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Metaplastic Regulation of CA1 Schaffer Collateral Pathway Plasticity by Hebbian MGluR1a-Mediated Plasticity at Excitatory Synapses onto Somatostatin-Expressing Interneurons(1,2,3).

Vasuta C, Artinian J, Laplante I, Hébert-Seropian S, Elayoubi K, Lacaille JC - eNeuro (2015)

Bottom Line: This effect was prevented by light-induced hyperpolarization of SOM-INs during TBS, or by application of the mGluR1a antagonist LY367385, indicating a necessity for mGluR1a and SOM-INs activation.These results uncover that SOM-INs perform an activity-dependent metaplastic control on hippocampal CA1 microcircuits in a cell-specific fashion.Our findings provide new insights on the contribution of interneuron synaptic plasticity in the regulation of the hippocampal network activity and mnemonic processes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Groupe de Recherche sur le Système Nerveux Central and Department of Neuroscience, Faculty of Medicine, Université de Montréal , Montreal, Quebec H3T 1J4, Canada.

ABSTRACT
Cortical GABAergic interneurons represent a highly diverse neuronal type that regulates neural network activity. In particular, interneurons in the hippocampal CA1 oriens/alveus (O/A-INs) area provide feedback dendritic inhibition to local pyramidal cells and express somatostatin (SOM). Under relevant afferent stimulation patterns, they undergo long-term potentiation (LTP) of their excitatory synaptic inputs through multiple induction and expression mechanisms. However, the cell-type specificity of these different forms of LTP and their specific contribution to the dynamic regulation of the CA1 network remain unclear. Here we recorded from SOM-expressing interneurons (SOM-INs) in the O/A region from SOM-Cre-Ai3 transgenic mice in whole-cell patch-clamp. Results indicate that, like in anatomically identified O/A-INs, theta-burst stimulation (TBS) induced a Hebbian form of LTP dependent on metabotropic glutamate receptor type 1a (mGluR1a) in SOM-INs, but not in parvalbumin-expressing interneurons, another mainly nonoverlapping interneuron subtype in CA1. In addition, we demonstrated using field recordings from transgenic mice expressing archaerhodopsin 3 selectively in SOM-INs, that a prior conditioning TBS in O/A, to induce mGluR1a-dependent LTP in SOM-INs, upregulated LTP in the Schaffer collateral pathway of pyramidal cells. This effect was prevented by light-induced hyperpolarization of SOM-INs during TBS, or by application of the mGluR1a antagonist LY367385, indicating a necessity for mGluR1a and SOM-INs activation. These results uncover that SOM-INs perform an activity-dependent metaplastic control on hippocampal CA1 microcircuits in a cell-specific fashion. Our findings provide new insights on the contribution of interneuron synaptic plasticity in the regulation of the hippocampal network activity and mnemonic processes.

No MeSH data available.


Related in: MedlinePlus

Absence of LTP at the excitatory synapses onto CA1 EYFP-labeled PV-INs. A, B, Diagrams (top) showing the pairing protocol for LTP induction (A; theta-burst stimulation paired with postsynaptic depolarization; TBS + Depo) and the control stimulation protocols (B; TBS or postsynaptic depolarization alone). EPSC amplitude time plots (bottom, left) from representative CA1 EYFP-labeled PV-INs showing no increase in EPSC amplitude after the pairing protocol (A) nor after control stimulation (B; TBS alone in this example). Twenty individual traces from respective cells during baseline period (top, right) and 30 min poststimulation (middle, right). Scale bars: 10 pA, 5 ms. Superimposed average traces (of 100 individual events, including failures; bottom, right; scale bars: 5 pA, 5 ms) illustrating the failure to increase responses after the pairing protocol (A) or control stimulation (B). C, Summary time plots of EPSC amplitude (5 min bins) for all cells showing no change over time in EPSC amplitude (including failures) after the pairing protocol (n = 6) or control stimulation (n = 6). ANOVA and Dunnett’s multiple-comparison tests, p > 0.05. D, Summary bar graphs for all cells showing lack of LTP in PV-INs after the pairing protocol (n = 6; ANOVA, p = 0.205) or control stimulation (n = 6; p = 0.633).
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Figure 4: Absence of LTP at the excitatory synapses onto CA1 EYFP-labeled PV-INs. A, B, Diagrams (top) showing the pairing protocol for LTP induction (A; theta-burst stimulation paired with postsynaptic depolarization; TBS + Depo) and the control stimulation protocols (B; TBS or postsynaptic depolarization alone). EPSC amplitude time plots (bottom, left) from representative CA1 EYFP-labeled PV-INs showing no increase in EPSC amplitude after the pairing protocol (A) nor after control stimulation (B; TBS alone in this example). Twenty individual traces from respective cells during baseline period (top, right) and 30 min poststimulation (middle, right). Scale bars: 10 pA, 5 ms. Superimposed average traces (of 100 individual events, including failures; bottom, right; scale bars: 5 pA, 5 ms) illustrating the failure to increase responses after the pairing protocol (A) or control stimulation (B). C, Summary time plots of EPSC amplitude (5 min bins) for all cells showing no change over time in EPSC amplitude (including failures) after the pairing protocol (n = 6) or control stimulation (n = 6). ANOVA and Dunnett’s multiple-comparison tests, p > 0.05. D, Summary bar graphs for all cells showing lack of LTP in PV-INs after the pairing protocol (n = 6; ANOVA, p = 0.205) or control stimulation (n = 6; p = 0.633).

