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Hippocampal Theta Input to the Amygdala Shapes Feedforward Inhibition to Gate Heterosynaptic Plasticity.

Bazelot M, Bocchio M, Kasugai Y, Fischer D, Dodson PD, Ferraguti F, Capogna M - Neuron (2015)

Bottom Line: These effects are mediated by GABAB receptors and change in the Cl(-) driving force.Hence, feedforward inhibition, known to enforce temporal fidelity of excitatory inputs, dominates hippocampus-amygdala interactions to gate heterosynaptic plasticity.VIDEO ABSTRACT.

View Article: PubMed Central - PubMed

Affiliation: MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3TH, UK.

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Activation of Hippocampal Inputs Provides FFI of BA PNs(A) Ex vivo cell-attached recording from a representative PN in response to single light pulses (20 superimposed sweeps, top; singularly represented in raster plot, bottom). Red circles denote spike negative peak.(B) Mean probability of firing of PNs (bins = 10 ms, black: mean, red: SEM; n = 24).(C) Whole-cell recording of the same cell as in (A) showing that the light pulse induced a PSP composed of an EPSP followed by a biphasic IPSP. On average, the peak amplitudes of the EPSP, early IPSP, and late IPSP were 8.9 ± 1 mV, 4.1 ± 0.8 mV, and 2.7 ± 0.6 mV (n = 24), respectively. Inset: Response to hyperpolarizing and depolarizing current injections showing stereotypic PN firing.(D) Cell-attached recording from a representative IN in response to a single light pulse (20 superimposed sweeps, top; singularly represented in raster plot, bottom). Blue circles denote spike negative peak.(E) Mean probability of firing of INs (bin = 10 ms, black: mean, red: SEM; n = 11).(F) Whole-cell recording of the same cell as in (D) showing that the light stimulation evoked a monophasic EPSP. On average, the peak amplitude of the EPSP was 8.1 ± 0.7 mV (n = 24). Inset: Response to hyperpolarizing and depolarizing current injections displaying stereotypic IN firing.(G) Minimum light power density (mW/mm2) necessary to trigger one spike in PNs (n = 33) and INs (n = 11). Significantly higher power was necessary to reach spike threshold in PNs (∗∗∗∗p < 0.0001).(H) The IPSP induced by a single light pulse was blocked by glutamatergic antagonists NBQX (10 μm)/APV (100 μm), suggesting it was mediated by FFI due to activation of BA INs (n = 5).(I) The early IPSP was blocked by the GABAA receptor antagonist SR95531 (10 μm, n = 5).(J) The late IPSP was blocked by the GABAB receptor antagonist CGP54626 (5 μm, n = 26). Co-application of SR95531 and CGP54626 abolished IPSPs and increased the duration of the EPSP. All data from whole-cell recordings shown are three superimposed (gray) and average traces (black). Data are presented as means ± SEM.
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fig3: Activation of Hippocampal Inputs Provides FFI of BA PNs(A) Ex vivo cell-attached recording from a representative PN in response to single light pulses (20 superimposed sweeps, top; singularly represented in raster plot, bottom). Red circles denote spike negative peak.(B) Mean probability of firing of PNs (bins = 10 ms, black: mean, red: SEM; n = 24).(C) Whole-cell recording of the same cell as in (A) showing that the light pulse induced a PSP composed of an EPSP followed by a biphasic IPSP. On average, the peak amplitudes of the EPSP, early IPSP, and late IPSP were 8.9 ± 1 mV, 4.1 ± 0.8 mV, and 2.7 ± 0.6 mV (n = 24), respectively. Inset: Response to hyperpolarizing and depolarizing current injections showing stereotypic PN firing.(D) Cell-attached recording from a representative IN in response to a single light pulse (20 superimposed sweeps, top; singularly represented in raster plot, bottom). Blue circles denote spike negative peak.(E) Mean probability of firing of INs (bin = 10 ms, black: mean, red: SEM; n = 11).(F) Whole-cell recording of the same cell as in (D) showing that the light stimulation evoked a monophasic EPSP. On average, the peak amplitude of the EPSP was 8.1 ± 0.7 mV (n = 24). Inset: Response to hyperpolarizing and depolarizing current injections displaying stereotypic IN firing.(G) Minimum light power density (mW/mm2) necessary to trigger one spike in PNs (n = 33) and INs (n = 11). Significantly higher power was necessary to reach spike threshold in PNs (∗∗∗∗p < 0.0001).(H) The IPSP induced by a single light pulse was blocked by glutamatergic antagonists NBQX (10 μm)/APV (100 μm), suggesting it was mediated by FFI due to activation of BA INs (n = 5).(I) The early IPSP was blocked by the GABAA receptor antagonist SR95531 (10 μm, n = 5).(J) The late IPSP was blocked by the GABAB receptor antagonist CGP54626 (5 μm, n = 26). Co-application of SR95531 and CGP54626 abolished IPSPs and increased the duration of the EPSP. All data from whole-cell recordings shown are three superimposed (gray) and average traces (black). Data are presented as means ± SEM.

