Age-Related Unstructured Spike Patterns Patterns and Molecular Localization in Drosophila Circadian Neurons
Aging decreases sleep quality by disrupting the molecular machinery that regulates the circadian rhythm. However, we do not fully understand the mechanism that underlies this process. In Drosophila, sleep quality is regulated by precisely timed patterns of spontaneous firing activity in posterior DN1 (DN1p) circadian clock neurons. How aging affects the physiological function of DN1p neurons is unknown. In this study, we found that aging altered functional parameters related to neural excitability and disrupted patterned spike sequences in DN1p neurons during nighttime. We also characterized age-associated changes in intrinsic membrane properties related to spike frequency adaptations and synaptic properties, which may account for the unstructured spike patterns in aged DN1p neurons. Because Slowpoke binding protein (SLOB) and the Na+/K+ ATPase β subunit (NaKβ) regulate clock-dependent spiking patterns in circadian networks, we compared the subcellular organization of these factors between young and aged DN1p neurons. Young DN1p neurons showed circadian cycling of HA-tagged SLOB and myc-tagged NaKβ targeting the plasma membrane, whereas aged DN1p neurons showed significantly disrupted subcellular localization patterns of both factors. The distribution of SLOB and NaKβ signals also showed greater variability in young vs. aged DN1p neurons, suggesting aging leads to a loss of actively formed heterogeneity for these factors. These findings showed that aging disrupts precisely structured molecular patterns that regulate structured neural activity in the circadian network, leading to age-associated declines in sleep quality. Thus, it is possible to speculate that a recovery of unstructured neural activity in aging clock neurons could help to rescue age-related poor sleep quality.
Nguyen, D. L., Hutson, A. N., Zhang, Y., Daniels, S. D., Peard, A. R., & Tabuchi, M. (2022)
In Frontiers in Physiology (Vol. 13).
Neddylation is critical to cortical development by regulating Wnt/b-catenin signaling.
The neocortex is characterized by a six-layered structure that is critical to brain function. Cortical development requires proper generation and differentiation of neurons that migrate out from the ventricular zone to populate the cortex. This is regulated by Wnt/β-catenin signaling, which reduces gradually during cortical development. However, how the decreasing of Wnt/β-catenin signaling is regulated is largely unclear. We demonstrate that neddylation, a ubiquitylation-like protein posttranslational modification, targets β-catenin itself to inhibit Wnt/β-catenin signaling in the process. We also show that ablating Nae1, an obligative subunit of the E1 for neddylation, from cortical progenitor cells leads to similar phenotypes in β-catenin gain-of-function mice. This study reveals a previously unappreciated role of neddylation in regulating cortical lamination by targeting β-catenin signaling.
L. Zhang, H. Jing, H. Li, W. Chen, B. Luo, H-S. Zhang, Z-Q. Dong, L. Li, H-B. Su, W-C. Xiong and L. Mei.
Proc. Nat. Acad. Sci. USA. 117:26448-26459, 2020 Oct
Topographic heterogeneity of intrinsic excitability in mouse hippocampal CA3 pyramidal neurons.
Area CA3 is a major hippocampal region that is classically thought to act as a homogeneous neural network vital for spatial navigation and episodic memories. Here, we report that CA3 pyramidal neurons exhibit marked heterogeneity of somatodendritic morphology and cellular electrical properties along both proximodistal and dorsoventral axes. These new results uncover a complex, yet orderly, pattern of topographic organization of CA3 neuronal features that may contribute to its in vivo functional diversity.
Sun Q, Jiang YQ, Lu MC.
J Neurophysiol. 2020 Oct 1;124(4):1270-1284. doi: 10.1152/jn.00147.2020. Epub 2020 Sep 16.
A role of lamin A/C in preventing neuromuscular junction decline in mice.
This study provides evidence that lamin A/C, a scaffolding component of the nuclear envelope, is critical to maintaining the NMJ in mice. Its muscle-specific mutation led to progressive NMJ degeneration in vivo. We showed that the mutation reduced the level of rapsyn, a protein necessary for acetylcholine receptor (AChR) clustering; and expression of rapsyn in muscles attenuated NMJ deficits of HSA-Lmna−/− mice. These results reveal a role of lamin A/C in NMJ maintenance and suggest that nuclear dysfunction or deficiency may contribute to NMJ deficits in aged muscles.
N. Gao, K. Zhao, Y. Cao, X. Ren, H. Jing, G. Xing, W.-C. Xiong, and Lin Mei.
J. Neurosci. 40:7203-7215, 2020 Sept (Cover)
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A role of low-density lipoprotein receptor-related protein 4 (LRP4) in astrocytic Aβ clearance.
This study investigates how astrocytes, a type of non-nerve cells in the brain, may contribute to Alzheimer's disease (AD) development. We demonstrate that the low-density lipoprotein receptor-related protein 4 (LRP4) is reduced in the brain of AD patients. Mimicking the reduced levels in an AD mouse model exacerbates cognitive impairment and increases amyloid aggregates that are known to damage the brain. We show that LRP4 could promote the clearance of amyloid protein by astrocytes. Our results reveal a previously unappreciated role of LRP4 in AD development.
