Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The type 3 adenylyl cyclase is required for the survival and maturation of newly generated granule cells in the olfactory bulb.

ABSTRACT: The type 3 adenylyl cyclase (AC3) is localized to olfactory cilia in the main olfactory epithelium (MOE) and primary cilia in the adult mouse brain. Although AC3 has been strongly implicated in odor perception and olfactory sensory neuron (OSN) targeting, its role in granule cells (GCs), the most abundant interneurons in the main olfactory bulb (MOB), remains largely unknown. Here, we report that the deletion of AC3 leads to a significant reduction in the size of the MOB as well as the level of adult neurogenesis. The cell proliferation and cell cycle in the subventricular zone (SVZ), however, are not suppressed in AC3-/- mice. Furthermore, AC3 deletion elevates the apoptosis of GCs and disrupts the maturation of newly formed GCs. Collectively, our results identify a fundamental role for AC3 in the development of adult-born GCs in the MOB.

SUBMITTER: Luo J

PROVIDER: S-EPMC4373939 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The type 3 adenylyl cyclase is required for the survival and maturation of newly generated granule cells in the olfactory bulb.

Luo Jie J Chen Xuanmao X Pan Yung-Wei YW Lu Song S Xia Zhengui Z Storm Daniel R DR

PloS one 20150325 3

The type 3 adenylyl cyclase (AC3) is localized to olfactory cilia in the main olfactory epithelium (MOE) and primary cilia in the adult mouse brain. Although AC3 has been strongly implicated in odor perception and olfactory sensory neuron (OSN) targeting, its role in granule cells (GCs), the most abundant interneurons in the main olfactory bulb (MOB), remains largely unknown. Here, we report that the deletion of AC3 leads to a significant reduction in the size of the MOB as well as the level of ...[more]

PMID: 25807252

Similar Datasets

Maturation of postnatally generated olfactory bulb granule cells depends on functional γ-protocadherin expression.

Project description:γ-protocadherins (γ-pcdhs) are transmembrane receptor proteins ubiquitously expressed in the postnatal and adult mouse brain. γ-pcdhs are required for normal neuronal development as shown for spinal cord interneurons, retinal ganglion cells and cortical neurons. To test the role of γ-pcdhs during development of subventricular zone progenitor cells and their subsequent differentiation into olfactory granule cells we generated a conditional γ-pcdh(lox/lox) allele (γ-pcdh(lox/lox)) allowing for functional γ-pcdh inactivation upon lentivirus-mediated Cre-recombinase expression selectively in subventricular zone progenitor cells. While γ-pcdh loss did not alter the proliferation of subventricular zone progenitors, γ-pcdh ko progenitors that reached the main olfactory bulb showed a significant reduction in dendritic arborization and failed to develop dendritic spines. Our results suggest that olfactory bulb granule cell maturation necessitates functional γ-pcdh expression.

| S-EPMC3604712 | biostudies-literature

Activity Dependent Modulation of Granule Cell Survival in the Accessory Olfactory Bulb at Puberty.

Project description:The vomeronasal system (VNS) is specialized in the detection of salient chemical cues triggering social and neuroendocrine responses. Such responses are not always stereotyped, instead, they vary depending on age, sex, and reproductive state, yet the mechanisms underlying this variability are unclear. Here, by analyzing neuronal survival in the first processing nucleus of the VNS, namely the accessory olfactory bulb (AOB), through multiple bromodeoxyuridine birthdating protocols, we show that exposure of female mice to male soiled bedding material affects the integration of newborn granule interneurons mainly after puberty. This effect is induced by urine compounds produced by mature males, as bedding soiled by younger males was ineffective. The granule cell increase induced by mature male odor exposure is not prevented by pre-pubertal ovariectomy, indicating a lesser role of circulating estrogens in this plasticity. Interestingly, the intake of adult male urine-derived cues by the female vomeronasal organ increases during puberty, suggesting a direct correlation between sensory activity and AOB neuronal plasticity. Thus, as odor exposure increases the responses of newly born cells to the experienced stimuli, the addition of new GABAergic inhibitory cells to the AOB might contribute to the shaping of vomeronasal processing of male cues after puberty. Consistently, only after puberty, female mice are capable to discriminate individual male odors through the VNS.

| S-EPMC5440572 | biostudies-literature

Genetic Increases in Olfactory Bulb BDNF Do Not Enhance Survival of Adult-Born Granule Cells.

