Expression data from DD neurons isolated from early L1 stage C. elegans larvae.
Ontology highlight
ABSTRACT: Six DD class GABAergic neurons are generated in the embryo to synapse with ventral muscles and receive input from cholinergic neurons in the dorsal nerve cord. After hatching and toward the end of the first larval (L1) stage, DD neurons reverse polarity (i.e., synapse with dorsal muscles, receive ventral cholinergic inputs). Expression profiles were generated from DD neurons in the early L1 stage before the initiation of the remodeling program. We used microarray analysis to detect transcripts with potential roles in DD remodeling. We used FACS to isolate ttr-39::mCherry labeled DD GABAergic motor neurons from a synchronized population of L1 larvae and amplified and labeled total RNA to generate Affymetrix Genome Array data. The DD data sets were compared to an expression profile obtained from all cells in a matched population of synchronized L1 larvae. See Spencer et al. PLOS One 9, e112102 (2014).
Project description:Six DD class GABAergic neurons are generated in the embryo to synapse with ventral muscles and receive input from cholinergic neurons in the dorsal nerve cord. After hatching and toward the end of the first larval (L1) stage, DD neurons reverse polarity (i.e., synapse with dorsal muscles, receive ventral cholinergic inputs). Expression profiles were generated from DD neurons in the early L1 stage before the initiation of the remodeling program. We used microarray analysis to detect transcripts with potential roles in DD remodeling.
Project description:During development C. elegans GABAergic dorsal D-class (DD) motor neurons reverse polarity such that the axonal and dendritic compartments are switched. We found that the gene DVE-1 is important for this process. To elucidate potential targets of dve-1 transcriptional regulation we conducted bulk RNA sequencing of total RNA from early L1 stage wild type and dve-1 mutant animals
Project description:Our microarray results showed there were up-regulated 28 genes and down-regulated 29 genes, which related depression and inflammatory response such as cytokine-cytokine receptor interaction, chemokine signaling pathway, dopaminergic synapse, glutamatergic synapse, GABAergic synapse, cholinergic synapse, and serotonergic synapse. Among these genes, especially, higher hippocampal mRNA expression of transthyretin (Ttr), Zinc finger protein of the cerebellum 1 (Zic1), and Ectonucleotide pyrophosphatase/phosphodiesterase 2 (Enpp2) was found in kososan-administered defeated mice than water-administered defeated mice
Project description:Epilepsy in women is often accompanied by hormonal disturbances including irregular cycles and premature onset of menopause. Decline in estrogen levels results in increased risk for neurodegenerative diseases, with strong participation of chronic inflammation. We have shown that estradiol (EB) has neuroprotective effects against seizure-induced damage in the sensitive hilar region of hippocampal dentate gyrus associated with neuropeptide Y (NPY) upregulation. Here, we quantify the alterations caused by kainic acid-induced status epilepticus in the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic synapse transcriptomes of dentate gyrus of ovariectomized female rats and the recovery effects of the EB replacement. Our data indicate that the EB replacement reduces the number of significantly regulated genes in seizured ovariectomized female rats by about 45%. The new measure Pathway Restoration Efficiency (PRE) indicates the dopaminergic synapse to be the most protected (65%) and the GABAergic synapse the least protected (37%) by the EB replacement.
Project description:Neural networks, formed by synchronized oscillatory bursts of activity across large populations of neurons, are fundamental to human cognition and behavior, and disrupted in neurodevelopmental disorders. Yet, mechanisms driving the emergence of these rhythms, known as oscillogenesis, are not well understood, particularly in the human brain. Using multi-electrode arrays, we investigated oscillogenesis in 2D human induced pluripotent stem cell (hiPSC) cultures at different developmental stages, and under pharmacological challenges, in two models: 1) iCell GlutaNeurons (iGluta) and 2) Neurogenin-2 patterned induced neurons (NGN2-piNs). iGluta cultures exhibited nested oscillations that were reduced by GABAA receptor blockade and emerged earlier when the proportion of GABAergic neurons was increased. Furthermore, pharmacological manipulations of voltage-gated potassium (Kv) channels and cholinergic receptors modulated the pattern of nested oscillations, demonstrating the assay’s potential for drug screening and modeling network dysfunction. In contrast, NGN2-piNs exhibited only rudimentary nested oscillations that were not affected by GABAA receptor blockade, despite the presence of GABAergic neurons, and showed distinct responses to Kv channel blockade. These results reveal the capacity of these 2D cultures to model oscillogenesis, and underscore the need for their continued refinement, paving the way for linking systems-level neural networks to human cognition and disease.
