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Cell Rep. 2017 Aug 29;20(9):2156-2168. doi: 10.1016/j.celrep.2017.08.017.

Neto Auxiliary Subunits Regulate Interneuron Somatodendritic and Presynaptic Kainate Receptors to Control Network Inhibition.

Author information

1
Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, 35 Lincoln Drive, MSC 3715, Bethesda, MD 20892, USA.
2
Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, 35 Lincoln Drive, MSC 3715, Bethesda, MD 20892, USA. Electronic address: pelkeyk2@mail.nih.gov.
3
Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, 35 Lincoln Drive, MSC 3715, Bethesda, MD 20892, USA; Neuronal Oscillations Laboratory, Division for Neurogeriatrics, Center for Alzheimer Research, Department NVS, Karolinska Institutet, 17177 Stockholm, Sweden.
4
Neuronal Oscillations Laboratory, Division for Neurogeriatrics, Center for Alzheimer Research, Department NVS, Karolinska Institutet, 17177 Stockholm, Sweden.
5
Program in Neurosciences & Mental Health, Hospital for Sick Children, and Department of Physiology, University of Toronto, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
6
Lady Davis Research Institute, Jewish General Hospital and Departments of Human Genetics and Biochemistry, McGill University, Montreal, QC H3T 1E2, Canada.
7
Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, 35 Lincoln Drive, MSC 3715, Bethesda, MD 20892, USA. Electronic address: mcbainc@mail.nih.gov.

Abstract

Although Netos are considered auxiliary subunits critical for kainate receptor (KAR) function, direct evidence for their regulation of native KARs is limited. Because Neto KAR regulation is GluK subunit/Neto isoform specific, such regulation must be determined in cell-type-specific contexts. We demonstrate Neto1/2 expression in somatostatin (SOM)-, cholecystokinin/cannabinoid receptor 1 (CCK/CB1)-, and parvalbumin (PV)-containing interneurons. KAR-mediated excitation of these interneurons is contingent upon Neto1 because kainate yields comparable effects in Neto2 knockouts and wild-types but fails to excite interneurons or recruit inhibition in Neto1 knockouts. In contrast, presynaptic KARs in CCK/CB1 interneurons are dually regulated by both Neto1 and Neto2. Neto association promotes tonic presynaptic KAR activation, dampening CCK/CB1 interneuron output, and loss of this brake in Neto mutants profoundly increases CCK/CB1 interneuron-mediated inhibition. Our results confirm that Neto1 regulates endogenous somatodendritic KARs in diverse interneurons and demonstrate Neto regulation of presynaptic KARs in mature inhibitory presynaptic terminals.

KEYWORDS:

cholecystokinin; hippocampus; interneuron; kainite; neto1; neto2; parvalbumin; somatostatin

PMID:
28854365
PMCID:
PMC5600503
DOI:
10.1016/j.celrep.2017.08.017
[Indexed for MEDLINE]
Free PMC Article

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