BMPR-2 gates activity-dependent stabilization of primary dendrites during mitral cell remodeling

Aihara, Shuhei; Fujimoto, Satoshi; Sakaguchi, Richi; Imai, Takeshi

doi:10.1016/j.celrep.2021.109276

Cited by 20 publications

(22 citation statements)

References 64 publications

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“…Previous studies indicated that various types of Rho GTPases regulate activity-dependent dendrite morphogenesis, including growth and retraction (Li et al, 2002; Luo, 2000; Murakoshi et al, 2011; Sin et al, 2002). Using CRISPR-Cas9-based screening in mitral cells (Aihara et al, 2021), we found that Rho subfamily GTPases are required for dendrite pruning (Figure 4H). When all of the Rho subfamily GTPases (RhoA, RhoB, and RhoC) were knocked out in mitral cells (RhoABC TKO), dendrite pruning was prevented.…”

Section: Resultsmentioning

confidence: 99%

“…The subsequent depolarization induces the neuron-wide activation of RhoA, leading to the pruning of non-protected dendrites (lateral inhibition). NMDAR-dependent local signals also activate Rac1 to stabilize the dendrite (Aihara et al ., 2021). Scale bars, 20 μm in (A) and (C) left; 5 μm in (C) right.…”

Section: Resultsmentioning

confidence: 99%

“…Once one dendrite forms strong glutamatergic synapses, it will be further strengthened by Hebbian LTP via Rac1 (positive-feedback) (Aihara et al ., 2021), while others will be further eliminated by lateral inhibition with RhoA (Figure 6H and 6I). Rac1 and RhoA seem to mediate actin fiber assembly and disassembly to facilitate neurite extension and retraction, respectively (Aihara et al ., 2021; Luo, 2000). Notably, NMDARs are involved in synaptic competition in various systems (Personius et al, 2016; Rabacchi et al, 1992; Wong and Ghosh, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Mutant DORA-RhoA has a mutation in PKN1 (L59Q) preventing RhoA binding (van Unen et al ., 2015). pCAGGS-RaichuEV-Rac1 was described previously (Aihara et al ., 2021; Komatsu et al, 2011). Plasmids were introduced at E12 by in utero electroporation.…”

Section: Methods Detailsmentioning

confidence: 99%

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Activity-dependent lateral inhibition signals for synaptic competition

Fujimoto¹,

Leiwe²,

Sakaguchi

et al. 2019

Preprint

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In the mouse olfactory bulb, sensory information detected by ~1,000 types of olfactory sensory neurons (OSNs) is represented by the glomerular map. The second-order neurons, mitral and tufted cells, connect a single primary dendrite to one glomerulus. This forms discrete connectivity between the ~1,000 types of input and output neurons. It has remained unknown how this discrete dendrite wiring is established during development. We found that genetically silencing neuronal activity in mitral cells, but not from OSNs, perturbs the dendrite pruning of mitral cells. In vivo calcium imaging of awake neonatal animals revealed two types of spontaneous neuronal activity in mitral/tufted cells, but not in OSNs. Pharmacological and knockout experiments revealed a role for glutamate and NMDARs. The genetic blockade of neurotransmission among mitral/tufted cells reduced spontaneous activity and perturbed dendrite wiring. Thus, spontaneous network activity generated within the olfactory bulb self-organizes the parallel discrete connections in the mouse olfactory system.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methods Detailsmentioning

confidence: 99%

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Activity-dependent lateral inhibition signals for synaptic competition

Fujimoto¹,

Leiwe²,

Sakaguchi

et al. 2019

Preprint

Self Cite

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“…Evidence for signalling pathways that distinguish 'to-be-pruned' versus 'to-be-stabilised' dendrites remains a key target for the near future. However, permissive regulators of this process have been recently identified (Aihara et al, 2021), and there is a strong link between OSN-driven dendrite stabilisation and activity-dependent strengthening of OSN-to-M/TC synaptic connections (Inoue et al, 2018(Inoue et al, , 2021.…”

Section: Astrocytesmentioning

confidence: 99%

Development of the mammalian main olfactory bulb

et al. 2022

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The mammalian main olfactory bulb is a crucial processing centre for the sense of smell. The olfactory bulb forms early during development and is functional from birth. However, the olfactory system continues to mature and change throughout life as a target of constitutive adult neurogenesis. Our Review synthesises current knowledge of prenatal, postnatal and adult olfactory bulb development, focusing on the maturation, morphology, functions and interactions of its diverse constituent glutamatergic and GABAergic cell types. We highlight not only the great advances in the understanding of olfactory bulb development made in recent years, but also the gaps in our present knowledge that most urgently require addressing.

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Ketamine’s rapid and sustained antidepressant effects are driven by distinct mechanisms

Rawat,

Tunc-Ozcan,

Dunlop

et al. 2024

Cell. Mol. Life Sci.

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Administration of multiple subanesthetic doses of ketamine increases the duration of antidepressant effects relative to a single ketamine dose, but the mechanisms mediating this sustained effect are unclear. Here, we demonstrate that ketamine’s rapid and sustained effects on affective behavior are mediated by separate and temporally distinct mechanisms. The rapid effects of a single dose of ketamine result from increased activity of immature neurons in the hippocampal dentate gyrus without an increase in neurogenesis. Treatment with six doses of ketamine over two weeks doubled the duration of behavioral effects after the final ketamine injection. However, unlike ketamine’s rapid effects, this more sustained behavioral effect did not correlate with increased immature neuron activity but instead correlated with increased numbers of calretinin-positive and doublecortin-positive immature neurons. This increase in neurogenesis was associated with a decrease in bone morphogenetic protein (BMP) signaling, a known inhibitor of neurogenesis. Injection of a BMP4-expressing lentivirus into the dentate gyrus maintained BMP signaling in the niche and blocked the sustained – but not the rapid – behavioral effects of ketamine, indicating that decreased BMP signaling is necessary for ketamine’s sustained effects. Thus, although the rapid effects of ketamine result from increased activity of immature neurons in the dentate gyrus without requiring an increase in neurogenesis, ketamine’s sustained effects require a decrease in BMP signaling and increased neurogenesis along with increased neuron activity. Understanding ketamine’s dual mechanisms of action should help with the development of new rapid-acting therapies that also have safe, reliable, and sustained effects.

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BMPR-2 gates activity-dependent stabilization of primary dendrites during mitral cell remodeling

Cited by 20 publications

References 64 publications

Activity-dependent lateral inhibition signals for synaptic competition

Activity-dependent lateral inhibition signals for synaptic competition

Development of the mammalian main olfactory bulb

Ketamine’s rapid and sustained antidepressant effects are driven by distinct mechanisms

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