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Roles of GSK3β in odor habituation and spontaneous neural activity of the mouse olfactory bulb.

Xu Z, Wang L, Chen G, Rao X, Xu F - PLoS ONE (2013)

Bottom Line: Here, we studied the possible functions of GSK3β activity in the OB.When GSK3β activity was reduced by a selective inhibitor, the spontaneous oscillatory activity was significantly decreased in the granule cell layer of the OB.Furthermore, local inhibition of GSK3β activity in the OB significantly impaired the odor habituation ability.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, the Chinese Academy of Sciences, Wuhan, China.

ABSTRACT
Glycogen synthase kinase 3β (GSK3β), a multifaceted kinase, is abundantly expressed in the brain, including the olfactory bulb (OB). In resting cells, GSK3β is constitutively active, and its over-activation is presumably involved in numerous brain diseases, such as Alzheimer's disease. However, the functions of the constitutively active GSK3β in the adult brain under physiological conditions are not well understood. Here, we studied the possible functions of GSK3β activity in the OB. Odor stimulation, or blockade of peripheral olfactory inputs caused by either transgenic knock-out or ZnSO4 irrigation to the olfactory epithelium, all affected the expression level of GSK3β in the OB. When GSK3β activity was reduced by a selective inhibitor, the spontaneous oscillatory activity was significantly decreased in the granule cell layer of the OB. Furthermore, local inhibition of GSK3β activity in the OB significantly impaired the odor habituation ability. These results suggest that GSK3β plays important roles in both spontaneous neural activity and odor information processing in the OB, deepening our understanding of the potential functions of the constitutively active GSK3β in the brain under physiological conditions.

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Olfactory deficit reduced the expression level of GSK3β in the OB.A: T-GSK3β was widely expressed in the mouse OB, including the mitral cells and granule cells. B: The T-GSK3β signal was significantly decreased in the OBs of CNGX mice. C: The T-GSK3β signal was decreased one month after ZnSO4 irrigation. D: The T-GSK3β expression level in OB was partially recovered four months after ZnSO4 irrigation. (A–D: white arrow, mitral cell layer; yellow arrow, granular cell layer). E & F: Compared to the signal at one month following ZnSO4 irrigation, Syn in the OB was stronger at four months post-treatment (E–F: white arrow, glomerulus). Syn: synaptophysin; Scale bar, A–D, 100 µm; E–F, 50 µm.
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pone-0063598-g001: Olfactory deficit reduced the expression level of GSK3β in the OB.A: T-GSK3β was widely expressed in the mouse OB, including the mitral cells and granule cells. B: The T-GSK3β signal was significantly decreased in the OBs of CNGX mice. C: The T-GSK3β signal was decreased one month after ZnSO4 irrigation. D: The T-GSK3β expression level in OB was partially recovered four months after ZnSO4 irrigation. (A–D: white arrow, mitral cell layer; yellow arrow, granular cell layer). E & F: Compared to the signal at one month following ZnSO4 irrigation, Syn in the OB was stronger at four months post-treatment (E–F: white arrow, glomerulus). Syn: synaptophysin; Scale bar, A–D, 100 µm; E–F, 50 µm.

Mentions: If constitutively active GSK3β plays important roles in the neural activity, its expression in OB should be affected accordingly by the conditions of olfactory sensory inputs. To test this assumption, transgenic mice (Cyclic nucleotide gated channel 2 knockout, CNGX) were used [20], [21]. The ion channel is necessary for OSNs to generate odor induced action potentials, rendering CNGX mice essentially anosmic. Using immunohistochemistry (IHC), we found that the signal of total-GSK3β (T-GSK3β) in the OB of CNGX mice was remarkably decreased in the mitral cell and granule cell layers (Fig. 1A–B). To provide quantitative information and confirm the IHC results, Western blotting analysis was performed. Compared with the WT OBs, there was indeed a significant reduction of T-GSK3β signal in the CNGX OBs (Fig. 2A; n = 6 in each group, P<0.05).