Mentions: PV-INs are another distinct subpopulation of interneurons with perisomatic projections to pyramidal cells (Freund and Buzsáki, 1996). Next we used a similar approach but with whole-cell recordings from CA1 EYFP-labeled PV-INs obtained from PV-Cre;Ai3-EYFP mice to determine whether Hebbian mGluR1a-mediated LTP was also present in this interneuron type or whether it was cell-type-specific. Pairing of theta-burst stimulation with postsynaptic depolarization (TBS + Depo; Fig. 4A,C) failed to produce gradual changes in EPSC amplitude in CA1 EYFP-labeled PV-INs over 30 min postinduction (average EPSC including failures: 67.8 ± 15.4% of baseline at 30 min postinduction; paired t test, p = 0.2057m; n = 6; Fig. 4D). Similarly, control stimulation, consisting of theta-burst stimulation (n = 4) or depolarization (n = 2) alone (Fig. 4B,C), did not produce lasting changes in EPSC amplitude (119.0 ± 33.6% of baseline at 30 min postinduction for pooled controls; paired t test, p = 0.6333n; n = 6; Fig. 4D). These results reveal that Hebbian mGluR1a-mediated LTP is absent from afferent inputs to another large population of CA1 interneurons, the PV-INs, and thus shows cell-type specificity for SOM-INs synapses.


Metaplastic Regulation of CA1 Schaffer Collateral Pathway Plasticity by Hebbian MGluR1a-Mediated Plasticity at Excitatory Synapses onto Somatostatin-Expressing Interneurons(1,2,3).

Vasuta C, Artinian J, Laplante I, Hébert-Seropian S, Elayoubi K, Lacaille JC - eNeuro (2015)

Absence of LTP at the excitatory synapses onto CA1 EYFP-labeled PV-INs. A, B, Diagrams (top) showing the pairing protocol for LTP induction (A; theta-burst stimulation paired with postsynaptic depolarization; TBS + Depo) and the control stimulation protocols (B; TBS or postsynaptic depolarization alone). EPSC amplitude time plots (bottom, left) from representative CA1 EYFP-labeled PV-INs showing no increase in EPSC amplitude after the pairing protocol (A) nor after control stimulation (B; TBS alone in this example). Twenty individual traces from respective cells during baseline period (top, right) and 30 min poststimulation (middle, right). Scale bars: 10 pA, 5 ms. Superimposed average traces (of 100 individual events, including failures; bottom, right; scale bars: 5 pA, 5 ms) illustrating the failure to increase responses after the pairing protocol (A) or control stimulation (B). C, Summary time plots of EPSC amplitude (5 min bins) for all cells showing no change over time in EPSC amplitude (including failures) after the pairing protocol (n = 6) or control stimulation (n = 6). ANOVA and Dunnett’s multiple-comparison tests, p > 0.05. D, Summary bar graphs for all cells showing lack of LTP in PV-INs after the pairing protocol (n = 6; ANOVA, p = 0.205) or control stimulation (n = 6; p = 0.633).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4596015&req=5

