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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

mGluR1a-dependent Hebbian LTP at excitatory synapses onto CA1 EYFP-labeled SOM-INs. A–C, Diagrams (top, left) showing the stimulation pairing protocol for LTP induction (A; theta-burst stimulation paired with postsynaptic depolarization; TBS + Depo), the control stimulation protocols (B; TBS or postsynaptic depolarization alone) and the stimulation pairing protocol in the presence of 40 μm LY367385, an mGluR1a antagonist (C; TBS + Depo in LY). EPSC amplitude time plots (bottom, left) from representative CA1 EYFP-labeled SOM-INs showing increase in EPSC amplitude after the pairing protocol (A) but not after control stimulation (B; TBS alone in this particular example) nor in the presence of LY367385 (C). Twenty consecutive EPSC traces from respective cells from baseline period (top, right) and 30 min poststimulation (middle, right). Scale bars: 20 pA, 5 ms. Superimposed average traces (of 100 individual events, including failures; bottom, right; scale bars: 5 pA, 5 ms) illustrating the increase in response after the pairing protocol (A) but not control stimulation (B) nor in the presence of LY367385 (C). D, Summary bar graph for all cells, showing no change in EPSC amplitude (including failures) after control stimulation, increase 30 min after the pairing protocol, and no change after the pairing protocol in the presence of LY367385. ANOVA, **p = 0.0025. E–G, Summary time plots of EPSC measures (5 min bins) showing gradual development of LTP over time in all cells showing LTP after pairing (n = 9), but not in cells with control stimulation (n = 14) nor in cells with the pairing stimulation in the presence of LY367385 (n = 6). LTP was manifested as an increase in EPSC amplitude (including failures; E) and potency (F), and a decrease in failure rate (G). ANOVA and Dunnett’s multiple-comparison tests; *p < 0.05, **p < 0.01.
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Figure 3: mGluR1a-dependent Hebbian LTP at excitatory synapses onto CA1 EYFP-labeled SOM-INs. A–C, Diagrams (top, left) showing the stimulation pairing protocol for LTP induction (A; theta-burst stimulation paired with postsynaptic depolarization; TBS + Depo), the control stimulation protocols (B; TBS or postsynaptic depolarization alone) and the stimulation pairing protocol in the presence of 40 μm LY367385, an mGluR1a antagonist (C; TBS + Depo in LY). EPSC amplitude time plots (bottom, left) from representative CA1 EYFP-labeled SOM-INs showing increase in EPSC amplitude after the pairing protocol (A) but not after control stimulation (B; TBS alone in this particular example) nor in the presence of LY367385 (C). Twenty consecutive EPSC traces from respective cells from baseline period (top, right) and 30 min poststimulation (middle, right). Scale bars: 20 pA, 5 ms. Superimposed average traces (of 100 individual events, including failures; bottom, right; scale bars: 5 pA, 5 ms) illustrating the increase in response after the pairing protocol (A) but not control stimulation (B) nor in the presence of LY367385 (C). D, Summary bar graph for all cells, showing no change in EPSC amplitude (including failures) after control stimulation, increase 30 min after the pairing protocol, and no change after the pairing protocol in the presence of LY367385. ANOVA, **p = 0.0025. E–G, Summary time plots of EPSC measures (5 min bins) showing gradual development of LTP over time in all cells showing LTP after pairing (n = 9), but not in cells with control stimulation (n = 14) nor in cells with the pairing stimulation in the presence of LY367385 (n = 6). LTP was manifested as an increase in EPSC amplitude (including failures; E) and potency (F), and a decrease in failure rate (G). ANOVA and Dunnett’s multiple-comparison tests; *p < 0.05, **p < 0.01.

Mentions: Then we used whole-cell voltage-clamp recordings of EPSCs evoked by minimal stimulation of putative single-fibers to examine if excitatory synapses onto CA1 EYFP-labeled SOM-INs show Hebbian LTP. Pairing of theta-burst stimulation with postsynaptic depolarization (TBS + Depo) produced an increase in EPSC amplitude (average EPSC including failures) to 202.9 ± 31.3% of baseline at 30 min postinduction (paired t test, p = 0.0025a, n = 14; Fig. 3A,D). Control stimulation, consisting of theta-burst stimulation (n = 7) or depolarization (n = 7) alone, did not produce lasting changes in EPSC amplitude (96.0 ± 11.1% of baseline at 30 min postinduction for pooled controls; paired t test, p = 0.75b, n = 14; Fig. 3B,D).