Project description:Ventral subiculum (vSUB) is integral to the regulation of stress and reward, however the intrinsic connectivity and synaptic properties of the inhibitory microcircuit are poorly understood. Neurexin-3 (Nrxn3) is highly expressed in hippocampal inhibitory neurons, but its function at inhibitory synapses has remained elusive. Using slice electrophysiology, imaging, and single-cell RNA sequencing, we identify multiple roles for Nrxn3 at GABAergic parvalbumin (PV) interneuron synapses made onto vSUB regular spiking (RS) and burst spiking (BS) principal neurons. Surprisingly, we found that intrinsic connectivity of vSUB and synaptic function of Nrxn3 in vSUB are sexually dimorphic. We reveal that vSUB PVs make preferential contact with RS neurons in males, but BS neurons in females. Furthermore, we determined that despite comparable Nrxn3 isoform expression in male and female PV neurons, Nrxn3 maintains synapse density at PV-RS synapses in males, but suppresses presynaptic release at the same synapses in females.
Project description:In order to gain a greater understanding of neurotransmitter specification we profiled the transcription state of cholinergic, GABAergic and glutamatergic neurons in vivo at multiple developmental time points. We identified 86 differentially expressed transcription factors that are uniquely enriched, or uniquely depleted, in a specific neurotransmitter subtype. Some transcription factors show a similar profile across development, others only show enrichment or depletion at specific developmental stages. Profiling of acj6 (cholinergic enriched) and Ets65A (cholinergic depleted) binding sites in vivo reveals that they both directly bind the ChAT locus, in addition to a wide spectrum of other key neuronal differentiation genes.
Project description:Fetal hypoxia, characterized by reduced oxygen levels, adversely impacts fetal development and contributes to 23% of neonatal deaths worldwide. Notably, the developing brain, particularly in its immature stage, is highly susceptible to hypoxic insult, which increases the risk of neural defects, brain damage, and long-term cognitive impairments in offspring. Nevertheless, the specific cell types affected and the underlying molecular mechanisms that mediate hypoxic brain injury remain incompletely understood. In this study, we established a three-dimensional human brain organoid modeling fetal hypoxic brain injury. Utilizing single-cell transcriptomic analysis, we observed a global hypoxic response in cortical progenitors and neurons, characterized by enhanced HIF-1 signaling and increased expression of hypoxia-responsive genes following hypoxic insult. Under hypoxic conditions, glycolysis, reactive oxygen species pathway and oxidative phosphorylation were simultaneously upregulated. Furthermore, hypoxia led to a decrease in cell division and a suppression of neurotrophin signaling pathways. Regarding developmental stage, cortical progenitors exhibited minimal sensitivity to hypoxia, with ventral radial glia, outer radial glia, and intermediate progenitors (IPs) being largely unaffected. In contrast, glia progenitors displayed a slight tendency towards premature maturation. Conversely, hypoxia had a detrimental effect on the maturation of developing neurons, including glutamatergic and GABAergic neurons. Significantly, we identified two distinct populations of GABAergic neurons with differing characteristics. GABAergic neuron type 1 exhibited lower expression levels of GAD1 and GAD2 and greater resistance to hypoxia compared to GABAergic neuron type 2. Notably, GABAergic neuron type 2 was the most susceptible to hypoxia among all cell types, showing increased ferroptosis, disrupted axon development, and impaired synapse function, potentially due to decreased Hedgehog signaling. Additionally, specific responses to hypoxia in developing neurons included selective reduction in fatty acid synthesis in outer radial glia cells, glutamatergic neurons and GABAergic neuron type 1, selective downregulation of mTORC1 signaling in IPs, selective elevation of unfolded protein response in GABAergic neuron type 1, and selective activation of TNFα-signaling via NFκB in IPs, glutamatergic neurons and GABAergic neuron type 2. In summary, our study provides a comprehensive understanding of the distinct cellular responses among cortical progenitors and neurons in fetal hypoxic brain injury, providing potential therapeutic targets for this condition.