Striatal TH Interneurons
There are at least 3,000 EGFP-TH+ GABAergic interneurons in each striatal hemisphere. In this fluorescent micrograph, EGFP+ TH interneurons are indicated by white arrows. Unal and Tepper, unpublished.
Striatal TH interneurons transduced with ChR2-YFP following intrastriatal injection of AAV-2 in a TH-cre mouse previously treated with 6-OHDA. All the cells and processes visible derive from intrinsic striatal TH interneurons, not from the nigrostriatal pathway. Note the density of the local innervation of by the TH interneurons. Tepper, unpublished.
There are 4 electrophysiologically distinct subtypes of EGFP-TH interneurons in the striatum
Whole cell recordings revealed that there are 4 electrophysiologically distinct subtypes of striatal TH interneuron, whose intrinsic properties are shown in the table below. Note that the Type I is by far the most abundant subtype, and together Type I and Type IV cells account for almost 80% of all striatal TH interneurons. From Ibáñez-Sandoval O, Tecuapetla, F., Unal, B., Shah, F., Koós, T. & Tepper, J.M. (2010) Electrophysiological and morphological characteristics and synaptic connectivity of tyrosine hydroxylase expressing neurons in adult mouse striatum. J. Neurosci. 30:6999-7016.
Biocytin filled electrophysiologically identified Type I striatal TH interneuron. Note sparse spine-like dendritic specializations. From Ibáñez-Sandoval O, Tecuapetla, F., Unal, B., Shah, F., Koós, T. & Tepper, J.M. (2010) Electrophysiological and morphological characteristics and synaptic connectivity of tyrosine hydroxylase expressing neurons in adult mouse striatum. J. Neurosci. 30:6999-7016.
Synaptic interaction between an EGFP-TH Type II interneuron (identified by EGFP fluorescence in A and electrophysiologically in B3 and D) and a spiny cell. The Type II interneuron powerfully inhibits the spiny cell. Single spikes evoked in the Type II interneuron produce IPSCs in the spiny neuron (C) and a pair of evoked presynaptic spikes in the interneuron delays spikes in the spiny neuron by ~ 100 ms (B1, 2). From Ibáñez-Sandoval O, Tecuapetla, F., Unal, B., Shah, F., Koós, T. & Tepper, J.M. (2010) Electrophysiological and morphological characteristics and synaptic connectivity of tyrosine hydroxylase expressing neurons in adult mouse striatum. J. Neurosci. 30:6999-7016.
Many TH interneurons express a spontaneous plateau potential. The plateau potential is sensitive to dopamine and D1/D5 agonists or antagonists. This excitatory effect is due to facilitation of ICAN. From Ibáñez et al., 2015.
THINSs are not immunoreactive for the DA transporter
Midbrain dopaminergic neurons in the substantia nigra pars compacta at low magnification (top row) and higher magnifcation (bottom row) show greeen EGFP-TH staining in a TH-EGFP mouse and the same section in red (middle) shows DAT immunostaining. The rightmost panels show the overlap, demonstrating that all EFGP+ neurons also stain for DAT, as expected for dopaminergic neurons. Xenias, H., Ibáñez-Sandoval, O., Koós, T.,& Tepper, J.M. (2015) Are striatal tyrosine hydroxylase interneurons dopaminergic? J. Neurosci. 35:6584-6599.
THINSs are not immunoreactive for DA
In marked contrast to substantia nigra dopaminergic neurons shown above, striatal EGFP-TH interneurons do not stain for the DAT, either on control side or ipsilateral to a 6-OHDA lesion destroying the nigrostriatal pathway suggesting strongly that they are not dopaminergic. Xenias, H., Ibáñez-Sandoval, O., Koós, T.,& Tepper, J.M. (2015) Are striatal tyrosine hydroxylase interneurons dopaminergic? J. Neurosci. 35:6584-6599.
THINs do not release dopamine
Striatal TH interneurons are NOT dopaminergic. A. Unilateral destruction of nigrostriatal pathway in a TH-cre mouse. B. AAV2-ChR2-YFP is injected bilaterally into striatum where it transduces only striatal TH interneurons. Inset shows depolarization and spiking of a ChR2-YFP-transduced striatal TH interneuron by a 2 ms blue light pulse. C1. Electrical stimulation of striatum on intact side activates both striatal TH interneurons and nigrostriatal pathway, and results in a large DA release measured by fast scan cyclic voltammetry. C2. On lesioned side, where only striatal TH interneurons survive, there is no measureable DA release.C3, C4. Optical stimulation, which activates striatal TH interneurons as in B, never produces any DA release. Thus, striatal TH interneurons are NOT dopaminergic. Xenias, H., Ibáñez-Sandoval, O., Koós, T.,& Tepper, J.M. (2015) (2015) Are striatal tyrosine hydroxylase interneurons dopaminergic? J. Neurosci. 35:6584-6599.
Top left: THINs transfected with ChR2-EYFPspiking after a blue light pulse Top right: Schematic representing specificity of the connectivity of THINs. Panels from top to bottom: LTS interneurons receive a strong inhibitory input from THINs, while NGF and FSI do not. CINs receive inhibitory input from THINs. Assous et al. (2017).
THINs, like other striatal GABAergic interneurons, selectively innervate only a subset of other interneurons
