1. Neuroscience

Deletion of KCNQ2/3 potassium channels from PV+ interneurons leads to homeostatic potentiation of excitatory transmission

  1. Heun Soh
  2. Suhyeorn Park
  3. Kali Ryan
  4. Kristen Springer
  5. Atul Maheshwari  Is a corresponding author
  6. Anastasios V Tzingounis  Is a corresponding author
  1. University of Connecticut, United States
  2. Baylor College of Medicine, United States
https://doi.org/10.7554/eLife.38617
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Cite this article
  1. Heun Soh
  2. Suhyeorn Park
  3. Kali Ryan
  4. Kristen Springer
  5. Atul Maheshwari
  6. Anastasios V Tzingounis
(2018)
Deletion of KCNQ2/3 potassium channels from PV+ interneurons leads to homeostatic potentiation of excitatory transmission
eLife 7:e38617.
https://doi.org/10.7554/eLife.38617
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4 figures, 1 table and 1 additional file

Figures

Figure 1
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Ablation of Kcnq2/3 channels from PV+/SST+interneurons leads to increased excitatory transmission.

(a) Top, representative sEPSC and sIPSC traces recorded from mouse CA1 pyramidal neurons (P15–P19) in acute hippocampal slices from control (number of animals = 8) and either Kcnq2/3 interneuron …

https://doi.org/10.7554/eLife.38617.002
Figure 1—source data 1

Source data for Figure 1.

https://doi.org/10.7554/eLife.38617.003
Figure 2 with 3 supplements
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Loss of KCNQ2/3 activity leads to increased excitability of PV+interneurons.

(a) Top, representative voltage responses from a +150 pA current injection step (1 s) in PV- and SST-like interneurons in either the CA1 region of the hippocampus (P12–P17) or L2/3 of the …

https://doi.org/10.7554/eLife.38617.004
Figure 2—source data 1

Source data for Figure 2.

https://doi.org/10.7554/eLife.38617.010
Figure 2—figure supplement 1
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FISH shows presence of KCNQ2 and KCNQ3 in SST+interneurons.

Confocal micrographs of coronal sections of CA1 region of wild-type mice. Micrographs shows co-localization of mRNA for somatostatin, KCNQ2 and KCNQ3. All micrographs have been counterstained with …

https://doi.org/10.7554/eLife.38617.005
Figure 2—figure supplement 2
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PV:Kcnq2/3 null interneurons could differ in their intrinsic excitability properties.

Top, representative voltage responses to a series of current injection steps (1 s) in PV+ interneurons in the CA1 region of the hippocampus (P16–P25). We found that Kcnq2/3 null PV+ interneurons …

https://doi.org/10.7554/eLife.38617.006
Figure 2—figure supplement 2—source data 1

Source data for Figure 2—figure supplement 2.

https://doi.org/10.7554/eLife.38617.007
Figure 2—figure supplement 3
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The pan-KCNQ blocker XE991 increases PV+interneuron excitability.

Left, representative voltage responses from a + 200 pA current injection step (1 s; Vh=-75 to −77 mV) in PV+ interneurons (Pvalb-Cre;Kcnq2+/+;Ai9) from the CA1 region of the hippocampus (P23–P25) …

https://doi.org/10.7554/eLife.38617.008
Figure 2—figure supplement 3—source data 1

Source data for Figure 2—figure supplement 3.

https://doi.org/10.7554/eLife.38617.009
Figure 3
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Ablation of Kcnq2 from PV+ interneurons leads to increased excitatory transmission in pyramidal neurons.

For simplicity we refer Pvalb-Cre;Kcnq2;Ai9 mice in the figure as Pvalb-Cre;Kcnq2f/f or Pvalb-Cre;Kcnq2+/+. (a) Left, representative voltage responses from a + 200 pA current injection step (1 s; …

https://doi.org/10.7554/eLife.38617.011
Figure 3—source data 1

Source data for Figure 3.

https://doi.org/10.7554/eLife.38617.012
Figure 4
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In vivo hyperexcitability with loss of Kcnq2 in PV-expressing interneurons.