Project description:Adult-born neurons produced in the dentate gyrus subgranular zone (SGZ) develop as excitatory hippocampal granule cells (GCs), while those from the subventricular zone (SVZ) migrate to the olfactory bulb (OB), where most develop as GABAergic olfactory GCs. Both types of neurons express TrkB as they mature. Normally ~50% of new olfactory GCs survive, but survival declines if sensory drive is reduced. Increases in endogenous brain-derived neurotrophic factor (BDNF) in hippocampus, particularly with wheel running, enhance dentate GC survival. Whether survival of new olfactory GCs is impacted by augmenting BDNF in the OB, where they mature and integrate, is not known. Here, we determined if increasing OB BDNF expression enhances survival of new GCs, and if it counters their loss under conditions of reduced sensory activity. Neurogenesis was assessed under normal conditions, and following unilateral naris occlusion, in mice overexpressing BDNF in the granule cell layer (GCL). OB BDNF levels were significantly higher in transgenic mice compared to controls, and this was maintained following sensory deprivation. Bromodeoxyuridine (BrdU) cell birth dating showed that at 12-14 days post-BrdU, numbers of new GCs did not differ between genotypes, indicating normal recruitment to the OB. At later intervals, transgenic and control mice showed levels of GC loss in deprived and nondeprived animals that were indistinguishable, as was the incidence of apoptotic cells in the GCL. These results demonstrate that, in contrast to new dentate GCs, elevations in endogenous BDNF do not enhance survival of adult-born olfactory GCs.

| S-EPMC6923167 | biostudies-literature

Lateral dispersion is required for circuit integration of newly generated dentate granule cells.

Project description:The process of circuit integration of newly-generated dentate granule cells of the hippocampus has been presumed to be a dynamic process. In fact, little is known regarding the initial development of newly generated neurons prior to circuit integration and the significance of this stage for circuit integration. Here, using advanced live imaging methods, we systematically analyze the dynamic dispersion of newly generated neurons in the neurogenic zone and observe that cells that are physically adjacent coordinate their lateral dispersion. Whole-cell recordings of adjacent newly generated neurons reveal that they are coupled via gap junctions. The dispersion of newly generated cells in the neurogenic zone is restricted when this coupling is disrupted, which severely impairs their subsequent integration into the hippocampal circuit. The results of this study reveal that the dynamic dispersion of newly generated dentate granule cells in the neurogenic zone is a required developmental stage for circuit integration.

| S-EPMC6658520 | biostudies-literature

Disruption of centrifugal inhibition to olfactory bulb granule cells impairs olfactory discrimination.

Project description:Granule cells (GCs) are the most abundant inhibitory neuronal type in the olfactory bulb and play a critical role in olfactory processing. GCs regulate the activity of principal neurons, the mitral cells, through dendrodendritic synapses, shaping the olfactory bulb output to other brain regions. GC excitability is regulated precisely by intrinsic and extrinsic inputs, and this regulation is fundamental for odor discrimination. Here, we used channelrhodopsin to stimulate GABAergic axons from the basal forebrain selectively and show that this stimulation generates reliable inhibitory responses in GCs. Furthermore, selective in vivo inhibition of GABAergic neurons in the basal forebrain by targeted expression of designer receptors exclusively activated by designer drugs produced a reversible impairment in the discrimination of structurally similar odors, indicating an important role of these inhibitory afferents in olfactory processing.

| S-EPMC3767551 | biostudies-literature

Disinhibition of olfactory bulb granule cells accelerates odour discrimination in mice.

Project description:Granule cells are the dominant cell type of the olfactory bulb inhibiting mitral and tufted cells via dendrodendritic synapses; yet the factors regulating the strength of their inhibitory output, and, therefore, their impact on odour discrimination, remain unknown. Here we show that GABAAR β3-subunits are distributed in a somatodendritic pattern, mostly sparing the large granule cell spines also known as gemmules. Granule cell-selective deletion of β3-subunits nearly abolishes spontaneous and muscimol-induced currents mediated by GABAA receptors in granule cells, yet recurrent inhibition of mitral cells is strongly enhanced. Mice with disinhibited granule cells require less time to discriminate both dissimilar as well as highly similar odourants, while discrimination learning remains unaffected. Hence, granule cells are controlled by an inhibitory drive that in turn tunes mitral cell inhibition. As a consequence, the olfactory bulb inhibitory network adjusts the speed of early sensory processing.

| S-EPMC4673882 | biostudies-literature

Adenylyl cyclase 5-generated cAMP controls cerebral vascular reactivity during diabetic hyperglycemia.

