Presynaptic NMDA Receptors Influence Ca2+ Dynamics by Interacting with Voltage-Dependent Calcium Channels during the Induction of Long-Term Depression.

Neubauer, Florian B; Min, Rogier; Nevian, Thomas (2022). Presynaptic NMDA Receptors Influence Ca2+ Dynamics by Interacting with Voltage-Dependent Calcium Channels during the Induction of Long-Term Depression. Neural plasticity, 2022, p. 2900875. Hindawi 10.1155/2022/2900875

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Spike-timing-dependent long-term depression (t-LTD) of glutamatergic layer (L)4-L2/3 synapses in developing neocortex requires activation of astrocytes by endocannabinoids (eCBs), which release glutamate onto presynaptic NMDA receptors (preNMDARs). The exact function of preNMDARs in this context is still elusive and strongly debated. To elucidate their function, we show that bath application of the eCB 2-arachidonylglycerol (2-AG) induces a preNMDAR-dependent form of chemically induced LTD (eCB-LTD) in L2/3 pyramidal neurons in the juvenile somatosensory cortex of rats. Presynaptic Ca2+ imaging from L4 spiny stellate axons revealed that action potential (AP) evoked Ca2+ transients show a preNMDAR-dependent broadening during eCB-LTD induction. However, blockade of voltage-dependent Ca2+ channels (VDCCs) did not uncover direct preNMDAR-mediated Ca2+ transients in the axon. This suggests that astrocyte-mediated glutamate release onto preNMDARs does not result in a direct Ca2+ influx, but that it instead leads to an indirect interaction with presynaptic VDCCs, boosting axonal Ca2+ influx. These results reveal one of the main remaining missing pieces in the signaling cascade of t-LTD at developing cortical synapses.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology

UniBE Contributor:

Nevian, Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2090-5904

Publisher:

Hindawi

Language:

English

Submitter:

Pubmed Import

Date Deposited:

21 Feb 2022 11:22

Last Modified:

05 Dec 2022 16:09

Publisher DOI:

10.1155/2022/2900875

PubMed ID:

35178084

BORIS DOI:

10.48350/165768

URI:

https://boris.unibe.ch/id/eprint/165768

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