Activity-dependent tuning of intrinsic excitability in mouse and human neurogliaform cells
- Laboratory of Cellular and Synaptic Physiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States
- Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, United States
Figures
Figure 1 with 2 supplements
Barrage firing (BF) is evolutionary conserved in human NGFCs.
(A,C) Biocytin reconstruction of mouse (dendrites in black; axon in gray) and human NGFCs (dendrites in black; axon in orange) located in superficial regions of hippocampus (stratum lacunosum …
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Figure 1—source data 1
Data plotted in Figure 1.
- https://cdn.elifesciences.org/articles/57571/elife-57571-fig1-data1-v2.xlsx
Figure 1—figure supplement 1
Privileged induction of barrage firing in mouse and human NGFCs.
(A, B) Confocal mages of biocytin filled cortico-hippocampal NGFCs and non-NGFCs in stratum lacunosum-moleculare (SLM) and Layer I. Insets show firing patterns of non-NGFCs to suprathreshold current …
Figure 1—figure supplement 2
Induction of multiple barrage firing episodes in individual mouse and human NGFCs.
(A) Single trace example showing the inability to elicit prolonged BF episodes in single NGFC following immediate continuation of the induction protocol (30 × 10 Hz induction; see main Figure 1 for …
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Figure 1—figure supplement 2—source data 1
Data plotted in Figure 1—figure supplement 2.
- https://cdn.elifesciences.org/articles/57571/elife-57571-fig1-figsupp2-data1-v2.xlsx
Figure 2
Short-term potentiation of somatic-depolarization driven excitability (STP-SE) in mouse and human NGFCs after cessation of BF.
(A) Single example voltage traces in response to increasing square wave somatic depolarizing current injections before and after induction of BF. Values under each pair of traces (Pre-BF and …
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Figure 2—source data 1
Data plotted for Figure 2.
- https://cdn.elifesciences.org/articles/57571/elife-57571-fig2-data1-v2.xlsx
Figure 3 with 1 supplement
STP-SE in mouse and human NGFCs occurs in the absence of BF.
(A–C) Single example time course of the conditioning protocol employed to elicit STP-SE in mouse and human NGFCs. Action potential output was elicited to a test rheobase depolarizing current …
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Figure 3—source data 1
Data plotted for Figure 3.
- https://cdn.elifesciences.org/articles/57571/elife-57571-fig3-data1-v2.xlsx
Figure 3—figure supplement 1
Inability to induce STP-SE in a subpopulation of NGFCs and all non-NGFCs tested.
(A-D) Time course traces demonstrating the inability of a single example mouse NGFC and non-NGFC to express STP-SE. Traces in B and D are magnified for clarity at the time points in the induction …
Figure 4
Pharmacological block of a subthreshold transient K+-conductance mimics the AP latency and threshold modulation seen in STP-SE.
(A) Single example voltage trace to a depolarizing current injection (120 pA) in the presence of 1 μm TTX and 200 μm NiCl2 to block voltage gated Na+ and low-threshold activated Ca2+ channels, …
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Figure 4—source data 1
Data plotted for Figure 4.
- https://cdn.elifesciences.org/articles/57571/elife-57571-fig4-data1-v2.xlsx
Figure 5
Functional availability of IKA modulates intrinsic excitability and induction requirements of STP-SE.
(A) Single trace examples showing the effect of DTX (top traces), high 4-AP (middle traces) and with K+-gluconate intracellular solution without (control; bottom left trace) vs. 4-AP (intra-4-AP; …
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Figure 5—source data 1
Data plotted for Figure 5.
- https://cdn.elifesciences.org/articles/57571/elife-57571-fig5-data1-v2.xlsx
Figure 6 with 2 supplements
IKA in NGFCs is predominantly mediated by Kv4-subunit containing channels.
(A) Uniform Manifold Approximation and Projection (UMAP) plot of RNAseq data publicly available from the Allen Brain Institute (see Materials and methods for details) highlighting clusters …
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Figure 6—source data 1
Data plotted for Figure 6.
- https://cdn.elifesciences.org/articles/57571/elife-57571-fig6-data1-v2.xlsx
Figure 6—figure supplement 1
Delineation of mouse cortico-hippocampal cell clusters obtained from publicly available Allen Brain Institute scRNAseq data.
(A) Uniform Manifold Approximation and Projection (UMAP) dimension reductionality of ~76,000 single-cell transcriptomes, depicting the clustering of broad cell types. (B) Clustering of CGE and …
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Figure 6—figure supplement 1—source data 1
Data plotted for Figure 6—figure supplement 1.
- https://cdn.elifesciences.org/articles/57571/elife-57571-fig6-figsupp1-data1-v2.xlsx
Figure 6—figure supplement 2
Comparison of subthreshold Kv1 and Kv4 subunit gene expression between mouse and human NGFCs and other IN subtypes.
(A,B) mRNA expression levels of Kcna1, Kcnd2 and Kcnd3 in neural cell types. Data are from publicly available resources from the Allen Brain Institute and the McCarroll Laboratory, Harvard Medical …
Figure 7 with 1 supplement
STP-SE manifests as an increase in afferent recruitment of NGFCs via enhanced E-S coupling.
(A) Single traces showing the effect of AmmTx3 (500 nM) on EPSC (top traces) and corresponding EPSP (bottom trace) in a hippocampal NGFC in response to electrical stimulation of SLM afferent fibers …
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Figure 7—source data 1
Data plotted for Figure 7.
- https://cdn.elifesciences.org/articles/57571/elife-57571-fig7-data1-v2.xlsx
Figure 7—figure supplement 1
E-S coupling potentiation not attributed to modulation of spontaneous EPSC parameters.
(A) Traces showing spontaneous AMPA-receptor-mediated EPSCs (top) under baseline conditions (gray) and immediately after cessation of a 4th BF episode (post-BF4; black) elicited in a given NGFC. …
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Figure 7—figure supplement 1—source data 1
Data plotted for Figure 7—figure supplement 1.
- https://cdn.elifesciences.org/articles/57571/elife-57571-fig7-figsupp1-data1-v2.xlsx
Author response image 1
No change in absolute peak of action potentials before and during STP-SE.
Black and orange data are from mouse (n = 9) and human(n = 4) NGFCs, respectively.
Author response image 2
Single example illustrating a reversal in the modulation of AP output following STP-SE induction.
Author response image 3
Changes in electrotonic distance of AIS is not a prerequisite for heightened intrinsic excitability observed during STP-SE.
Values above 2nd derivative plots denote numbers of NGFCS displaying the changes highlighted. Black and orange data are from mouse (n = 9) and human(n = 4) NGFCs, respectively.
