EIF2α pathway controls memory consolidation via excitatory and somatostatin inhibitory neurons
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA640593 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12053900_1.fastq.gz | Fastqsanger.gz | |||
| SRR12053900_2.fastq.gz | Fastqsanger.gz | |||
| SRR12053901_1.fastq.gz | Fastqsanger.gz | |||
| SRR12053901_2.fastq.gz | Fastqsanger.gz | |||
| SRR12053902_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:To study the impact of p-eIF2α reduction in excitatory neurons on translational landscape, we performed both excitatory neuron-specific translational profiling and general proteomic analysis in the dorsal hippocampus of eIF2α cKICaMKIIα and control mice under basal conditions and following learning.
2020-09-22 | GSE152825 | GEO
Project description:An important tenet of learning and memory is the notion of a molecular switch that promotes the formation of long-term memory1-4. The regulation of proteostasis is a critical and rate-limiting step in the consolidation of new memories5-10. One of the most effective and prevalent ways to enhance memory is by regulating the synthesis of proteins controlled by the translation initiation factor eIF211. Phosphorylation of the α-subunit of eIF2 (p-eIF2α), the central component of the integrated stress response (ISR), impairs long-term memory formation in rodents and birds11-13. By contrast, inhibiting the ISR by mutating the eIF2α phosphorylation site, genetically11 and pharmacologically inhibiting the ISR kinases14-17, or mimicking reduced p-eIF2α with the ISR inhibitor ISRIB11, enhances long-term memory in health and disease18. Here we used molecular genetics to dissect the neuronal circuits by which the ISR gates cognitive processing. We found that learning reduces eIF2α phosphorylation in hippocampal excitatory neurons and a subset of hippocampal inhibitory neurons (those that express somatostatin, but not parvalbumin). Moreover, ablation of p-eIF2α in either excitatory or somatostatin-expressing (but not parvalbumin-expressing) inhibitory neurons increased general mRNA translation, bolstered synaptic plasticity and enhanced long-term memory. Thus, eIF2α-dependent mRNA translation controls memory consolidation via autonomous mechanisms in excitatory and somatostatin-expressing inhibitory neurons.
| S-EPMC7874887 | biostudies-literature
Project description:Anxiety is elicited by excessive apprehension about unpredictable threats. However, the neural circuit governing unpredictable threat induced anxiety remains unclear. Here, we found ventral bed nucleus of the stria terminalis (vBNST) GABAergic neurons displayed selective activation to unpredictable threats by means ofthrough coordinated excitatory input from insular cortex (IC) glutamergic neurons and inhibitory input from lateral nucleus of the amygdala (CeL) somatostatin (SOM) neurons. Using activity-dependent neuronal tagging technology, we found that unpredictable threat responsive cells in vBNST drive freezing and anxiety via projections to ventral lateral periaqueductal grey (vlPAG) and median nucleus of the amygdala (CeM) respectively. Finally, we identified KCNQ3 plays an essential role in hyperactivity of vBNST GABAergic neurons and induced anxiety. These data identified a forward inhibitory circuit that determine the selective activation of vBNST in unpredictable threat and anxiety, and suggest that Kcnq3 KCNQ3 channel acts as a promising target in treatment of anxiety disorder following unpredictable stress.
2024-02-19 | GSE255670 | GEO
Project description:The proper balance of excitatory and inhibitory neurons is crucial to normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors, Ascl1 and Ptf1a, are essential for generating the correct number and sub-type of neurons in multiple regions of the nervous system. M-BM- In the dorsal spinal cord, Ascl1 and Ptf1a have contrasting functions in specifying inhibitory versus excitatory neurons. To understand how Ascl1 and Ptf1a function in these processes, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a regulate the specification of excitatory and inhibitory neurons in the dorsal spinal cord through direct regulation of distinct homeodomain transcription factors known for their function in neuronal sub-type specification. Besides their roles in regulating these homeodomain factors, Ascl1 and Ptf1a each function differently during neuronal development with Ascl1 directly regulating genes with roles in several steps of the neurogenic program including, Notch signaling, neuronal differentiation, axon guidance, and synapse formation. In contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Examination of the Ascl1 and Ptf1a bound sequences shows they are enriched for a common E-Box with a GC core and with additional motifs used by Sox, Rfx, Pou, and Homeodomain factors. Ptf1a bound sequences are uniquely enriched in an E-Box with a GA/TC core and in the binding motif for its co-factor Rbpj, providing two keys to specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding for how they function in neuronal development, particularly as key regulators of homeodomain transcription factors required for neuronal sub-type specification. Examination of gene expression in Ascl1 and Ptf1a lineage cells in the developing neural tube.
