A class-specific effect of dysmyelination on the excitability of hippocampal interneurons
- INMED, INSERM, Aix Marseille Université, France
- INSERM, Institut du Fer à Moulin, Sorbonne Université, Faculté des Sciences et Ingénierie, France
- Department of Basic Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, University of Crete, Greece
Figures
Figure 1 with 4 supplements
4.1B KO mice show strong reduction of myelin in the adult hippocampus.
(A–B) Hippocampal vibratome sections from P35 wild-type and 4.1B KO mice immunostained for MBP as a myelin marker. Note the lack of myelin sheaths in the CA1 stratum radiatum of the hippocampus …
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Figure 1—source data 1
Length of myelinated axons and paranode density in the different layers of the CA1 hippocampus of wild-type and 4.1B KO mice.
- https://cdn.elifesciences.org/articles/86469/elife-86469-fig1-data1-v2.xlsx
Figure 1—figure supplement 1
Myelin pattern in the CA1 hippocampus of Cntn2-/-, Cntnap2-/-, and 4.1B KO mice.
CA1 hippocampus stained for MBP (green). (A, B, G, H) Lhx6-Cre;tdTomato mice: control (A, G), Cntn2-/- (B) and 4.1B KO (H) mice at P70 showing axons of PV and SST cells expressing the tdTomato …
Figure 1—figure supplement 2
Myelin pattern is preserved in the cortex of 4.1B KO mice at P70.
Coronal brain sections showing the somato-sensory cortex of Lhx6-Cre;tdTomato control (A) and 4.1B KO (B) mice at P70. Double-staining for MBP (Cyan) and Caspr (green). Note in the inset that the …
Figure 1—figure supplement 3
Myelin pattern alteration in the hippocampus of 4.1B KO mice at P25.
Hippocampus from P25 wild-type and 4.1B KO mice immunostained for MBP (grey) and caspr (green). Note the severe loss of myelin sheaths in the CA1 stratum radiatum of the 4.1B-deficient hippocampus …
Figure 1—figure supplement 4
Myelin pattern alteration in the hippocampus of 4.1B KO mice at P180.
Hippocampus from P180 wild-type and 4.1B KO mice immunostained for MBP (grey). Note the severe loss of myelin sheaths in the CA1 stratum radiatum of the 4.1B-deficient hippocampus that persists at …
Figure 2
Parvalbumin and somatostatin axons are dysmyelinated in the 4.1B KO hippocampus.
(A–D) Hippocampal sections of wild-type and 4.1B KO mice immunostained for PV (A, B) or SST (C, D) at P35. (E, F) Quantification of the cell density/105 µm2 in the CA1 stratum oriens (SO) and …
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Figure 2—source data 1
Density of PV and SST cells and length of myelinated PV and SST axons in the hippocampus of wild-type and 4.1B KO mice.
- https://cdn.elifesciences.org/articles/86469/elife-86469-fig2-data1-v2.xlsx
Figure 3
The density of oligodendroglial cells is preserved in the 4.1B KO hippocampus.
Hippocampal sections of wild-type and 4.1B KO mice at P35 immunostained for MBP (blue), SST (red) and Olig2 (green) as a marker of the oligodendrocyte lineage. CA1 region (A, B) and dentate gyrus (C,…
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Figure 3—source data 1
Density of Olig2-positive cells in the CA1 hippocampus and dentate gyrus of wild-type and 4.1B KO mice.
- https://cdn.elifesciences.org/articles/86469/elife-86469-fig3-data1-v2.xlsx
Figure 4
4.1B is enriched at paranodes of GABAergic axons and involved in internodal elongation.
(A) Schematic drawing to depict the role of 4.1B at paranodes mediating the anchorage between Caspr and the ßII-spectrin at the boundary with the nodal ßIV-spectrin. (B) Distribution of internodal …
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Figure 4—source data 1
Internodal length of myelinated axons in the CA1 hippocampus of control and 4.1B KO mice.
- https://cdn.elifesciences.org/articles/86469/elife-86469-fig4-data1-v2.xlsx
Figure 5 with 1 supplement
Misplacement of heminodal and nodal of Nav channels in 4.1B-deficient GABAergic axons.
Hippocampal sections of P70 Lhx6-Cre;tdTomato control and 4.1B KO mice were immunostained for MBP (blue), Caspr (white) and panNav (green). tdTomato expressed in Lhx6-positive cells or PV …
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Figure 5—source data 1
Length and positioning of Nav channels in GABAergic axons of control and 4.1B KO mice.
- https://cdn.elifesciences.org/articles/86469/elife-86469-fig5-data1-v2.xlsx
Figure 5—figure supplement 1
Myelination and positioning of Nav channels are altered in 4.1B-deficient GABAergic axons.
Hippocampal sections of P70 Lhx6-Cre;tdTomato control and 4.1B KO mice were immunostained for MBP (blue), Caspr (white) and panNav (green). tdTomato expressed in Lhx6-positive cells is in red. (A) a …
Figure 6
The clustering of juxtaparanodal Kv1 channels is reduced in GABAergic axons from Cntn2-/-, Cntnap2-/-, and 4.1 KO mice.
Immunostaining for Kv1.2 channels in GABAergic axons of the stratum radiatum in CA1 at P70. (A) Juxtaparanodal clustering of Kv1 channels in Lhx6-Cre;tdTomato control mouse immunostained for MBP …
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Figure 6—source data 1
Juxtaparanodal clustering of Kv1 channels in PV axons of wild-type, Cntn2-/-, Cntnap2-/-, and 4.1 KO mice.
