LTP of inhibition at PV interneuron output synapses requires developmental BMP signaling

Vickers, Evan; Osypenko, Denys; Clark, Christopher; Okur, Zeynep; Scheiffele, Peter; Schneggenburger, Ralf

doi:10.1038/s41598-020-66862-5

Cited by 9 publications

(6 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2C). Of note, recent genetic experiments have illustrated that Bmpr1a guides specific synaptic connectivity in PVALB interneurons [80,81]. In addition, we found few other genes with opposite trend of differential expression between sister lineages, also associated with synaptic pruning and maturation of interneurons.…”

Section: Rhepo Modulates Gene Expression Of Interneuronal Subpopulati...supporting

confidence: 50%

Erythropoietin restrains the inhibitory potential of interneurons in the mouse hippocampus

Curto,

Carceller,

Klimczak

et al. 2024

Mol Psychiatry

View full text Add to dashboard Cite

Severe psychiatric illnesses, for instance schizophrenia, and affective diseases or autism spectrum disorders, have been associated with cognitive impairment and perturbed excitatory-inhibitory balance in the brain. Effects in juvenile mice can elucidate how erythropoietin (EPO) might aid in rectifying hippocampal transcriptional networks and synaptic structures of pyramidal lineages, conceivably explaining mitigation of neuropsychiatric diseases. An imminent conundrum is how EPO restores synapses by involving interneurons. By analyzing ~12,000 single-nuclei transcriptomic data, we generated a comprehensive molecular atlas of hippocampal interneurons, resolved into 15 interneuron subtypes. Next, we studied molecular alterations upon recombinant human (rh)EPO and saw that gene expression changes relate to synaptic structure, trans-synaptic signaling and intracellular catabolic pathways. Putative ligand-receptor interactions between pyramidal and inhibitory neurons, regulating synaptogenesis, are altered upon rhEPO. An array of in/ex vivo experiments confirms that specific interneuronal populations exhibit reduced dendritic complexity, synaptic connectivity, and changes in plasticity-related molecules. Metabolism and inhibitory potential of interneuron subgroups are compromised, leading to greater excitability of pyramidal neurons. To conclude, improvement by rhEPO of neuropsychiatric phenotypes may partly owe to restrictive control over interneurons, facilitating re-connectivity and synapse development.

show abstract

Section: Rhepo Modulates Gene Expression Of Interneuronal Subpopulati...supporting

confidence: 50%

Erythropoietin restrains the inhibitory potential of interneurons in the mouse hippocampus

Curto,

Carceller,

Klimczak

et al. 2024

Mol Psychiatry

View full text Add to dashboard Cite

show abstract

“…Multiple FMRP-dependent secreted signals likely mediate intercellular communication between neurons and glia in brain development and circuit remodeling ( Figure 2 ). In the CNS, BMPs modulate neuronal metabolism ( Xu et al, 2017 ; Jensen et al, 2021 ), synaptic plasticity ( Vickers et al, 2020 ; Jensen et al, 2021 ), blood-brain barrier function ( Wevers and de Vries, 2016 ; Abdullahi et al, 2017a , 2017b ; Petersen et al, 2021 ), and cell death ( Hart et al, 2020 ). Mouse BMP2-10 are broadly distributed across the brain, while BMP11-15 has not been well studied ( Jensen et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of BMP, Wnt, and Insulin Signaling in Fragile X Syndrome

Song

Broadie²

2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Drosophila models of neurological disease contribute tremendously to research progress due to the high conservation of human disease genes, the powerful and sophisticated genetic toolkit, and the rapid generation time. Fragile X syndrome (FXS) is the most prevalent heritable cause of intellectual disability and autism spectrum disorders, and the Drosophila FXS disease model has been critical for the genetic screening discovery of new intercellular secretion mechanisms. Here, we focus on the roles of three major signaling pathways: BMP, Wnt, and insulin-like peptides. We present Drosophila FXS model defects compared to mouse models in stem cells/embryos, the glutamatergic neuromuscular junction (NMJ) synapse model, and the developing adult brain. All three of these secreted signaling pathways are strikingly altered in FXS disease models, giving new mechanistic insights into impaired cellular outcomes and neurological phenotypes. Drosophila provides a powerful genetic screening platform to expand understanding of these secretory mechanisms and to test cellular roles in both peripheral and central nervous systems. The studies demonstrate the importance of exploring broad genetic interactions and unexpected regulatory mechanisms. We discuss a number of research avenues to pursue BMP, Wnt, and insulin signaling in future FXS investigations and the development of potential therapeutics.

show abstract

“…Moreover, Bmpr1a , an essential receptor regulating downstream BMP signaling, is among the upregulated genes in both PVALB and SST lineages upon rhEPO ( Figure 2C ). Of note, recent genetic experiments have illustrated that Bmpr1a guides specific synaptic connectivity in PVALB interneurons 50,51 . In addition, we found few other genes with opposite trend of differential expression between sister lineages, also associated with synaptic pruning and maturation of interneurons.…”

Section: Resultsmentioning

confidence: 99%

Erythropoietin restrains the inhibitory potential of interneurons in the mouse hippocampus

Curto,

Carceller,

Klimczak

et al. 2023

Preprint

View full text Add to dashboard Cite

SummaryErythropoietin (EPO) aids in rectifying hippocampal transcriptional networks and synaptic structures of pyramidal lineages, thereby mitigating mood and cognition-associated disorders. An imminent conundrum is how EPO restores synapses by involving interneurons. By analyzing ∼ 12,000 single-nuclei transcriptomic data, we generated a comprehensive molecular atlas of hippocampal interneurons, resolved into 15 interneuron subtypes. Next, we studied molecular alterations upon recombinant human (rh)EPO and saw that gene expression changes relate to synaptic structure, trans-synaptic signaling and intracellular catabolic pathways. Putative ligand-receptor interactions between pyramidal and inhibitory neurons, regulating synaptogenesis, are altered upon rhEPO. An array ofin/ex vivoexperiments confirms that specific interneuronal populations exhibit reduced dendritic complexity, synaptic connectivity, and changes in plasticity-related molecules. Metabolism and inhibitory potential of interneuron subgroups are compromised, leading to greater excitability of pyramidal neurons. To conclude, improvement by rhEPO of neuropsychiatric phenotypes may partly owe to restrictive control over interneurons, facilitating re-connectivity and synapse development.

show abstract

LTP of inhibition at PV interneuron output synapses requires developmental BMP signaling

Cited by 9 publications

References 64 publications

Erythropoietin restrains the inhibitory potential of interneurons in the mouse hippocampus

Erythropoietin restrains the inhibitory potential of interneurons in the mouse hippocampus

Dysregulation of BMP, Wnt, and Insulin Signaling in Fragile X Syndrome

Erythropoietin restrains the inhibitory potential of interneurons in the mouse hippocampus

Contact Info

Product

Resources

About