2014-06-13 | E-GEOD-55831 | biostudies-arrayexpress
Project description:The proper balance of excitatory and inhibitory neurons is crucial to normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors, Ascl1 and Ptf1a, are essential for generating the correct number and sub-type of neurons in multiple regions of the nervous system. M-BM- In the dorsal spinal cord, Ascl1 and Ptf1a have contrasting functions in specifying inhibitory versus excitatory neurons. To understand how Ascl1 and Ptf1a function in these processes, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a regulate the specification of excitatory and inhibitory neurons in the dorsal spinal cord through direct regulation of distinct homeodomain transcription factors known for their function in neuronal sub-type specification. Besides their roles in regulating these homeodomain factors, Ascl1 and Ptf1a each function differently during neuronal development with Ascl1 directly regulating genes with roles in several steps of the neurogenic program including, Notch signaling, neuronal differentiation, axon guidance, and synapse formation. In contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Examination of the Ascl1 and Ptf1a bound sequences shows they are enriched for a common E-Box with a GC core and with additional motifs used by Sox, Rfx, Pou, and Homeodomain factors. Ptf1a bound sequences are uniquely enriched in an E-Box with a GA/TC core and in the binding motif for its co-factor Rbpj, providing two keys to specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding for how they function in neuronal development, particularly as key regulators of homeodomain transcription factors required for neuronal sub-type specification. Examination of Ascl1 and Ptf1a genome-wide binding in developing neural tube.
2014-06-13 | E-GEOD-55840 | biostudies-arrayexpress
Project description:Benzodiazepine (BZ) drugs treat seizures, anxiety, insomnia, and alcohol withdrawal by potentiating γ2 subunit containing GABA type A receptors (GABAARs). BZ clinical use is hampered by tolerance and withdrawal symptoms, which include heightened seizure susceptibility, panic, and sleep disturbances. Here, we undergo a comprehensive investigation of inhibitory GABAergic and excitatory glutamatergic plasticity in mice tolerant to benzodiazepine sedation. Using quantitative proteomics approaches, we reveal cortex neuroadaptations of key pro-excitatory mediators and synaptic plasticity pathways, highlighted by Ca2+/calmodulin-dependent protein kinase II (CAMKII), MAPK, and PKC signaling.
2023-10-24 | PXD041332 | Pride
Project description:We used a psd95-GFP cre dependent KI mouse to label PSD95 with GFP specifically in excitatory (CaMK) or inhibitory (vGAT) neurons. PSD95 was pulled down with a GFP nanobody and the resulting complex was used for massspectrometry analysis.
2023-06-03 | PXD041635 | Pride
Project description:Coordinated excitatory and inhibitory circuits governing unpredictable threat induced anxiety
| PRJNA1076124 | ENA
Project description:Individual Human Cortical Progenitors Can Produce Excitatory and Inhibitory Neurons
| PRJNA777693 | ENA
Project description:Recent studies have revealed an essential role for embryonic cortical development in the pathophysiology of neurodevelopmental disorders, including autism spectrum disorder (ASD). However, the genetic basis and underlying mechanisms remain unclear. Here, we generate mutant human embryonic stem cell lines (Mut hESCs) carrying an NR2F1-R112K mutation that has been identified in a patient with ASD features, and investigate their neurodevelopmental alterations. Mut hESCs overproduce ventral telencephalic neuron progenitors (ventral NPCs) and inhibitory neurons, and underproduce dorsal NPCs and excitatory neurons. These alterations can be mainly attributed to the aberrantly activated Hedgehog signaling pathway. Moreover, the corresponding Nr2f1 point mutant mice display a similar excitatory/inhibitory neuron imbalance and abnormal behaviors. Antagonizing the increased inhibitory synaptic transmission partially alleviates their behavioral deficits. Together, our results suggest that the NR2F1-dependent imbalance of excitatory/inhibitory neuron differentiation caused by the activated Hedgehog pathway is one precursor of neurodevelopmental disorders and may enlighten the therapeutic approaches.
2020-04-21 | GSE132965 | GEO