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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.


Distribution of EYFP-labeled CA1 interneurons and specific colocalization with SOM and PV. A, B, Montage of fluorescence images showing the mostly nonoverlapping distribution of EYFP-labeled INs in the hippocampus from SOM-IRES-Cre;Ai3-EYFP (A) and PV-Cre;Ai3-EYFP (B) mice. Scale bars, 100 µm. In the CA1 region, EYFP-labeled INs of SOM-IRES-Cre;Ai3-EYFP mice are present mostly in the oriens and alveus regions, whereas EYFP-labeled INs of PV-Cre;Ai3-EYFP mice are found near or in the pyramidal cell layer. C, D, Representative examples of specific colocalization of EYFP-labeled INs (top, green) from SOM-IRES-Cre;Ai3-EYFP (C) and PV-Cre;Ai3-EYFP (D) mice with immunofluorescence for somatostatin (middle left, red) and parvalbumin (middle right, red), respectively. Merged images are shown at bottom. Scale bars, 10 µm. Nearly all CA1 EYFP-labeled INs from SOM-IRES-Cre;Ai3-EYFP mice colocalized with somatostatin but not parvalbumin (C). Conversely, mostly all CA1 EYFP-labeled INs from PV-Cre;Ai3-EYFP mice were immunopositive for parvalbumin but not somatostatin (D).
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Figure 1: Distribution of EYFP-labeled CA1 interneurons and specific colocalization with SOM and PV. A, B, Montage of fluorescence images showing the mostly nonoverlapping distribution of EYFP-labeled INs in the hippocampus from SOM-IRES-Cre;Ai3-EYFP (A) and PV-Cre;Ai3-EYFP (B) mice. Scale bars, 100 µm. In the CA1 region, EYFP-labeled INs of SOM-IRES-Cre;Ai3-EYFP mice are present mostly in the oriens and alveus regions, whereas EYFP-labeled INs of PV-Cre;Ai3-EYFP mice are found near or in the pyramidal cell layer. C, D, Representative examples of specific colocalization of EYFP-labeled INs (top, green) from SOM-IRES-Cre;Ai3-EYFP (C) and PV-Cre;Ai3-EYFP (D) mice with immunofluorescence for somatostatin (middle left, red) and parvalbumin (middle right, red), respectively. Merged images are shown at bottom. Scale bars, 10 µm. Nearly all CA1 EYFP-labeled INs from SOM-IRES-Cre;Ai3-EYFP mice colocalized with somatostatin but not parvalbumin (C). Conversely, mostly all CA1 EYFP-labeled INs from PV-Cre;Ai3-EYFP mice were immunopositive for parvalbumin but not somatostatin (D).

Mentions: SOM-INs or PV-INs were specifically labeled by breeding Ai3-EYFP reporter mice with SOM-IRES-Cre or PV-Cre mice, respectively. The distribution of EYFP-labelled SOM-INs and PV-INs interneurons was examined by fluorescence microscopy and their colocalization with somatostatin or parvalbumin was determined by immunofluorescence. Consistent with previous work (for review, see Freund and Buzsáki, 1996), the distribution of SOM-INs and PV-INs in the CA1 hippocampus was mostly nonoverlapping. EYFP-labeled SOM-IN somas were located mostly in stratum oriens and alveus of the CA1 and CA3 regions, as well as in the hilus of the dentate gyrus (Fig. 1A). EYFP-labeled PV-IN somas were mainly found in and around the pyramidal cell layer of CA1 and CA3 regions, and the granule cell layer of the dentate gyrus (Fig. 1B). We next verified the cell-specificity of the EYFP-labeling of CA1 interneurons by immunofluorescence. In SOM-IRES-Cre;Ai3-EYFP mice (Fig. 1C), 98.5% of EYFP-labeled interneurons in the CA1 region were immunopositive for somatostatin (n = 323 cells, 3 animals from 2 different litters), whereas only 6.9% of them were positive for parvalbumin (n = 354). In contrast in PV-Cre;Ai3-EYFP mice (Fig. 1D), 97.8% of EYFP-labeled CA1 interneurons were immunopositive for parvalbumin (n = 267 cells, 3 animals from 2 different litters), and only 10.7% were positive for somatostatin (n = 193 cells), thus confirming the specific labeling of mostly nonoverlapping CA1 populations of dendrite-projecting SOM-INs and perisomatic projecting PV-INs (Freund and Buzsáki, 1996; Tricoire et al., 2011) in the mice lines.


