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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 LTP in current-clamp recordings with intact glutamatergic and GABAergic transmission. A, B, Averaged EPSPs from 30 consecutive responses during the baseline period (top, left) and 30 min after TBS (top, right) in the absence (A) and presence (B) of LY367385 from representative EYFP-labeled SOM-INs. Firing patterns during TBS (bottom). Note the prolonged depolarization underlying each burst in control conditions (A), which is abolished in the presence of LY367385 (B). Scale bars: top, 2 mV, 50 ms; bottom, 20 mV, 200 ms. C, Bar graph showing the decreased number of APs elicited during the TBS protocol in the absence (n = 8) and presence (n = 5) of LY367385 (Student’s test). D, Summary time plot of EPSP amplitude (5 min bins) for all cells, showing the gradual development of LTP over time, which is blocked in the presence of LY367385 (rmANOVA, p = 0.001, and Dunnett’s multiple-comparison tests from baseline). *p < 0.05, **p < 0.01, ***p < 0.001.
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Figure 5: mGluR1a-dependent LTP in current-clamp recordings with intact glutamatergic and GABAergic transmission. A, B, Averaged EPSPs from 30 consecutive responses during the baseline period (top, left) and 30 min after TBS (top, right) in the absence (A) and presence (B) of LY367385 from representative EYFP-labeled SOM-INs. Firing patterns during TBS (bottom). Note the prolonged depolarization underlying each burst in control conditions (A), which is abolished in the presence of LY367385 (B). Scale bars: top, 2 mV, 50 ms; bottom, 20 mV, 200 ms. C, Bar graph showing the decreased number of APs elicited during the TBS protocol in the absence (n = 8) and presence (n = 5) of LY367385 (Student’s test). D, Summary time plot of EPSP amplitude (5 min bins) for all cells, showing the gradual development of LTP over time, which is blocked in the presence of LY367385 (rmANOVA, p = 0.001, and Dunnett’s multiple-comparison tests from baseline). *p < 0.05, **p < 0.01, ***p < 0.001.

Mentions: Hippocampal slices were prepared from 4- to 8-week-old SOM-IRES-Cre;Ai3-EYFP mice and 6- to 8-week-old PV-Cre;Ai3-EYFP mice. Animals were anesthetized with isoflurane and the brain was rapidly excised and placed in ice-cold sucrose-based cutting solution saturated with 95% O2 and 5% CO2 containing the following (in mm): 87 NaCl, 2.5 KCl, 1.25 NaH2PO4, 7 MgSO4, 0.5 CaCl2, 25 NaHCO3, 25 glucose, 11.6 ascorbic acid, 3.1 pyruvic acid, and 75 sucrose, pH 7.4, and 295 mOsmol. A block of tissue containing the hippocampus was prepared and transverse hippocampal slices (300 μm thick) were cut on a vibratome (Leica VT1000S). Slices were transferred to oxygenated artificial CSF (ACSF) at room temperature containing the following (in mm): 124 NaCl, 2.5 KCl, 1.25 NaH2PO4, 4 MgSO4, 4 CaCl2, 26 NaHCO3, and 10 glucose, pH 7.3–7.4, and 295–305 mOsmol, allowed to recover for at least 1 h, and transferred for experiments to a submersion chamber perfused (2 ml/min) with ACSF at 31 ± 0.5°C. Prior to recordings, CA1 and CA3 regions were isolated by a surgical cut. EYFP-expressing CA1 interneurons were identified using an upright microscope (Nikon Eclipse, E600FN), equipped with a water-immersion long-working distance objective (40×, Nomarski Optics), epifluorescence and an infrared video camera. Whole-cell voltage-clamp recordings were obtained using borosilicate glass pipettes (3-6 MΩ) filled with intracellular solution containing the following (in mm): 130 CsMeSO3, 5 NaCl, 1 MgCl2, 10 phosphocreatine, 10 HEPES, 2 ATP-Tris, 0.4 GTP-Tris, 0.1 spermine, 2 QX314, and 0.1% biocytin, pH 7.2–7.3, and 275–285 mOsmol. For whole-cell current-clamp recordings of intrinsic properties, the intracellular solution contained the following (in mm): 150 K-gluconate, 3 MgCl2, 0.5 EGTA, 10 HEPES, 2 MgATP, 0.3 NaGTP, and 0.1% biocytin, pH 7.4, and 300 mOsmol (Fig. 2). For recordings of synaptic potentials, the intracellular solution contained the following (in mm): 120 KMeSO4, 10 KCl, 0.5 EGTA, 10 HEPES, 2.5 MgATP, 0.3 NaGTP, 10 Na2-phosphocreatine, 0.1 spermine, and 0.1% biocytin, pH 7.3–7.4, and 280 ± 5 mOsmol (Fig. 5). Data was acquired using a Multiclamp 700B amplifier (Molecular Devices) and digitized using Digidata 1440A and pClamp 10 (Molecular Devices). Recordings were low-pass filtered at 2 kHz and digitized at 20 kHz. Series resistance was regularly monitored during experiments and data were included only if the holding current and series resistance were stable.