Figure 4: Absence of LTP at the excitatory synapses onto CA1 EYFP-labeled PV-INs. A, B, Diagrams (top) showing the pairing protocol for LTP induction (A; theta-burst stimulation paired with postsynaptic depolarization; TBS + Depo) and the control stimulation protocols (B; TBS or postsynaptic depolarization alone). EPSC amplitude time plots (bottom, left) from representative CA1 EYFP-labeled PV-INs showing no increase in EPSC amplitude after the pairing protocol (A) nor after control stimulation (B; TBS alone in this example). Twenty individual traces from respective cells during baseline period (top, right) and 30 min poststimulation (middle, right). Scale bars: 10 pA, 5 ms. Superimposed average traces (of 100 individual events, including failures; bottom, right; scale bars: 5 pA, 5 ms) illustrating the failure to increase responses after the pairing protocol (A) or control stimulation (B). C, Summary time plots of EPSC amplitude (5 min bins) for all cells showing no change over time in EPSC amplitude (including failures) after the pairing protocol (n = 6) or control stimulation (n = 6). ANOVA and Dunnett’s multiple-comparison tests, p > 0.05. D, Summary bar graphs for all cells showing lack of LTP in PV-INs after the pairing protocol (n = 6; ANOVA, p = 0.205) or control stimulation (n = 6; p = 0.633).
Mentions: PV-INs are another distinct subpopulation of interneurons with perisomatic projections to pyramidal cells (Freund and Buzsáki, 1996). Next we used a similar approach but with whole-cell recordings from CA1 EYFP-labeled PV-INs obtained from PV-Cre;Ai3-EYFP mice to determine whether Hebbian mGluR1a-mediated LTP was also present in this interneuron type or whether it was cell-type-specific. Pairing of theta-burst stimulation with postsynaptic depolarization (TBS + Depo; Fig. 4A,C) failed to produce gradual changes in EPSC amplitude in CA1 EYFP-labeled PV-INs over 30 min postinduction (average EPSC including failures: 67.8 ± 15.4% of baseline at 30 min postinduction; paired t test, p = 0.2057m; n = 6; Fig. 4D). Similarly, control stimulation, consisting of theta-burst stimulation (n = 4) or depolarization (n = 2) alone (Fig. 4B,C), did not produce lasting changes in EPSC amplitude (119.0 ± 33.6% of baseline at 30 min postinduction for pooled controls; paired t test, p = 0.6333n; n = 6; Fig. 4D). These results reveal that Hebbian mGluR1a-mediated LTP is absent from afferent inputs to another large population of CA1 interneurons, the PV-INs, and thus shows cell-type specificity for SOM-INs synapses.

Bottom Line: This effect was prevented by light-induced hyperpolarization of SOM-INs during TBS, or by application of the mGluR1a antagonist LY367385, indicating a necessity for mGluR1a and SOM-INs activation.These results uncover that SOM-INs perform an activity-dependent metaplastic control on hippocampal CA1 microcircuits in a cell-specific fashion.Our findings provide new insights on the contribution of interneuron synaptic plasticity in the regulation of the hippocampal network activity and mnemonic processes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Groupe de Recherche sur le Système Nerveux Central and Department of Neuroscience, Faculty of Medicine, Université de Montréal , Montreal, Quebec H3T 1J4, Canada.

ABSTRACT
Cortical GABAergic interneurons represent a highly diverse neuronal type that regulates neural network activity. In particular, interneurons in the hippocampal CA1 oriens/alveus (O/A-INs) area provide feedback dendritic inhibition to local pyramidal cells and express somatostatin (SOM). Under relevant afferent stimulation patterns, they undergo long-term potentiation (LTP) of their excitatory synaptic inputs through multiple induction and expression mechanisms. However, the cell-type specificity of these different forms of LTP and their specific contribution to the dynamic regulation of the CA1 network remain unclear. Here we recorded from SOM-expressing interneurons (SOM-INs) in the O/A region from SOM-Cre-Ai3 transgenic mice in whole-cell patch-clamp. Results indicate that, like in anatomically identified O/A-INs, theta-burst stimulation (TBS) induced a Hebbian form of LTP dependent on metabotropic glutamate receptor type 1a (mGluR1a) in SOM-INs, but not in parvalbumin-expressing interneurons, another mainly nonoverlapping interneuron subtype in CA1. In addition, we demonstrated using field recordings from transgenic mice expressing archaerhodopsin 3 selectively in SOM-INs, that a prior conditioning TBS in O/A, to induce mGluR1a-dependent LTP in SOM-INs, upregulated LTP in the Schaffer collateral pathway of pyramidal cells. This effect was prevented by light-induced hyperpolarization of SOM-INs during TBS, or by application of the mGluR1a antagonist LY367385, indicating a necessity for mGluR1a and SOM-INs activation. These results uncover that SOM-INs perform an activity-dependent metaplastic control on hippocampal CA1 microcircuits in a cell-specific fashion. Our findings provide new insights on the contribution of interneuron synaptic plasticity in the regulation of the hippocampal network activity and mnemonic processes.

No MeSH data available.


Related in: MedlinePlus