- https://cdn.elifesciences.org/articles/86469/elife-86469-fig6-data1-v2.xlsx
Figure 7
The excitability of SST interneurons in the stratum oriens is selectively decreased in 4.1B KO mice.
(A–G) Patch-clamp recordings of Lhx6-positive PV fast-spiking interneurons in the stratum pyramidale (SP). (A) Schematic illustration of basket and bistratified (BiC) cells in CA1 located in the SP …
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Figure 7—source data 1
Electrophysiological properties of Lhx6-positive PV fast-spiking interneurons in the stratum pyramidale from control and 4.1B KO mice.
- https://cdn.elifesciences.org/articles/86469/elife-86469-fig7-data1-v2.xlsx
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Figure 7—source data 2
Electrophysiological properties of Lhx6-positive interneurons in the stratum oriens from control and 4.1B KO mice.
- https://cdn.elifesciences.org/articles/86469/elife-86469-fig7-data2-v2.xlsx
Figure 8
Structural modification of the AIS of SST interneurons in 4.1B KO mice.
(A–C) Analysis of somatic action potentials (APs). Representative examples illustrating the voltage waveform of the AP (A1 and B1; in mV) from a control (A1) and a 4.1B KO neurons (B1). Below are …
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Figure 8—source data 1
Length and onset of AIS measured for AnkyrinG immunostaining of SST interneurons in the stratum oriens of wild-type and 4.1B KO mice.
- https://cdn.elifesciences.org/articles/86469/elife-86469-fig8-data1-v2.xlsx
Figure 9
Inhibitory inputs onto CA1 pyramidal neurons are affected in 4.1B KO mice.
(A) Schematic illustration of inhibitory inputs onto the soma, proximal and distal dendrites of pyramidal cells. (B) Example traces of sIPSCs onto CA1 pyramidal neurons of control and 4.1B KO mice. …
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Figure 9—source data 1
Amplitude and frequency of sIPSCs onto CA1 pyramidal neurons in the control and 4.1B KO mice.
- https://cdn.elifesciences.org/articles/86469/elife-86469-fig9-data1-v2.xlsx
Videos
Video 1
O-LM axons are partly myelinated in the lower and upper regions of the stratum radiatum in 4.1B KO mice at P35.
Double-staining for MBP (pink) and SST (green). 25-z steps of 1 µm.
Video 2
O-LM axons crossing the stratum radiatum are myelinated in wild-type mice at P35.
Double-staining for MBP (pink) and SST (green). 25-z steps of 1 µm.
Tables
Table 1
Intrinsic electrophysiological properties of fast-spiking Lhx6-interneurons in the stratum pyramidale.
| Control (mean ± SEM, n=9) | 4.1B KO (mean ± SEM, n=10) | MW test, p value | |
|---|---|---|---|
| Passive properties | |||
| Resting membrane potential (mV) | 57.67±3.26 | 60.50±1.99 | MW, 0.6748 |
| Input resistance (MΩ) | 360.11±52.46 | 346.20±37.77 | MW, 0.8421 |
| Rheobase (pA) | 36.67±5.00 | 28.80±6.33 | MW, 0.1305 |
| Action potential parameters | |||
| Amplitude (mV) | 60.42±3.47 | 56.54±2.79 | MW, 0.3882 |
| Area (mV.s) | 58.69±6.00 | 56.44±4.74 | MW, 0.4967 |
| Half-width (ms) | 0.92±0.07 | 0.94±0.06 | MW, 0.9838 |
| Threshold (mV) | 46.79±2.28 | 46.60±1.78 | MW, 0.9682 |
| AHP area (mV.ms) | 185.39±54.05 | 276.69±42.71 | MW, 0.2775 |
| AHP peak (mV) | 10.35±1.85 | 10.65±1.10 | MW, 0.6607 |
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Statistical differences between groups were calculated with a Mann-Whitney test (MW). Control: n=9 mice; 4.1B KO: n=6 mice.
Table 2
Intrinsic electrophysiological properties of Lhx6-interneurons in the stratum oriens.
| Control (mean ± SEM, n=9) | 4.1B KO (mean ± SEM, n=17) | MW test, p value | |
|---|---|---|---|
| Passive properties | |||
| Resting membrane potential (mV) | 62.17±2.93 | 57.59±1.65 | MW, 0.2527 |
| Input resistance (MΩ) | 357.33±30.30 | 278.94±21.12 | MW, 0.0236* |
| Rheobase (pA) | 38.25±5.73 | 52.65±5.79 | MW, 0.1221 |
| Action potential parameters | |||
| Amplitude (mV) | 65.34±1.84 | 64.06±1.94 | MW, 0.6788 |
| Area (mV.s) | 111.44±17.87 | 104.80±8.93 | MW, 0.8788 |
| Half-width (ms) | 1.61±0.25 | 1.63±0.16 | MW, 0.5929 |
| Threshold (mV) | 45.69±1.83 | 43.65±1.43 | MW, 0.5558 |
| AHP area (mV.ms) | 351.29±58.99 | 526.59±53.50 | MW, 0.0380* |
| AHP peak (mV) | 12.57±1.79 | 16.24±1.25 | MW, 0.1280 |
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Statistical differences between groups were calculated with a Mann-Whitney test (MW). Control: n=9 mice; 4.1B KO: n=8 mice.
