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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.


Regulation of Schaffer collateral pathway LTP by theta-burst stimulation in oriens-alveus. A. Diagram of experimental arrangement of extracellular recording and stimulation electrodes, and targeted CA1 pathways and cells. P, Pyramidal cell; I, inhibitory interneuron; SC, Schaffer collateral pathway; Rec, recording electrode; Alv, alveus; Or, stratum oriens; Pyr, stratum pyramidale; Rad, stratum radiatum; L-M, stratum lacunosum/moleculare. Arrowheads and bars refer to excitatory and inhibitory synapses, respectively. B–D, Time plots of Schaffer collateral fEPSP slope from individual representative slices from SOM-IRES-Cre;ArChR3/GFP mice showing LTP induced by HFS in stratum radiatum (B), enhanced LTP when HFS induction was preceded by a conditioning TBS in stratum oriens-alveus 30 min earlier (C), and no effect of TBS alone (D). Insets (B, C) are average fEPSPs (of 30 individual traces) during baseline, pre-HFS, and 30 min post-HFS. Scale bars: 0.5 mV, 5 ms. E, Summary fEPSP slope time plots for all slices, showing larger magnitude of HFS-induced LTP when preceded by TBS in stratum oriens-alveus. F, Summary bar graph showing increased HFS-induced LTP of fEPSP slope at 30 min postinduction after a conditioning TBS in oriens-alveus (TBS; HFS) relative to control without TBS (no TBS; HFS, ANOVA, **p = 0.0052), and no effects of TBS on fEPSPs in experiments without HFS.
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Figure 6: Regulation of Schaffer collateral pathway LTP by theta-burst stimulation in oriens-alveus. A. Diagram of experimental arrangement of extracellular recording and stimulation electrodes, and targeted CA1 pathways and cells. P, Pyramidal cell; I, inhibitory interneuron; SC, Schaffer collateral pathway; Rec, recording electrode; Alv, alveus; Or, stratum oriens; Pyr, stratum pyramidale; Rad, stratum radiatum; L-M, stratum lacunosum/moleculare. Arrowheads and bars refer to excitatory and inhibitory synapses, respectively. B–D, Time plots of Schaffer collateral fEPSP slope from individual representative slices from SOM-IRES-Cre;ArChR3/GFP mice showing LTP induced by HFS in stratum radiatum (B), enhanced LTP when HFS induction was preceded by a conditioning TBS in stratum oriens-alveus 30 min earlier (C), and no effect of TBS alone (D). Insets (B, C) are average fEPSPs (of 30 individual traces) during baseline, pre-HFS, and 30 min post-HFS. Scale bars: 0.5 mV, 5 ms. E, Summary fEPSP slope time plots for all slices, showing larger magnitude of HFS-induced LTP when preceded by TBS in stratum oriens-alveus. F, Summary bar graph showing increased HFS-induced LTP of fEPSP slope at 30 min postinduction after a conditioning TBS in oriens-alveus (TBS; HFS) relative to control without TBS (no TBS; HFS, ANOVA, **p = 0.0052), and no effects of TBS on fEPSPs in experiments without HFS.

Mentions: We then investigated whether LTP at SOM-INs synapses could produce a long-term regulation of LTP in the Schaffer collateral pathway using field recordings. In addition, for these experiments we used SOM-IRES-Cre;ArChR3/GFP mice for cell-specific expression in SOM-INs of archaerhodopsin-3 (ArCh3), an outward proton pump that causes hyperpolarization, so we could manipulate selectively SOM-IN excitability using optogenetics during field recording experiments. First, low-frequency Schaffer collateral stimulation was given in stratum radiatum to elicit CA1 fEPSPs during a baseline period (30 min; Fig. 6A,B). HFS (100 Hz, 1 s) of Schaffer collaterals was then applied, resulting in LTP of fEPSP slope (113.5 ± 4.7% of baseline at 30 min postinduction; n = 10, paired t test, p = 0.010s; Fig. 6B,E,F). In comparison, application of TBS in oriens-alveus resulted in enhancement of Schaffer collateral pathway LTP tested 30 min later (Fig. 6A,C). TBS in oriens-alveus did not affect Schaffer collateral evoked fEPSPs during the baseline period, indicating no effect on basal transmission (Fig. 6D). However, LTP induction in the Schaffer collateral pathway given 30 min after TBS in oriens-alveus, resulted in an increase in fEPSP slope (128.2 ± 3.5% of baseline, n = 11; paired t test, p = 0.0001t; Fig. 6C,E) that was greater than in the control condition without TBS (ANOVA, p = 0.0052u; Fig. 6F). The effect of TBS in oriens-alveus was tested also on Schaffer collateral pathway for the same time period but without subsequent LTP induction. TBS in oriens-alveus had no effect on Schaffer collateral fEPSPs recorded for a similar duration (102.2 ± 2.6% of baseline; n = 4; paired t test, p = 0.5794v; Fig. 6D–F). These results indicate that TBS in oriens-alveus does not affect basal transmission at CA3–CA1 synapses, but has a long-lasting effect to enhance LTP in the Schaffer collateral pathway.


