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Differential expression of hyperpolarization-activated cyclic nucleotide-gated channel subunits during hippocampal development in the mouse.

Seo H, Seol MJ, Lee K - Mol Brain (2015)

Bottom Line: Each HCN channel isoform showed subfield-specific expression within the hippocampus from postnatal day 7, and only HCN4 was found in glial cells in the stratum lacunosum moleculare at this developmental stage.Furthermore, the immunolabeling for all these isoforms was colocalized with parvalbumin immunolabeling in interneurons of the CA field and in the dentate gyrus.Our mapping data showing the temporal and spatial changes in the expression of HCN channels suggest that HCN1, HCN2, and HCN4 subunits may have distinct physiological roles in the developing hippocampus.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Brain Science & Engineering Institute, Kyungpook National University Graduate School of Medicine, 2-101, Dongin-dong, Jung-gu, Daegu, 700-842, South Korea. hseo@knu.ac.kr.

ABSTRACT

Background: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels help control the rhythmic activation of pacemaker neurons during brain development. However, little is known about the timing and cell type specificity of the expression of HCN isoforms during development of the hippocampus.

Results: Here we examined the developmental expression of the brain-enriched HCN1, HCN2, and HCN4 isoforms of HCN channels in mouse hippocampus from embryonic to postnatal stages. All these isoforms were expressed abundantly in the hippocampus at embryonic day 14.5 and postnatal day 0. Each HCN channel isoform showed subfield-specific expression within the hippocampus from postnatal day 7, and only HCN4 was found in glial cells in the stratum lacunosum moleculare at this developmental stage. At postnatal days 21 and 56, all HCN isoforms were strongly expressed in the stratum lacunosum moleculare and the stratum pyramidale of the Cornu Ammonis (CA), as well as in the hilus of the dentate gyrus, but not in the subgranular zone. Furthermore, the immunolabeling for all these isoforms was colocalized with parvalbumin immunolabeling in interneurons of the CA field and in the dentate gyrus.

Conclusions: Our mapping data showing the temporal and spatial changes in the expression of HCN channels suggest that HCN1, HCN2, and HCN4 subunits may have distinct physiological roles in the developing hippocampus.

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Expression of HCN1 in parvalbumin (PV)-positive cells of the hippocampus at P21. (A, E, I): The strongest labeling for HCN1 was observed in the sl-m and alveus of the CA. Note also that its expression was gradually stronger in the so, sp, and sr of the CA2 (E) and CA3 (I) compared to CA1 (A). (A, B, D): PV-positive cells located in the sp of the CA1 did not show HCN1 immunolabeling, whereas PV-positive cells in the so or sr of the CA1 were labeled for HCN1. In the CA2, CA3, and hilus of the DG, most PV-immunopositive cells were labeled for HCN1. A-B, D: yellow arrows indicate PV-positive/HCN1-negative cells. A-B, D-F, H-J, L-N, P: white arrows indicate PV-positive/HCN1-positive cells. C, G, K, O: DAPI staining. Scale bars = 20 μm.
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Fig3: Expression of HCN1 in parvalbumin (PV)-positive cells of the hippocampus at P21. (A, E, I): The strongest labeling for HCN1 was observed in the sl-m and alveus of the CA. Note also that its expression was gradually stronger in the so, sp, and sr of the CA2 (E) and CA3 (I) compared to CA1 (A). (A, B, D): PV-positive cells located in the sp of the CA1 did not show HCN1 immunolabeling, whereas PV-positive cells in the so or sr of the CA1 were labeled for HCN1. In the CA2, CA3, and hilus of the DG, most PV-immunopositive cells were labeled for HCN1. A-B, D: yellow arrows indicate PV-positive/HCN1-negative cells. A-B, D-F, H-J, L-N, P: white arrows indicate PV-positive/HCN1-positive cells. C, G, K, O: DAPI staining. Scale bars = 20 μm.

Mentions: The strongest labeling for HCN1 was observed in the SL-M and alveus of the CA (Figure 3A, E, I); its expression was gradually stronger in the SO, SP, and SR of the CA2 (Figure 3E) and CA3 (Figure 3I) compared to the CA1 (Figure 3A). The most prominent immunolabeling for HCN2 and HCN4 subunits was observed in the SL-M and SP of the CA; this labeling was particularly strong in the CA3 compared to the CA1 or CA2 (Figures 4A, E, I and 5A, E, I). Interestingly, HCN2 and HCN4 subunits were not expressed in the alveus (Figures 4A, E, I and 5A, E, I), which, on the other hand, showed the most intense expression for HCN1 (Figure 3A, 3I). Moreover, we observed a relatively intense labeling for HCN1 in the SR of the CA, particularly in the CA3 (Figure 3e and i), compared to the expression of HCN2 (Figure 4E, I) and HCN4 (Figure 5E, I). In addition, immunoreactivity for HCN4 (Figure 5I), but not for HCN1 (Figure 3I) or HCN2 (Figure 4I), was present in the SL of the CA3.Figure 3


Differential expression of hyperpolarization-activated cyclic nucleotide-gated channel subunits during hippocampal development in the mouse.

