 2010; Unal et al., 2011). The function of THINs remains unclear. Their small population size and connectivity place some important constraints on the possible function of these neurons. On particularly interesting possibility is that these neurons may distribute intra- and extrastriatal neuromodulatory signals to projection neurons.
In the neostriatum, dopamine (DA) and acetylcholine (ACh) are 2 major neuromodulators that exert pronounced effects on most functions of the basal ganglia. Here we investigated how these neuromodulators or control the intrinsic electrophysiological properties of THINs. Since preliminary experiments indicated that the most salient effect of these modulators was the triggering and enhancement of a semi-stable depolarizing state we characterized in more detail this important dynamic feature of THINs.
Section snippets
Subjects
We used transgenic mice Tg (Th-EGFP) DJ76Gsat/Mmmc (GENSAT; Gong et al., 2003), obtained from the Mutant Mouse Regional Resource Center at UCLA and bred in our colony at Rutgers for all experiments. Hemizygous progeny were mated to wild type FVB or Swiss Webster mice each generation thereafter. All offspring were genotyped from tail samples and only those expressing the EGFP transgene were used in these experiments. Henceforth these mice are referred to as EGFP-TH mice.
All procedures were
Electrophysiological and anatomical properties of striatal TH interneurons
Ex vivo whole-cell recordings were obtained in current clamp mode from fluorescent neurons in the striatum of adult EGFP-TH mice. In agreement with previously reported data (Ibáñez-Sandoval et al., 2010), several distinct subtypes of THINs could be characterized on the basis of their intrinsic electrophysiological properties (input resistance Rin), resting membrane potential (RMP), action potential duration at half-amplitude (AP50%), their ability or inability to maintain firing throughout
Discussion
The present experiments examined the effects of DA and ACh on striatal THINs. The first principal finding was that intrinsic PPs elicited by depolarizing pulses in Type I and Type II THINs were facilitated by DA acting through a D1/D5-like DA receptor, and that in Type I and Type II THINs that did not exhibit intrinsic PPs, as well as in Type IV THINs that were never observed to exhibit intrinsic PPs, these plateaus could be elicited by D1/D5 receptor stimulation. In all cases, the PPs were
Acknowledgments
This research was supported, in part, by NIH Grants 5R01NS034865 (J M T.), 1R01NS072950 (T K. and J.M. T.) and Rutgers University. We thank Fulva Shah and Parth Gandhi for excellent technical assistance and Leticia Maldonado for the biocytin reconstruction in Figure 1A.
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Cited by (0)
- 1
Present address: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, Av., Venustiano Carranza, San Luis Potosí, Mexico.
- 2
Present address: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.