Molecular and cellular rhythms in excitatory and inhibitory neurons in the mouse prefrontal cortex
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ABSTRACT:
PROVIDER: PRJNA1214766 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR32094400_1.fastq.gz | Fastqsanger.gz | |||
| SRR32094400_2.fastq.gz | Fastqsanger.gz | |||
| SRR32094401_1.fastq.gz | Fastqsanger.gz | |||
| SRR32094401_2.fastq.gz | Fastqsanger.gz | |||
| SRR32094402_1.fastq.gz | Fastqsanger.gz |
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Project description:While studies have shown that there are rhythms in gene expression in the prefrontal cortex (PFC), the contribution of different cell types and potential variation by sex has not been determined. Of particular interest are excitatory pyramidal cells and inhibitory parvalbumin (PV) interneurons, as interactions between these cell types are essential for maintaining the excitation/inhibition balance. Here, we identify cell-type specific rhythms in the translatome of PV and pyramidal cells in the mouse PFC and assess rhythms in PV cell electrophysiology. We find that while core molecular clock genes are conserved and synchronized between cell types, pyramidal cells have nearly twice as many rhythmic transcripts as PV cells (35% vs. 18%). Rhythmic transcripts in pyramidal cells also show a high degree of overlap between sexes, whereas in PV cells, rhythmic transcripts are largely distinct between sexes. Additionally, we find sex-specific effects of phase on action potential properties in PV cells. This study demonstrates that rhythms in gene expression and electrophysiological properties in the PFC vary by both cell type and sex. Moreover, the biological processes associated with rhythmic transcripts may provide insight into the unique functions of rhythms in these cells, as well as their selective vulnerabilities to circadian disruption.
2025-01-27 | GSE287818 | GEO
Project description:Comparative transcriptomic rhythms in the mouse and human prefrontal cortex
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Project description:Alterations in multiple subregions of the human prefrontal cortex (PFC) have been heavily implicated in psychiatric diseases. Moreover, emerging evidence suggests that circadian rhythms in gene expression are present across the brain, including in the PFC, and that these rhythms are altered in disease. However, investigation into the potential circadian mechanisms underlying these diseases in animal models must contend with the fact that the human PFC is highly evolved and specialized relative to that of rodents. Here, we use RNA sequencing to lay the groundwork for translational studies of molecular rhythms through a sex-specific, cross species comparison of transcriptomic rhythms between the mouse medial PFC (mPFC) and two subregions of the human PFC, the anterior cingulate cortex (ACC) and the dorsolateral PFC (DLPFC). We find that while circadian rhythm signaling is conserved across species and subregions, there is a phase shift in the expression of core clock genes between the mouse mPFC and human PFC subregions that differs by sex. Furthermore, we find that the identity of rhythmic transcripts is largely unique between the mouse mPFC and human PFC subregions, with the most overlap (20%, 236 transcripts) between the mouse mPFC and the human ACC in females. Nevertheless, we find that basic biological processes are enriched for rhythmic transcripts across species, with key differences between regions and sexes. Together, this work highlights both the evolutionary conservation of transcriptomic rhythms and the advancement of the human PFC, underscoring the importance of considering cross-species differences when using animal models.
2025-02-01 | GSE284053 | GEO
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2023-10-24 | PXD041332 | Pride
Project description:Previous studies have shown that there are rhythms in gene expression in the mouse prefrontal cortex (PFC); however, the contribution of different cell types and potential variation by sex has not yet been determined. Of particular interest are excitatory pyramidal cells and inhibitory parvalbumin (PV) interneurons, as interactions between these cell types are essential for regulating the excitation/inhibition balance and controlling many of the cognitive functions regulated by the PFC. In this study, we identify cell-type specific rhythms in the translatome of PV and pyramidal cells in the mouse PFC and assess diurnal rhythms in PV cell electrophysiological properties. We find that while core molecular clock genes are conserved and synchronized between cell types, pyramidal cells have nearly twice as many rhythmic transcripts as PV cells (35% vs. 18%). Rhythmic transcripts in pyramidal cells also show a high degree of overlap between sexes, both in terms of which transcripts are rhythmic and in the biological processes associated with them. Conversely, in PV cells, rhythmic transcripts from males and females are largely distinct. Moreover, we find sex-specific effects of phase on action potential properties in PV cells that are eliminated by environmental circadian disruption. Together, this study demonstrates that rhythms in gene expression and electrophysiological properties in the mouse PFC vary by both cell type and sex. Moreover, the biological processes associated with these rhythmic transcripts may provide insight into the unique functions of rhythms in these cells, as well as their selective vulnerabilities to circadian disruption.
