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Sub-synaptic localization of Cav3.1 T-type calcium channels in the thalamus of normal and parkinsonian monkeys

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Abstract

T-type calcium channels (Cav3) are key mediators of thalamic bursting activity, but also regulate single cells excitability, dendritic integration, synaptic strength and transmitter release. These functions are strongly influenced by the subcellular and subsynaptic localization of Cav3 channels along the somatodendritic domain of thalamic cells. In Parkinson’s disease, T-type calcium channels dysfunction in the basal ganglia-receiving thalamic nuclei likely contributes to pathological thalamic bursting activity. In this study, we analyzed the cellular, subcellular, and subsynaptic localization of the Cav3.1 channel in the ventral anterior (VA) and centromedian/parafascicular (CM/Pf) thalamic nuclei, the main thalamic targets of basal ganglia output, in normal and parkinsonian monkeys. All thalamic nuclei displayed strong Cav3.1 neuropil immunoreactivity, although the intensity of immunolabeling in CM/Pf was significantly lower than in VA. Ultrastructurally, 70–80 % of the Cav3.1-immunoreactive structures were dendritic shafts. Using immunogold labeling, Cav3.1 was commonly found perisynaptic to asymmetric and symmetric axo-dendritic synapses, suggesting a role of Cav3.1 in regulating excitatory and inhibitory neurotransmission. Significant labeling was also found at non-synaptic sites along the plasma membrane of thalamic neurons. There was no difference in the overall pattern and intensity of immunostaining between normal and parkinsonian monkeys, suggesting that the increased rebound bursting in the parkinsonian state is not driven by changes in Cav3.1 expression. Thus, T-type calcium channels are located to subserve neuronal bursting, but also regulate glutamatergic and non-glutamatergic transmission along the whole somatodendritic domain of basal ganglia-receiving neurons of the primate thalamus.

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Acknowledgments

This project was supported through grants from the NIH/NINDS [R01 NS054976 (TW/YS) and P50 NS071669 (Udall Center Grant, TW/YS)], a grant from the NIH BP ENDURE [SP00010548 (EC/YS)] and a grant from the NIH/ORIP to the Yerkes Center (P51 OD011132). We thank Susan Jenkins for expert technical assistance.

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  1. Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA, 30329, USA

    Erdong Chen, Jean-Francois Paré, Thomas Wichmann & Yoland Smith

  2. Udall Center of Excellence for Parkinson’s Disease Research, Emory University, Atlanta, GA, 30322, USA

    Erdong Chen, Jean-Francois Paré, Thomas Wichmann & Yoland Smith

  3. Department of Neurology, Emory University, Atlanta, GA, 30322, USA

    Thomas Wichmann & Yoland Smith

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  1. Erdong Chen
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Chen, E., Paré, JF., Wichmann, T. et al. Sub-synaptic localization of Cav3.1 T-type calcium channels in the thalamus of normal and parkinsonian monkeys. Brain Struct Funct 222, 735–748 (2017). https://doi.org/10.1007/s00429-016-1242-9

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