Voltage Gated Calcium Channel Activation by Backpropagating Action Potentials Downregulates NMDAR Function

Anne-Kathrin Theis; Balázs Rózsa; Gergely Katona; Dietmar Schmitz; Friedrich W Johenning

doi:10.3389/fncel.2018.00109

Voltage Gated Calcium Channel Activation by Backpropagating Action Potentials Downregulates NMDAR Function

Front Cell Neurosci. 2018 Apr 23:12:109. doi: 10.3389/fncel.2018.00109. eCollection 2018.

Authors

Anne-Kathrin Theis¹, Balázs Rózsa^{2

3}, Gergely Katona³, Dietmar Schmitz^{1

4

5

6

7}, Friedrich W Johenning^{1

4

8}

Affiliations

¹ Neuroscience Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany.
² Laboratory of 3D Functional Network and Dendritic Imaging, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
³ Faculty of Information Technology and Bionics, Pázmány Péter University, Budapest, Hungary.
⁴ Einstein Center for Neuroscience, Berlin, Germany.
⁵ Bernstein Center for Computational Neuroscience, Berlin, Germany.
⁶ Cluster of Excellence "Neurocure", Berlin, Germany.
⁷ DZNE-German Center for Neurodegenerative Disease, Berlin, Germany.
⁸ Berlin Institute of Health (BIH), Berlin, Germany.

Abstract

The majority of excitatory synapses are located on dendritic spines of cortical glutamatergic neurons. In spines, compartmentalized Ca²⁺ signals transduce electrical activity into specific long-term biochemical and structural changes. Action potentials (APs) propagate back into the dendritic tree and activate voltage gated Ca²⁺ channels (VGCCs). For spines, this global mode of spine Ca²⁺ signaling is a direct biochemical feedback of suprathreshold neuronal activity. We previously demonstrated that backpropagating action potentials (bAPs) result in long-term enhancement of spine VGCCs. This activity-dependent VGCC plasticity results in a large interspine variability of VGCC Ca²⁺ influx. Here, we investigate how spine VGCCs affect glutamatergic synaptic transmission. We combined electrophysiology, two-photon Ca²⁺ imaging and two-photon glutamate uncaging in acute brain slices from rats. T- and R-type VGCCs were the dominant depolarization-associated Ca²⁺conductances in dendritic spines of excitatory layer 2 neurons and do not affect synaptic excitatory postsynaptic potentials (EPSPs) measured at the soma. Using two-photon glutamate uncaging, we compared the properties of glutamatergic synapses of single spines that express different levels of VGCCs. While VGCCs contributed to EPSP mediated Ca²⁺ influx, the amount of EPSP mediated Ca²⁺ influx is not determined by spine VGCC expression. On a longer timescale, the activation of VGCCs by bAP bursts results in downregulation of spine NMDAR function.

Keywords: NMDAR; calcium; dendritic spines; homeostatic synaptic plasticity; metaplasticity; synaptic transmission; two-photon microscopy; voltage gated Ca2+ channels (VGCCs).