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)

mGluR1a-dependent Hebbian LTP at excitatory synapses onto CA1 EYFP-labeled SOM-INs. A–C, Diagrams (top, left) showing the stimulation pairing protocol for LTP induction (A; theta-burst stimulation paired with postsynaptic depolarization; TBS + Depo), the control stimulation protocols (B; TBS or postsynaptic depolarization alone) and the stimulation pairing protocol in the presence of 40 μm LY367385, an mGluR1a antagonist (C; TBS + Depo in LY). EPSC amplitude time plots (bottom, left) from representative CA1 EYFP-labeled SOM-INs showing increase in EPSC amplitude after the pairing protocol (A) but not after control stimulation (B; TBS alone in this particular example) nor in the presence of LY367385 (C). Twenty consecutive EPSC traces from respective cells from baseline period (top, right) and 30 min poststimulation (middle, right). Scale bars: 20 pA, 5 ms. Superimposed average traces (of 100 individual events, including failures; bottom, right; scale bars: 5 pA, 5 ms) illustrating the increase in response after the pairing protocol (A) but not control stimulation (B) nor in the presence of LY367385 (C). D, Summary bar graph for all cells, showing no change in EPSC amplitude (including failures) after control stimulation, increase 30 min after the pairing protocol, and no change after the pairing protocol in the presence of LY367385. ANOVA, **p = 0.0025. E–G, Summary time plots of EPSC measures (5 min bins) showing gradual development of LTP over time in all cells showing LTP after pairing (n = 9), but not in cells with control stimulation (n = 14) nor in cells with the pairing stimulation in the presence of LY367385 (n = 6). LTP was manifested as an increase in EPSC amplitude (including failures; E) and potency (F), and a decrease in failure rate (G). ANOVA and Dunnett’s multiple-comparison tests; *p < 0.05, **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: mGluR1a-dependent Hebbian LTP at excitatory synapses onto CA1 EYFP-labeled SOM-INs. A–C, Diagrams (top, left) showing the stimulation pairing protocol for LTP induction (A; theta-burst stimulation paired with postsynaptic depolarization; TBS + Depo), the control stimulation protocols (B; TBS or postsynaptic depolarization alone) and the stimulation pairing protocol in the presence of 40 μm LY367385, an mGluR1a antagonist (C; TBS + Depo in LY). EPSC amplitude time plots (bottom, left) from representative CA1 EYFP-labeled SOM-INs showing increase in EPSC amplitude after the pairing protocol (A) but not after control stimulation (B; TBS alone in this particular example) nor in the presence of LY367385 (C). Twenty consecutive EPSC traces from respective cells from baseline period (top, right) and 30 min poststimulation (middle, right). Scale bars: 20 pA, 5 ms. Superimposed average traces (of 100 individual events, including failures; bottom, right; scale bars: 5 pA, 5 ms) illustrating the increase in response after the pairing protocol (A) but not control stimulation (B) nor in the presence of LY367385 (C). D, Summary bar graph for all cells, showing no change in EPSC amplitude (including failures) after control stimulation, increase 30 min after the pairing protocol, and no change after the pairing protocol in the presence of LY367385. ANOVA, **p = 0.0025. E–G, Summary time plots of EPSC measures (5 min bins) showing gradual development of LTP over time in all cells showing LTP after pairing (n = 9), but not in cells with control stimulation (n = 14) nor in cells with the pairing stimulation in the presence of LY367385 (n = 6). LTP was manifested as an increase in EPSC amplitude (including failures; E) and potency (F), and a decrease in failure rate (G). ANOVA and Dunnett’s multiple-comparison tests; *p < 0.05, **p < 0.01.
Mentions: Then we used whole-cell voltage-clamp recordings of EPSCs evoked by minimal stimulation of putative single-fibers to examine if excitatory synapses onto CA1 EYFP-labeled SOM-INs show Hebbian LTP. Pairing of theta-burst stimulation with postsynaptic depolarization (TBS + Depo) produced an increase in EPSC amplitude (average EPSC including failures) to 202.9 ± 31.3% of baseline at 30 min postinduction (paired t test, p = 0.0025a, n = 14; Fig. 3A,D). Control stimulation, consisting of theta-burst stimulation (n = 7) or depolarization (n = 7) alone, did not produce lasting changes in EPSC amplitude (96.0 ± 11.1% of baseline at 30 min postinduction for pooled controls; paired t test, p = 0.75b, n = 14; Fig. 3B,D).

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