Roles of GSK3β in odor habituation and spontaneous neural activity of the mouse olfactory bulb.

Xu Z, Wang L, Chen G, Rao X, Xu F - PLoS ONE (2013)

Olfactory deficit reduced the expression level of GSK3β in the OB.A: T-GSK3β was widely expressed in the mouse OB, including the mitral cells and granule cells. B: The T-GSK3β signal was significantly decreased in the OBs of CNGX mice. C: The T-GSK3β signal was decreased one month after ZnSO4 irrigation. D: The T-GSK3β expression level in OB was partially recovered four months after ZnSO4 irrigation. (A–D: white arrow, mitral cell layer; yellow arrow, granular cell layer). E & F: Compared to the signal at one month following ZnSO4 irrigation, Syn in the OB was stronger at four months post-treatment (E–F: white arrow, glomerulus). Syn: synaptophysin; Scale bar, A–D, 100 µm; E–F, 50 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643914&req=5

pone-0063598-g001: Olfactory deficit reduced the expression level of GSK3β in the OB.A: T-GSK3β was widely expressed in the mouse OB, including the mitral cells and granule cells. B: The T-GSK3β signal was significantly decreased in the OBs of CNGX mice. C: The T-GSK3β signal was decreased one month after ZnSO4 irrigation. D: The T-GSK3β expression level in OB was partially recovered four months after ZnSO4 irrigation. (A–D: white arrow, mitral cell layer; yellow arrow, granular cell layer). E & F: Compared to the signal at one month following ZnSO4 irrigation, Syn in the OB was stronger at four months post-treatment (E–F: white arrow, glomerulus). Syn: synaptophysin; Scale bar, A–D, 100 µm; E–F, 50 µm.
Mentions: If constitutively active GSK3β plays important roles in the neural activity, its expression in OB should be affected accordingly by the conditions of olfactory sensory inputs. To test this assumption, transgenic mice (Cyclic nucleotide gated channel 2 knockout, CNGX) were used [20], [21]. The ion channel is necessary for OSNs to generate odor induced action potentials, rendering CNGX mice essentially anosmic. Using immunohistochemistry (IHC), we found that the signal of total-GSK3β (T-GSK3β) in the OB of CNGX mice was remarkably decreased in the mitral cell and granule cell layers (Fig. 1A–B). To provide quantitative information and confirm the IHC results, Western blotting analysis was performed. Compared with the WT OBs, there was indeed a significant reduction of T-GSK3β signal in the CNGX OBs (Fig. 2A; n = 6 in each group, P<0.05).

Bottom Line: Here, we studied the possible functions of GSK3β activity in the OB.When GSK3β activity was reduced by a selective inhibitor, the spontaneous oscillatory activity was significantly decreased in the granule cell layer of the OB.Furthermore, local inhibition of GSK3β activity in the OB significantly impaired the odor habituation ability.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, the Chinese Academy of Sciences, Wuhan, China.

ABSTRACT
Glycogen synthase kinase 3β (GSK3β), a multifaceted kinase, is abundantly expressed in the brain, including the olfactory bulb (OB). In resting cells, GSK3β is constitutively active, and its over-activation is presumably involved in numerous brain diseases, such as Alzheimer's disease. However, the functions of the constitutively active GSK3β in the adult brain under physiological conditions are not well understood. Here, we studied the possible functions of GSK3β activity in the OB. Odor stimulation, or blockade of peripheral olfactory inputs caused by either transgenic knock-out or ZnSO4 irrigation to the olfactory epithelium, all affected the expression level of GSK3β in the OB. When GSK3β activity was reduced by a selective inhibitor, the spontaneous oscillatory activity was significantly decreased in the granule cell layer of the OB. Furthermore, local inhibition of GSK3β activity in the OB significantly impaired the odor habituation ability. These results suggest that GSK3β plays important roles in both spontaneous neural activity and odor information processing in the OB, deepening our understanding of the potential functions of the constitutively active GSK3β in the brain under physiological conditions.

Show MeSH
Related in: MedlinePlus