Roles of GSK3β in Odor Habituation and Spontaneous Neural Activity of the Mouse Olfactory Bulb

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.

“Till Death Do Us Part”: A Potential Irreversible Link Between Aberrant Cell Cycle Control and Neurodegeneration in the Adult Olfactory Bulb

“…The implication of CCE in the formation of neurotoxic protein inclusions is yet to be established in the adult OB, but there is compelling evidence that this is likely possible. The tau kinase GSK3β (upregulated in models of AD) is abundantly expressed in the adult OB where it is essential in mediating spontaneous neural activity and odor habituation (Xu et al, 2013 ). Likewise, the focal adhesion kinase (FAK), thought to regulate cyclin D1 and being also involved in AD pathology (Caltagarone et al, 2007 ), is deregulated early in the OB of APP/PS1 mouse model prior to β-amyloid plaque formation (Lachen-Montes et al, 2016 ).…”

Notch1 activity in the olfactory bulb is odour‐dependent and contributes to olfactory behaviour

“…The neural signal is then conveyed to underlying mitral cells (MCs), which relay the signal to the piriform cortex, the entorhinal cortex and the amygdala (Mori & Yoshihara, ). The physiological properties of the olfactory circuit have been well characterised; nevertheless, few reports have addressed signalling mechanisms regulating neuronal communication and olfactory behaviour (Cao et al ., ; Hellwig et al ., ; Néant‐Fery et al ., ; Xu et al ., ). Interestingly, olfaction is the first sense which is affected in Alzheimer's disease (Rahayel et al ., ) and it has been proposed that alteration in synaptic transmission may underlie the olfactory deficit.…”

Lithium-associated transcriptional regulation of CRMP1 in patient-derived olfactory neurons and symptom changes in bipolar disorder

“…Glycogen synthase kinase 3β (GSK3β), a well-documented candidate gene of BD is abundantly expressed in the olfactory bulb (OB), where it regulates the axonal stability in olfactory neurons 18 , 19 . While evidence for relevance of GSK3β in BD has historically focused on its activity levels, recent studies in human brain autopsies suggest that its mRNA levels are also altered in the prefrontal cortex of patients with BD, compared to non-bipolar controls 20 .…”