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)

Regulation of Schaffer collateral pathway LTP by theta-burst stimulation in oriens-alveus. A. Diagram of experimental arrangement of extracellular recording and stimulation electrodes, and targeted CA1 pathways and cells. P, Pyramidal cell; I, inhibitory interneuron; SC, Schaffer collateral pathway; Rec, recording electrode; Alv, alveus; Or, stratum oriens; Pyr, stratum pyramidale; Rad, stratum radiatum; L-M, stratum lacunosum/moleculare. Arrowheads and bars refer to excitatory and inhibitory synapses, respectively. B–D, Time plots of Schaffer collateral fEPSP slope from individual representative slices from SOM-IRES-Cre;ArChR3/GFP mice showing LTP induced by HFS in stratum radiatum (B), enhanced LTP when HFS induction was preceded by a conditioning TBS in stratum oriens-alveus 30 min earlier (C), and no effect of TBS alone (D). Insets (B, C) are average fEPSPs (of 30 individual traces) during baseline, pre-HFS, and 30 min post-HFS. Scale bars: 0.5 mV, 5 ms. E, Summary fEPSP slope time plots for all slices, showing larger magnitude of HFS-induced LTP when preceded by TBS in stratum oriens-alveus. F, Summary bar graph showing increased HFS-induced LTP of fEPSP slope at 30 min postinduction after a conditioning TBS in oriens-alveus (TBS; HFS) relative to control without TBS (no TBS; HFS, ANOVA, **p = 0.0052), and no effects of TBS on fEPSPs in experiments without HFS.
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Related In: Results  -  Collection

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Show All Figures
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Figure 6: Regulation of Schaffer collateral pathway LTP by theta-burst stimulation in oriens-alveus. A. Diagram of experimental arrangement of extracellular recording and stimulation electrodes, and targeted CA1 pathways and cells. P, Pyramidal cell; I, inhibitory interneuron; SC, Schaffer collateral pathway; Rec, recording electrode; Alv, alveus; Or, stratum oriens; Pyr, stratum pyramidale; Rad, stratum radiatum; L-M, stratum lacunosum/moleculare. Arrowheads and bars refer to excitatory and inhibitory synapses, respectively. B–D, Time plots of Schaffer collateral fEPSP slope from individual representative slices from SOM-IRES-Cre;ArChR3/GFP mice showing LTP induced by HFS in stratum radiatum (B), enhanced LTP when HFS induction was preceded by a conditioning TBS in stratum oriens-alveus 30 min earlier (C), and no effect of TBS alone (D). Insets (B, C) are average fEPSPs (of 30 individual traces) during baseline, pre-HFS, and 30 min post-HFS. Scale bars: 0.5 mV, 5 ms. E, Summary fEPSP slope time plots for all slices, showing larger magnitude of HFS-induced LTP when preceded by TBS in stratum oriens-alveus. F, Summary bar graph showing increased HFS-induced LTP of fEPSP slope at 30 min postinduction after a conditioning TBS in oriens-alveus (TBS; HFS) relative to control without TBS (no TBS; HFS, ANOVA, **p = 0.0052), and no effects of TBS on fEPSPs in experiments without HFS.
Mentions: We then investigated whether LTP at SOM-INs synapses could produce a long-term regulation of LTP in the Schaffer collateral pathway using field recordings. In addition, for these experiments we used SOM-IRES-Cre;ArChR3/GFP mice for cell-specific expression in SOM-INs of archaerhodopsin-3 (ArCh3), an outward proton pump that causes hyperpolarization, so we could manipulate selectively SOM-IN excitability using optogenetics during field recording experiments. First, low-frequency Schaffer collateral stimulation was given in stratum radiatum to elicit CA1 fEPSPs during a baseline period (30 min; Fig. 6A,B). HFS (100 Hz, 1 s) of Schaffer collaterals was then applied, resulting in LTP of fEPSP slope (113.5 ± 4.7% of baseline at 30 min postinduction; n = 10, paired t test, p = 0.010s; Fig. 6B,E,F). In comparison, application of TBS in oriens-alveus resulted in enhancement of Schaffer collateral pathway LTP tested 30 min later (Fig. 6A,C). TBS in oriens-alveus did not affect Schaffer collateral evoked fEPSPs during the baseline period, indicating no effect on basal transmission (Fig. 6D). However, LTP induction in the Schaffer collateral pathway given 30 min after TBS in oriens-alveus, resulted in an increase in fEPSP slope (128.2 ± 3.5% of baseline, n = 11; paired t test, p = 0.0001t; Fig. 6C,E) that was greater than in the control condition without TBS (ANOVA, p = 0.0052u; Fig. 6F). The effect of TBS in oriens-alveus was tested also on Schaffer collateral pathway for the same time period but without subsequent LTP induction. TBS in oriens-alveus had no effect on Schaffer collateral fEPSPs recorded for a similar duration (102.2 ± 2.6% of baseline; n = 4; paired t test, p = 0.5794v; Fig. 6D–F). These results indicate that TBS in oriens-alveus does not affect basal transmission at CA3–CA1 synapses, but has a long-lasting effect to enhance LTP in the Schaffer collateral pathway.

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.