H. Zhang, W. Chen, Z. Tan, L. Zhang, Z. Dong, W. Cui, K. Zhao, H. Wang, H. Jing, R. Cao, C. Kim, J.G. Safar, W.-C. Xiong and L. Mei.
J. Neurosci., 40:5347:5361, 2020 Jul
Clinical features of LRP4/agrin-antibody – positive myasthenia gravis: A multicenter study.
M.H. Rivner, B.M. Quarles, J.-X. Pan, Z. Yu, J.F. Howard Jr, A. Corse, M.M. Dimachkie, C. Jackson, T. Vu, G. Small, R.P. Lisak, J. Belsh, I. Lee, R.J. Nowak, V. Baute, S. Scelsa, J.A. Fernandes, Z. Simmons, A. Swenson, R. Barohn, R.B. Sanka, C. Gooch, E. Ubogu, J. Caress, M. Pasnoor, H. Xu, L. Mei.
Muscle & Nerve 62:333–343, 2020 Jun.
Detection of Neutrophils in the Sciatic Nerve Following Peripheral Nerve Injury.
Niemi JP, Lindborg JA, Zigmond RE.
Methods Mol Biol. 2020 Jun;2143:207-222. doi: 10.1007/978-1-0716-0585-1_16.
Rapsyn as a signaling and scaffolding molecule in NMJ formation and maintenance.
G. Xing, W.C. Xiong, L. Mei.
Neurosci. Lett. 731:1350132, 2020 Apr (invited review)
Regulation of autophagy by inhibitory CSPG interactions with receptor PTPσ and its impact on plasticity and regeneration after spinal cord injury.
Tran AP, Warren PM, Silver J.
Exp Neurol. 2020 Jun;328:113276. doi: 10.1016/j.expneurol.2020.113276. Epub 2020 Mar 4. PMID: 32145250 Review.
CUL3 Deficiency Causes Social Deficits and Anxiety-like Behaviors by Impairing Excitation-Inhibition Balance through the Promotion of Cap-Dependent Translation.
Z. Dong*, W. Chen*, C. Chen, H. Wang, W. Cui, Z. Tan, H. Robinson, N. Gao, B. Luo, L. Zhang, K. Zhao, W.C. Xiong and L. Mei.
Neuron 105: 475-490, 2020 Feb (Cover; Preview by Chen & Maher, Neuron, 105:398-399, 2020).
Read more about the cover here.
Cathepsins in neuronal plasticity.
Tran AP, Silver J.
Neural Regen Res. 2021 Jan;16(1):26-35. doi: 10.4103/1673-5374.286948. PMID: 32788444
Phrenic-specific transcriptional programs shape respiratory motor output
eLife 2020;9:e52859, Jan 16, 2020
Coupling of terminal differentiation deficit with neurodegenerative pathology in Vps35-deficient pyramidal neurons
Cell Death & Differentiation, Published: 06 January 2020
Functional Specialization of Interneuron Dendrites: Identification of Action Potential Initiation Zone in Axonless Olfactory Bulb Granule Cells
The Journal of Neurosciences, 4 December 2019, 39 (49) 9674-9688
The calcium channel subunit α2δ-3 organizes synapses via an activity-dependent and autocrine BMP signaling pathway
Nature Communications,10, 5575 (2019)
Cullin 3, a risk gene of autism and schizophrenia, in protein translation for E-I balance and regulation of social and anxiety-like behaviors.
A cover and preview for this paper can be found here
A mechanism in Agrin signaling revealed by a prevalent Rapsyn mutation in congenital myasthenic syndrome
Lmx1b is required at multiple stages to build expansive serotonergic axon architectures
eLife 2019;8:e48788
Neogenin-loss in neural crest cells results in persistent hyperplastic primary vitreous formation
Journal of Molecular Cell Biology, 23 July 2019
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Agrin-Lrp4-Ror2 signaling regulates adult hippocampal neurogenesis in mice
Elife. 2019 Jul 3;8.
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pHluorin-BACE1-mCherry Acts as a Reporter for the Intracellular Distribution of Active BACE1 In Vitro and In Vivo
Cells. 2019 May 17;8(5)
Selective attenuation of Ether-a-go-go related K+ currents by endogenous acetylcholine reduces spike-frequency adaptation and network correlation
Elife. 2019 Apr 29;8.
Archive
Dying Neurons Utilize Innate Immune Signaling to Prime Glia for Phagocytosis during Development
Developmental Cell | 48(4):506-22. Featured article; Cover article
Lack of myosin X enhances osteoclastogenesis and increases cell surface Unc5b in osteoclast-lineage cells
Journal of Bone and Mineral Research (JBMR) | 15 January 2019, 34(5):939-954 |
Macrophage biology in the peripheral nervous system after injury
Progress in Neurobiology | 173, Pages 102-121, 2019