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)

Distribution of EYFP-labeled CA1 interneurons and specific colocalization with SOM and PV. A, B, Montage of fluorescence images showing the mostly nonoverlapping distribution of EYFP-labeled INs in the hippocampus from SOM-IRES-Cre;Ai3-EYFP (A) and PV-Cre;Ai3-EYFP (B) mice. Scale bars, 100 µm. In the CA1 region, EYFP-labeled INs of SOM-IRES-Cre;Ai3-EYFP mice are present mostly in the oriens and alveus regions, whereas EYFP-labeled INs of PV-Cre;Ai3-EYFP mice are found near or in the pyramidal cell layer. C, D, Representative examples of specific colocalization of EYFP-labeled INs (top, green) from SOM-IRES-Cre;Ai3-EYFP (C) and PV-Cre;Ai3-EYFP (D) mice with immunofluorescence for somatostatin (middle left, red) and parvalbumin (middle right, red), respectively. Merged images are shown at bottom. Scale bars, 10 µm. Nearly all CA1 EYFP-labeled INs from SOM-IRES-Cre;Ai3-EYFP mice colocalized with somatostatin but not parvalbumin (C). Conversely, mostly all CA1 EYFP-labeled INs from PV-Cre;Ai3-EYFP mice were immunopositive for parvalbumin but not somatostatin (D).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 1: Distribution of EYFP-labeled CA1 interneurons and specific colocalization with SOM and PV. A, B, Montage of fluorescence images showing the mostly nonoverlapping distribution of EYFP-labeled INs in the hippocampus from SOM-IRES-Cre;Ai3-EYFP (A) and PV-Cre;Ai3-EYFP (B) mice. Scale bars, 100 µm. In the CA1 region, EYFP-labeled INs of SOM-IRES-Cre;Ai3-EYFP mice are present mostly in the oriens and alveus regions, whereas EYFP-labeled INs of PV-Cre;Ai3-EYFP mice are found near or in the pyramidal cell layer. C, D, Representative examples of specific colocalization of EYFP-labeled INs (top, green) from SOM-IRES-Cre;Ai3-EYFP (C) and PV-Cre;Ai3-EYFP (D) mice with immunofluorescence for somatostatin (middle left, red) and parvalbumin (middle right, red), respectively. Merged images are shown at bottom. Scale bars, 10 µm. Nearly all CA1 EYFP-labeled INs from SOM-IRES-Cre;Ai3-EYFP mice colocalized with somatostatin but not parvalbumin (C). Conversely, mostly all CA1 EYFP-labeled INs from PV-Cre;Ai3-EYFP mice were immunopositive for parvalbumin but not somatostatin (D).
Mentions: SOM-INs or PV-INs were specifically labeled by breeding Ai3-EYFP reporter mice with SOM-IRES-Cre or PV-Cre mice, respectively. The distribution of EYFP-labelled SOM-INs and PV-INs interneurons was examined by fluorescence microscopy and their colocalization with somatostatin or parvalbumin was determined by immunofluorescence. Consistent with previous work (for review, see Freund and Buzsáki, 1996), the distribution of SOM-INs and PV-INs in the CA1 hippocampus was mostly nonoverlapping. EYFP-labeled SOM-IN somas were located mostly in stratum oriens and alveus of the CA1 and CA3 regions, as well as in the hilus of the dentate gyrus (Fig. 1A). EYFP-labeled PV-IN somas were mainly found in and around the pyramidal cell layer of CA1 and CA3 regions, and the granule cell layer of the dentate gyrus (Fig. 1B). We next verified the cell-specificity of the EYFP-labeling of CA1 interneurons by immunofluorescence. In SOM-IRES-Cre;Ai3-EYFP mice (Fig. 1C), 98.5% of EYFP-labeled interneurons in the CA1 region were immunopositive for somatostatin (n = 323 cells, 3 animals from 2 different litters), whereas only 6.9% of them were positive for parvalbumin (n = 354). In contrast in PV-Cre;Ai3-EYFP mice (Fig. 1D), 97.8% of EYFP-labeled CA1 interneurons were immunopositive for parvalbumin (n = 267 cells, 3 animals from 2 different litters), and only 10.7% were positive for somatostatin (n = 193 cells), thus confirming the specific labeling of mostly nonoverlapping CA1 populations of dendrite-projecting SOM-INs and perisomatic projecting PV-INs (Freund and Buzsáki, 1996; Tricoire et al., 2011) in the mice lines.

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.