Mentions: Because vCA1 pyramidal cells are glutamatergic, we hypothesized that the inhibition of PNs was due to the disynaptic activation of feedforward INs, while the monosynaptic excitation of PNs would remain subthreshold. To test this hypothesis, we optogenetically dissected the BA circuit activated by vCA1 HPC ex vivo. We prepared acute brain slices 3 to 4 weeks after the ChR2 injection and recorded single BA neurons in cell attached mode (see Supplemental Experimental Procedures). This configuration did not alter the intracellular milieu of the recorded cell and mimicked our extracellular in vivo conditions. PNs and INs could be distinguished according to their soma size (diameter ≥ 20 μm for PNs, < 15 μm for INs). After cell-attached recordings, 8/40 PNs and 6/18 INs were re-patched in whole-cell mode to confirm their identity. Optical stimulations were delivered through the microscope objective to excite vCA1 axons within an area of ∼200 μm diameter around the soma of the recorded neurons. We observed that the power of a single light pulse stimulation had to be significantly higher (p < 0.0001) to trigger one action potential in PNs (9.5 ± 0.3 mW/mm2, n = 33) compared to INs (2.5 ± 0.2 mW/mm2, n = 11) (Figure 3).


Hippocampal Theta Input to the Amygdala Shapes Feedforward Inhibition to Gate Heterosynaptic Plasticity.

Bazelot M, Bocchio M, Kasugai Y, Fischer D, Dodson PD, Ferraguti F, Capogna M - Neuron (2015)

