Cell Reports
Volume 20, Issue 9, 29 August 2017, Pages 2156-2168
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Article
Neto Auxiliary Subunits Regulate Interneuron Somatodendritic and Presynaptic Kainate Receptors to Control Network Inhibition

https://doi.org/10.1016/j.celrep.2017.08.017Get rights and content
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Highlights

  • SOM, CCK/CB1, and PV interneurons express Neto1/2 in combination with GluK1/2/5

  • Neto1 is required for somatodendritic KAR-mediated excitation of interneurons

  • Both Netos regulate presynaptic KARs

  • Netos promote tonic KAR inhibition of CCK interneuron release by ambient glutamate

Summary

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

interneuron
kainite
hippocampus
parvalbumin
cholecystokinin
somatostatin
neto1
neto2

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