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 LTP in current-clamp recordings with intact glutamatergic and GABAergic transmission. A, B, Averaged EPSPs from 30 consecutive responses during the baseline period (top, left) and 30 min after TBS (top, right) in the absence (A) and presence (B) of LY367385 from representative EYFP-labeled SOM-INs. Firing patterns during TBS (bottom). Note the prolonged depolarization underlying each burst in control conditions (A), which is abolished in the presence of LY367385 (B). Scale bars: top, 2 mV, 50 ms; bottom, 20 mV, 200 ms. C, Bar graph showing the decreased number of APs elicited during the TBS protocol in the absence (n = 8) and presence (n = 5) of LY367385 (Student’s test). D, Summary time plot of EPSP amplitude (5 min bins) for all cells, showing the gradual development of LTP over time, which is blocked in the presence of LY367385 (rmANOVA, p = 0.001, and Dunnett’s multiple-comparison tests from baseline). *p < 0.05, **p < 0.01, ***p < 0.001.
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Figure 5: mGluR1a-dependent LTP in current-clamp recordings with intact glutamatergic and GABAergic transmission. A, B, Averaged EPSPs from 30 consecutive responses during the baseline period (top, left) and 30 min after TBS (top, right) in the absence (A) and presence (B) of LY367385 from representative EYFP-labeled SOM-INs. Firing patterns during TBS (bottom). Note the prolonged depolarization underlying each burst in control conditions (A), which is abolished in the presence of LY367385 (B). Scale bars: top, 2 mV, 50 ms; bottom, 20 mV, 200 ms. C, Bar graph showing the decreased number of APs elicited during the TBS protocol in the absence (n = 8) and presence (n = 5) of LY367385 (Student’s test). D, Summary time plot of EPSP amplitude (5 min bins) for all cells, showing the gradual development of LTP over time, which is blocked in the presence of LY367385 (rmANOVA, p = 0.001, and Dunnett’s multiple-comparison tests from baseline). *p < 0.05, **p < 0.01, ***p < 0.001.
Mentions: Hippocampal slices were prepared from 4- to 8-week-old SOM-IRES-Cre;Ai3-EYFP mice and 6- to 8-week-old PV-Cre;Ai3-EYFP mice. Animals were anesthetized with isoflurane and the brain was rapidly excised and placed in ice-cold sucrose-based cutting solution saturated with 95% O2 and 5% CO2 containing the following (in mm): 87 NaCl, 2.5 KCl, 1.25 NaH2PO4, 7 MgSO4, 0.5 CaCl2, 25 NaHCO3, 25 glucose, 11.6 ascorbic acid, 3.1 pyruvic acid, and 75 sucrose, pH 7.4, and 295 mOsmol. A block of tissue containing the hippocampus was prepared and transverse hippocampal slices (300 μm thick) were cut on a vibratome (Leica VT1000S). Slices were transferred to oxygenated artificial CSF (ACSF) at room temperature containing the following (in mm): 124 NaCl, 2.5 KCl, 1.25 NaH2PO4, 4 MgSO4, 4 CaCl2, 26 NaHCO3, and 10 glucose, pH 7.3–7.4, and 295–305 mOsmol, allowed to recover for at least 1 h, and transferred for experiments to a submersion chamber perfused (2 ml/min) with ACSF at 31 ± 0.5°C. Prior to recordings, CA1 and CA3 regions were isolated by a surgical cut. EYFP-expressing CA1 interneurons were identified using an upright microscope (Nikon Eclipse, E600FN), equipped with a water-immersion long-working distance objective (40×, Nomarski Optics), epifluorescence and an infrared video camera. Whole-cell voltage-clamp recordings were obtained using borosilicate glass pipettes (3-6 MΩ) filled with intracellular solution containing the following (in mm): 130 CsMeSO3, 5 NaCl, 1 MgCl2, 10 phosphocreatine, 10 HEPES, 2 ATP-Tris, 0.4 GTP-Tris, 0.1 spermine, 2 QX314, and 0.1% biocytin, pH 7.2–7.3, and 275–285 mOsmol. For whole-cell current-clamp recordings of intrinsic properties, the intracellular solution contained the following (in mm): 150 K-gluconate, 3 MgCl2, 0.5 EGTA, 10 HEPES, 2 MgATP, 0.3 NaGTP, and 0.1% biocytin, pH 7.4, and 300 mOsmol (Fig. 2). For recordings of synaptic potentials, the intracellular solution contained the following (in mm): 120 KMeSO4, 10 KCl, 0.5 EGTA, 10 HEPES, 2.5 MgATP, 0.3 NaGTP, 10 Na2-phosphocreatine, 0.1 spermine, and 0.1% biocytin, pH 7.3–7.4, and 280 ± 5 mOsmol (Fig. 5). Data was acquired using a Multiclamp 700B amplifier (Molecular Devices) and digitized using Digidata 1440A and pClamp 10 (Molecular Devices). Recordings were low-pass filtered at 2 kHz and digitized at 20 kHz. Series resistance was regularly monitored during experiments and data were included only if the holding current and series resistance were stable.

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