Activation of Hippocampal Inputs Provides FFI of BA PNs(A) Ex vivo cell-attached recording from a representative PN in response to single light pulses (20 superimposed sweeps, top; singularly represented in raster plot, bottom). Red circles denote spike negative peak.(B) Mean probability of firing of PNs (bins = 10 ms, black: mean, red: SEM; n = 24).(C) Whole-cell recording of the same cell as in (A) showing that the light pulse induced a PSP composed of an EPSP followed by a biphasic IPSP. On average, the peak amplitudes of the EPSP, early IPSP, and late IPSP were 8.9 ± 1 mV, 4.1 ± 0.8 mV, and 2.7 ± 0.6 mV (n = 24), respectively. Inset: Response to hyperpolarizing and depolarizing current injections showing stereotypic PN firing.(D) Cell-attached recording from a representative IN in response to a single light pulse (20 superimposed sweeps, top; singularly represented in raster plot, bottom). Blue circles denote spike negative peak.(E) Mean probability of firing of INs (bin = 10 ms, black: mean, red: SEM; n = 11).(F) Whole-cell recording of the same cell as in (D) showing that the light stimulation evoked a monophasic EPSP. On average, the peak amplitude of the EPSP was 8.1 ± 0.7 mV (n = 24). Inset: Response to hyperpolarizing and depolarizing current injections displaying stereotypic IN firing.(G) Minimum light power density (mW/mm2) necessary to trigger one spike in PNs (n = 33) and INs (n = 11). Significantly higher power was necessary to reach spike threshold in PNs (∗∗∗∗p < 0.0001).(H) The IPSP induced by a single light pulse was blocked by glutamatergic antagonists NBQX (10 μm)/APV (100 μm), suggesting it was mediated by FFI due to activation of BA INs (n = 5).(I) The early IPSP was blocked by the GABAA receptor antagonist SR95531 (10 μm, n = 5).(J) The late IPSP was blocked by the GABAB receptor antagonist CGP54626 (5 μm, n = 26). Co-application of SR95531 and CGP54626 abolished IPSPs and increased the duration of the EPSP. All data from whole-cell recordings shown are three superimposed (gray) and average traces (black). Data are presented as means ± SEM.
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fig3: Activation of Hippocampal Inputs Provides FFI of BA PNs(A) Ex vivo cell-attached recording from a representative PN in response to single light pulses (20 superimposed sweeps, top; singularly represented in raster plot, bottom). Red circles denote spike negative peak.(B) Mean probability of firing of PNs (bins = 10 ms, black: mean, red: SEM; n = 24).(C) Whole-cell recording of the same cell as in (A) showing that the light pulse induced a PSP composed of an EPSP followed by a biphasic IPSP. On average, the peak amplitudes of the EPSP, early IPSP, and late IPSP were 8.9 ± 1 mV, 4.1 ± 0.8 mV, and 2.7 ± 0.6 mV (n = 24), respectively. Inset: Response to hyperpolarizing and depolarizing current injections showing stereotypic PN firing.(D) Cell-attached recording from a representative IN in response to a single light pulse (20 superimposed sweeps, top; singularly represented in raster plot, bottom). Blue circles denote spike negative peak.(E) Mean probability of firing of INs (bin = 10 ms, black: mean, red: SEM; n = 11).(F) Whole-cell recording of the same cell as in (D) showing that the light stimulation evoked a monophasic EPSP. On average, the peak amplitude of the EPSP was 8.1 ± 0.7 mV (n = 24). Inset: Response to hyperpolarizing and depolarizing current injections displaying stereotypic IN firing.(G) Minimum light power density (mW/mm2) necessary to trigger one spike in PNs (n = 33) and INs (n = 11). Significantly higher power was necessary to reach spike threshold in PNs (∗∗∗∗p < 0.0001).(H) The IPSP induced by a single light pulse was blocked by glutamatergic antagonists NBQX (10 μm)/APV (100 μm), suggesting it was mediated by FFI due to activation of BA INs (n = 5).(I) The early IPSP was blocked by the GABAA receptor antagonist SR95531 (10 μm, n = 5).(J) The late IPSP was blocked by the GABAB receptor antagonist CGP54626 (5 μm, n = 26). Co-application of SR95531 and CGP54626 abolished IPSPs and increased the duration of the EPSP. All data from whole-cell recordings shown are three superimposed (gray) and average traces (black). Data are presented as means ± SEM.
Mentions: Because vCA1 pyramidal cells are glutamatergic, we hypothesized that the inhibition of PNs was due to the disynaptic activation of feedforward INs, while the monosynaptic excitation of PNs would remain subthreshold. To test this hypothesis, we optogenetically dissected the BA circuit activated by vCA1 HPC ex vivo. We prepared acute brain slices 3 to 4 weeks after the ChR2 injection and recorded single BA neurons in cell attached mode (see Supplemental Experimental Procedures). This configuration did not alter the intracellular milieu of the recorded cell and mimicked our extracellular in vivo conditions. PNs and INs could be distinguished according to their soma size (diameter ≥ 20 μm for PNs, < 15 μm for INs). After cell-attached recordings, 8/40 PNs and 6/18 INs were re-patched in whole-cell mode to confirm their identity. Optical stimulations were delivered through the microscope objective to excite vCA1 axons within an area of ∼200 μm diameter around the soma of the recorded neurons. We observed that the power of a single light pulse stimulation had to be significantly higher (p < 0.0001) to trigger one action potential in PNs (9.5 ± 0.3 mW/mm2, n = 33) compared to INs (2.5 ± 0.2 mW/mm2, n = 11) (Figure 3).

Bottom Line: These effects are mediated by GABAB receptors and change in the Cl(-) driving force.Hence, feedforward inhibition, known to enforce temporal fidelity of excitatory inputs, dominates hippocampus-amygdala interactions to gate heterosynaptic plasticity.VIDEO ABSTRACT.

View Article: PubMed Central - PubMed

Affiliation: MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3TH, UK.

Show MeSH
Related in: MedlinePlus