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Project description:The cerebral cortex is a cellularly-complex structure comprised of a rich diversity of neuronal and glial cell types. Cortical neurons can be broadly categorized into two classes—glutamatergic excitatory neurons and GABAergic inhibitory interneurons. Previous developmental studies in rodents have led to the prevailing model that while excitatory neurons are born from progenitors located in the cortex, cortical interneurons are born from a separate population of progenitors located outside of the developing cortex in the ganglionic eminences1-5. However, the developmental potential of human cortical progenitors has not been thoroughly explored. Here we show that in addition to excitatory neurons and glia, human cortical progenitors are also capable of producing GABAergic neurons with the transcriptional characteristics and morphologies of cortical interneurons. By developing a cellular barcoding tool called “ScRNAseq-compatible Tracer for Identifying Clonal Relationships” (STICR), we were able to perform clonal lineage tracing of 1912 primary human cortical progenitors from six specimens and capture both the transcriptional identities and clonal relationships of their resulting progeny. A subpopulation of cortically-born GABAergic neurons were transcriptionally similar to cortical interneurons born from the caudal ganglionic eminence and these cells were frequently related to excitatory neurons and glia. Thus, our results demonstrate that individual human cortical progenitors can generate both excitatory neurons and cortical interneurons, providing a new framework for understanding the origins of neuronal diversity in the human cortex.
2021-11-06 | GSE187875 | GEO
Project description:Df(h15q13)/+ mouse model reveals loss of astrocytes and synaptic-related changes of the excitatory and inhibitory circuits in the medial prefrontal cortex.
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Project description:Training-induced excitatory synaptogenesis in a prefrontal cortex circuit is required for effort/reward evaluation
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Project description:Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder with a rising prevalence and genetic and environmental etiologies. Symptoms include deficits in social communication, repetitive patterns of behavior, and cognitive impairment. Neuroanatomic and biochemical investigations involve many brain areas with imbalance between glutamatergic and inhibitory neurotransmitters. We hypothesized that investigation of the synaptic compartment of the dorsolateral prefrontal cortex may provide proteomics signatures that may identify the biological underpinnings of cognitive deficits in childhood ASD. Subcellular fractionation of the synaptoneurosomes from Brodmann area 9 of a well- characterized age- and postmortem-interval-matched samples from children and adults with idiopathic ASD vs. healthy controls, were subjected to HPLC–tandem mass spectrometry and proteomic analysis.
2025-05-06 | PXD048017 | Pride
Project description:Background: The prefrontal cortex is important in regulating sleep and mood. Diurnally regulated genes in the prefrontal cortex may be controlled by the circadian system, by the sleep-wake states, or by cellular metabolism or environmental responses. Bioinformatics analysis of these genes will provide insights into a wide-range of pathways that are involved in the pathophysiology of sleep disorders and psychiatric disorders with sleep disturbances. Results: We examined gene expression in the mouse prefrontal cortex at four time points during the 24-hour (12-hour light:12-hour dark) cycle by microarrays, and identified 3,890 transcripts corresponding to 2,927 genes with diurnally regulated expression patterns. We show that 16% of the genes identified in our study are orthologs of identified clock, clock controlled or sleep/wakefulness induced genes in the mouse liver and SCN, rat cortex and cerebellum, or Drosophila head. The diurnal expression patterns were confirmed in 16 out of 18 genes in an independent set of RNA samples. The diurnal genes fall into eight temporal categories with distinct functional attributes, as assessed by the Gene Ontology classification and by the analysis of enriched transcription factor binding sites. Conclusions: Our analysis demonstrates that ~10% of transcripts have diurnally regulated expression patterns in the mouse prefrontal cortex. Functional annotation of these genes will be important for the selection of candidate genes for behavioural mutants in the mouse and for genetic studies of disorders associated with anomalies in the sleep:wake cycle and circadian rhythms. Experiment Overall Design: Prefrontal cortex from 3 biological replicates of C57BL/6J mice at four Zeitgeber Times (ZT 3, 9, 15, and 21) were analyzed
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