Seo H, Seol MJ, Lee K - Mol Brain (2015)

Expression of HCN1 in parvalbumin (PV)-positive cells of the hippocampus at P21. (A, E, I): The strongest labeling for HCN1 was observed in the sl-m and alveus of the CA. Note also that its expression was gradually stronger in the so, sp, and sr of the CA2 (E) and CA3 (I) compared to CA1 (A). (A, B, D): PV-positive cells located in the sp of the CA1 did not show HCN1 immunolabeling, whereas PV-positive cells in the so or sr of the CA1 were labeled for HCN1. In the CA2, CA3, and hilus of the DG, most PV-immunopositive cells were labeled for HCN1. A-B, D: yellow arrows indicate PV-positive/HCN1-negative cells. A-B, D-F, H-J, L-N, P: white arrows indicate PV-positive/HCN1-positive cells. C, G, K, O: DAPI staining. Scale bars = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Fig3: Expression of HCN1 in parvalbumin (PV)-positive cells of the hippocampus at P21. (A, E, I): The strongest labeling for HCN1 was observed in the sl-m and alveus of the CA. Note also that its expression was gradually stronger in the so, sp, and sr of the CA2 (E) and CA3 (I) compared to CA1 (A). (A, B, D): PV-positive cells located in the sp of the CA1 did not show HCN1 immunolabeling, whereas PV-positive cells in the so or sr of the CA1 were labeled for HCN1. In the CA2, CA3, and hilus of the DG, most PV-immunopositive cells were labeled for HCN1. A-B, D: yellow arrows indicate PV-positive/HCN1-negative cells. A-B, D-F, H-J, L-N, P: white arrows indicate PV-positive/HCN1-positive cells. C, G, K, O: DAPI staining. Scale bars = 20 μm.
Mentions: The strongest labeling for HCN1 was observed in the SL-M and alveus of the CA (Figure 3A, E, I); its expression was gradually stronger in the SO, SP, and SR of the CA2 (Figure 3E) and CA3 (Figure 3I) compared to the CA1 (Figure 3A). The most prominent immunolabeling for HCN2 and HCN4 subunits was observed in the SL-M and SP of the CA; this labeling was particularly strong in the CA3 compared to the CA1 or CA2 (Figures 4A, E, I and 5A, E, I). Interestingly, HCN2 and HCN4 subunits were not expressed in the alveus (Figures 4A, E, I and 5A, E, I), which, on the other hand, showed the most intense expression for HCN1 (Figure 3A, 3I). Moreover, we observed a relatively intense labeling for HCN1 in the SR of the CA, particularly in the CA3 (Figure 3e and i), compared to the expression of HCN2 (Figure 4E, I) and HCN4 (Figure 5E, I). In addition, immunoreactivity for HCN4 (Figure 5I), but not for HCN1 (Figure 3I) or HCN2 (Figure 4I), was present in the SL of the CA3.Figure 3

Bottom Line: Each HCN channel isoform showed subfield-specific expression within the hippocampus from postnatal day 7, and only HCN4 was found in glial cells in the stratum lacunosum moleculare at this developmental stage.Furthermore, the immunolabeling for all these isoforms was colocalized with parvalbumin immunolabeling in interneurons of the CA field and in the dentate gyrus.Our mapping data showing the temporal and spatial changes in the expression of HCN channels suggest that HCN1, HCN2, and HCN4 subunits may have distinct physiological roles in the developing hippocampus.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Brain Science & Engineering Institute, Kyungpook National University Graduate School of Medicine, 2-101, Dongin-dong, Jung-gu, Daegu, 700-842, South Korea. hseo@knu.ac.kr.

ABSTRACT

Background: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels help control the rhythmic activation of pacemaker neurons during brain development. However, little is known about the timing and cell type specificity of the expression of HCN isoforms during development of the hippocampus.

Results: Here we examined the developmental expression of the brain-enriched HCN1, HCN2, and HCN4 isoforms of HCN channels in mouse hippocampus from embryonic to postnatal stages. All these isoforms were expressed abundantly in the hippocampus at embryonic day 14.5 and postnatal day 0. Each HCN channel isoform showed subfield-specific expression within the hippocampus from postnatal day 7, and only HCN4 was found in glial cells in the stratum lacunosum moleculare at this developmental stage. At postnatal days 21 and 56, all HCN isoforms were strongly expressed in the stratum lacunosum moleculare and the stratum pyramidale of the Cornu Ammonis (CA), as well as in the hilus of the dentate gyrus, but not in the subgranular zone. Furthermore, the immunolabeling for all these isoforms was colocalized with parvalbumin immunolabeling in interneurons of the CA field and in the dentate gyrus.

Conclusions: Our mapping data showing the temporal and spatial changes in the expression of HCN channels suggest that HCN1, HCN2, and HCN4 subunits may have distinct physiological roles in the developing hippocampus.

Show MeSH