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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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Selective inhibition of GSK3β activity in the OB impairs odor cross-habituation.A: The investigation time of trial one in each block (each odor) did not show a statistically significant difference between the TDZD-8 and vehicle-treated group (P>0.05). B: The latencies of each block in the TDZD-8- and vehicle-treated animals were not significantly different (P>0.05). C: The investigation time of each block and each trial. The TDZD-8 treated group displayed habituation only to vanillin, while the vehicle-treated group habituated to all six of the tested odors. D & E: Compared to the vehicle-treated animals, the habituation index (P<0.05) and odor cross-habituation index (P<0.05) in the TDZD-8-treated animals decreased significantly. The data were obtained from 16 animals in the vehicle group and 12 animals in the TDZD-8 group. * P<0.05, ** P<0.01. The group data shown are the average ± SEM.
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pone-0063598-g006: Selective inhibition of GSK3β activity in the OB impairs odor cross-habituation.A: The investigation time of trial one in each block (each odor) did not show a statistically significant difference between the TDZD-8 and vehicle-treated group (P>0.05). B: The latencies of each block in the TDZD-8- and vehicle-treated animals were not significantly different (P>0.05). C: The investigation time of each block and each trial. The TDZD-8 treated group displayed habituation only to vanillin, while the vehicle-treated group habituated to all six of the tested odors. D & E: Compared to the vehicle-treated animals, the habituation index (P<0.05) and odor cross-habituation index (P<0.05) in the TDZD-8-treated animals decreased significantly. The data were obtained from 16 animals in the vehicle group and 12 animals in the TDZD-8 group. * P<0.05, ** P<0.01. The group data shown are the average ± SEM.

Mentions: Since GSK3β activity was dependent on neural activity and its inhibition reduced the spontaneous neural activity, the kinase activity might play roles in olfactory information processing. Thus, we tested the potential functions of GSK3β in olfaction using behavioral analysis. Mice were bilaterally implanted with stainless cannulas into the OBs and allowed to recover for 3 weeks. After that we locally inhibited the activity of GSK3β with TDZD-8 and assessed the olfactory performance by odor cross-habituation test (Fig. 5). The investigation time (Fig. 6A, P>0.05) and latency (Fig. 6B, P>0.05) of trial one in each block for each odor did not show statistically significant differences between the vehicle- and TDZD-8-treated groups, suggesting that these mice can detect and discriminate odors normally. However, when analyzing the habituation process in each block, we found that the TDZD-8-treated mice habituated normally to only one odor, while the vehicle-treated mice habituated to all six of the tested odors (Fig. 6C). Moreover, the habituation index (Fig. 6D, P<0.05) and cross-habituation index (Fig. 6E, P<0.05) were significantly different between the vehicle- and the TDZD-8-treated groups. These findings demonstrated that mice could detect and discriminate odors after the inhibition of GSK3β; however, their discrimination and habituation abilities were significantly impaired. Thus, our findings suggest that GSK3β is required for normal olfactory functions.


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)

Selective inhibition of GSK3β activity in the OB impairs odor cross-habituation.A: The investigation time of trial one in each block (each odor) did not show a statistically significant difference between the TDZD-8 and vehicle-treated group (P>0.05). B: The latencies of each block in the TDZD-8- and vehicle-treated animals were not significantly different (P>0.05). C: The investigation time of each block and each trial. The TDZD-8 treated group displayed habituation only to vanillin, while the vehicle-treated group habituated to all six of the tested odors. D & E: Compared to the vehicle-treated animals, the habituation index (P<0.05) and odor cross-habituation index (P<0.05) in the TDZD-8-treated animals decreased significantly. The data were obtained from 16 animals in the vehicle group and 12 animals in the TDZD-8 group. * P<0.05, ** P<0.01. The group data shown are the average ± SEM.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3643914&req=5

pone-0063598-g006: Selective inhibition of GSK3β activity in the OB impairs odor cross-habituation.A: The investigation time of trial one in each block (each odor) did not show a statistically significant difference between the TDZD-8 and vehicle-treated group (P>0.05). B: The latencies of each block in the TDZD-8- and vehicle-treated animals were not significantly different (P>0.05). C: The investigation time of each block and each trial. The TDZD-8 treated group displayed habituation only to vanillin, while the vehicle-treated group habituated to all six of the tested odors. D & E: Compared to the vehicle-treated animals, the habituation index (P<0.05) and odor cross-habituation index (P<0.05) in the TDZD-8-treated animals decreased significantly. The data were obtained from 16 animals in the vehicle group and 12 animals in the TDZD-8 group. * P<0.05, ** P<0.01. The group data shown are the average ± SEM.
Mentions: Since GSK3β activity was dependent on neural activity and its inhibition reduced the spontaneous neural activity, the kinase activity might play roles in olfactory information processing. Thus, we tested the potential functions of GSK3β in olfaction using behavioral analysis. Mice were bilaterally implanted with stainless cannulas into the OBs and allowed to recover for 3 weeks. After that we locally inhibited the activity of GSK3β with TDZD-8 and assessed the olfactory performance by odor cross-habituation test (Fig. 5). The investigation time (Fig. 6A, P>0.05) and latency (Fig. 6B, P>0.05) of trial one in each block for each odor did not show statistically significant differences between the vehicle- and TDZD-8-treated groups, suggesting that these mice can detect and discriminate odors normally. However, when analyzing the habituation process in each block, we found that the TDZD-8-treated mice habituated normally to only one odor, while the vehicle-treated mice habituated to all six of the tested odors (Fig. 6C). Moreover, the habituation index (Fig. 6D, P<0.05) and cross-habituation index (Fig. 6E, P<0.05) were significantly different between the vehicle- and the TDZD-8-treated groups. These findings demonstrated that mice could detect and discriminate odors after the inhibition of GSK3β; however, their discrimination and habituation abilities were significantly impaired. Thus, our findings suggest that GSK3β is required for normal olfactory functions.

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