(a) Using simultaneous video-EEG monitoring, Stage five onset was defined as the latency to rearing and falling with forelimb clonus, associated with bilateral epileptiform activity on EEG. (b) Loss …

https://doi.org/10.7554/eLife.38617.013
Figure 4—source data 1

Source data for Figure 4.

https://doi.org/10.7554/eLife.38617.014

Tables

Key resources table
Reagent type
(species) or resource		DesignationSource or referenceIdentifiersAdditional information
Gene (Mus musculus)Kcnq2NANCBI_Gene:16536;
MGI:1309503
Gene (Mus musculus)Kcnq3NANCBI_Gene:110862;
MGI:1336181
Strain, strain
background (M. musculus,
Emx1IRESCre, C57BL/6J
background)		B6.129S2-Emx1tm1(cre)Krj /JPMID: 12151506RRID:IMSR_JAX:005628
Strain, strain
background (M. musculus,
Nkx2.1-Cre,
C57BL/6J background)		C57BL/6J-Tg
(Nkx2-1-cre)2Sand/J		PMID: 17990269RRID:IMSR_JAX:008661
Strain, strain
background (M. musculus,
Sst-IRES-Cre, C57BL/6J
background)		Ssttm2.1(cre)Zjh/JPMID: 21943598RRID:IMSR_JAX:013044
Strain, strain
background (M. musculus,
Pvalb-Cre, C57BL/6J
background)		B6;129P2-Pvalbtm1(cre)Arbr/JPMID: 15836427RRID:IMSR_JAX:008069
Strain, strain
background (M. musculus,
tdTomato reporter Ai9,
C57BL/6J background)		B6.Cg-Gt(ROSA)
26Sortm9(CAG-tdTomato)Hze/J		PMID: 20023653RRID:IMSR_JAX:007909
Strain, strain
background (M. musculus,
Kcnq2f/f, C57BL/6J
background)		Kcnq2f/fPMID: 24719109N-A
Strain, strain
background (M. musculus,
Kcnq3f/f, C57BL/6J
background)		Kcnq3f/fPMID: 24719109N-A
AntibodyAlexa fluor 488
streptavidin		InvitrogenInvitrogen:S32354;
RRID:AB_2315383		(1:500)
Antibodyanti-Lucifer yellow
(rabbit polyclonal)		InvitrogenInvitrogen:A5750;
RRID:AB_2536190		(1:500)
Antibodyanti-Somatostatin
(rat monoclonal)		MilliporeMillipore:MAB354;
RRID:AB_2255365		(1:250)
AntibodyAlexa fluor 488
anti-rabbit secondary
(goat polyclonal)		InvitrogenInvitrogen:A11034;
RRID:AB_2576217		(1:500)
AntibodyAlexa fluor 647
anti-rat secondary
(goat polyclonal)		InvitrogenInvitrogen:A21247;
RRID:AB_141778		(1:500)
Sequence-based
reagent		somatostatin mRNA
probe (mouse); Mm-Sst-C1		ACDBioCat#:404631(1:50)
Sequence-based
reagent		parvalbumin mRNA
probe (mouse);
Mm-Pvalb-C1		ACDBioCat#:421931(1:50)
Sequence-based
reagent		tdTomato mRNA probe
(mouse); Mm-tdTomato-C3		ACDBioCat#:317041-C3(1:50)
Sequence-based
reagent		Kcnq2 mRNA probe
(mouse); Mm-Kcnq2-O1		ACDBio; this paperCat#:300031-C2(1:50); custom made
probe that targets exons
2–5 of Kcnq2
Sequence-based
reagent		Kcnq3 mRNA probe
(mouse); Mm-Kcnq3-O1		ACDBio; this paperCat#:300031-C3(1:50); custom made
probe that targets exons
2–5 of Kcnq2
Commercial
assay or kit		RNAscope Fresh Frozen
Multiplex Fluorescent kit		ACDBioCat#:320851
Chemical
compound, drug		CNQXAbcamab120017
Chemical
compound, drug		D-AP5Abcamab120003
Chemical
compound, drug		PicrotoxinAbcamab120315
Chemical
compound, drug		Tetrodotoxin; TTXAbcamab120054
Chemical
compound, drug		XE-991Abcamab120089
Chemical
compound, drug		Lucifer YellowSigmaCat#:B4261(0.1%)
Chemical
compound, drug		BiocytinMolecular ProbesCat#:L1177(0.05%)
Software, algorithmPrism 7GraphPadRRID:SCR_002798Version 7.03
Software, algorithmClampfit 10Molecular DevicesRRID:SCR_011323
Software, algorithmMinianalysisSynaptosoftRRID:SCR_002184
Software, algorithmOrigin 8 ProOriginLabRRID:SCR_014212Version 8.0951
Software, algorithmImageJNIHRRID:SCR_003070Version 2.0.0

Additional files

Transparent reporting form
https://doi.org/10.7554/eLife.38617.015

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