Project description:Elevated blood glucose (hyperglycemia) is a hallmark metabolic abnormality in diabetes. Hyperglycemia is associated with protein kinase A (PKA)-mediated stimulation of L-type Ca2+ channels in arterial myocytes resulting in increased vasoconstriction. However, the mechanisms by which glucose activates PKA remain unclear. Here, we showed that elevating extracellular glucose stimulates cAMP production in arterial myocytes, and that this was specifically dependent on adenylyl cyclase 5 (AC5) activity. Super-resolution imaging suggested nanometer proximity between subpopulations of AC5 and the L-type Ca2+ channel pore-forming subunit CaV1.2. In vitro, in silico, ex vivo and in vivo experiments revealed that this close association is critical for stimulation of L-type Ca2+ channels in arterial myocytes and increased myogenic tone upon acute hyperglycemia. This pathway supported the increase in L-type Ca2+ channel activity and myogenic tone in two animal models of diabetes. Our collective findings demonstrate a unique role for AC5 in PKA-dependent modulation of L-type Ca2+ channel activity and vascular reactivity during acute hyperglycemia and diabetes.

| S-EPMC6668679 | biostudies-literature

Adenylyl cyclase 6 is required for maintaining acid-base homeostasis.

Project description:Adenylyl cyclase (AC) isoform 6 (AC6) is highly expressed throughout the renal tubule and collecting duct (CD), catalyzes the synthesis of cAMP and contributes to various aspects of renal transport. Several proteins involved in acid-base homeostasis are regulated by cAMP. In the present study, we assess the relative contribution of AC6 to overall acid-base regulation using mice with global deletion of AC6 (AC6-/-) or newly generated mice lacking AC6 in the renal tubule and CD (AC6loxloxPax8Cre). Higher energy expenditure in AC6-/- relative to wild-type (WT) mice, was associated with lower urinary pH, mild alkalosis in conjunction with elevated blood HCO3- concentrations, and significantly higher renal abundance of the H+-ATPase B1 subunit. In contrast with WT mice, AC6-/- mice have a less pronounced increase in urinary pH after 8 days of HCO3- challenge, which is associated with increased blood pH and HCO3- concentrations. Immunohistochemistry demonstrated that AC6 was expressed in intercalated cells (IC), but subcellular distribution of the H+-ATPase B1 subunit, pendrin, and the anion exchangers 1 and 2 in AC6-/- mice was normal. In the AC6-/- mice, H+-ATPase B1 subunit levels after HCO3- challenge were greater, which correlated with a higher number of type A IC. In contrast with the AC6-/- mice, AC6loxloxPax8Cre mice had normal urinary pH under baseline conditions but higher blood HCO3- than controls after HCO3- challenge. In conclusion, AC6 is required for maintaining normal acid-base homeostasis and energy expenditure. Under baseline conditions, renal AC6 is redundant for acid-base balance but becomes important under alkaline conditions.

| S-EPMC6512970 | biostudies-literature

<i>Tsc2</i> shapes olfactory bulb granule cell molecular and morphological characteristics.

Project description:Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations that inactivate TSC1 or TSC2. Hamartin and tuberin are encoded by TSC1 and TSC2 which form a GTPase activating protein heteromer that inhibits the Rheb GTPase from activating a growth promoting protein kinase called mammalian target of rapamycin (mTOR). Growths and lesions occur in the ventricular-subventricular zone (V-SVZ), cortex, olfactory tract, and olfactory bulbs (OB) in TSC. A leading hypothesis is that mutations in inhibitory neural progenitor cells cause brain growths in TSC. OB granule cells (GCs) are GABAergic inhibitory neurons that are generated through infancy by inhibitory progenitor cells along the V-SVZ. Removal of Tsc1 from mouse OB GCs creates cellular phenotypes seen in TSC lesions. However, the role of Tsc2 in OB GC maturation requires clarification. Here, it is demonstrated that conditional loss of Tsc2 alters GC development. A mosaic model of TSC was created by performing neonatal CRE recombinase electroporation into inhibitory V-SVZ progenitors yielded clusters of ectopic cytomegalic neurons with hyperactive mTOR complex 1 (mTORC1) in homozygous Tsc2 mutant but not heterozygous or wild type mice. Similarly, homozygous Tsc2 mutant GC morphology was altered at postnatal days 30 and 60. Tsc2 mutant GCs had hypertrophic dendritic arbors that were established by postnatal day 30. In contrast, loss of Tsc2 from mature GCs had negligible effects on mTORC1, soma size, and dendrite arborization. OB transcriptome profiling revealed a network of significantly differentially expressed genes following loss of Tsc2 during development that altered neural circuitry. These results demonstrate that Tsc2 has a critical role in regulating neural development and shapes inhibitory GC molecular and morphological characteristics.

| S-EPMC9581303 | biostudies-literature

Dopamine inhibits mitral/tufted--> granule cell synapses in the frog olfactory bulb.

Project description:Synaptic interactions between the dendrites of mitral/tufted (MT) and granule cells (GCs) in the olfactory bulb are important for the determination of spatiotemporal firing patterns of MTs, which form an odor representation passed to higher brain centers. These synapses are subject to modulation from several sources originating both within and outside the bulb. We show that dopamine, presumably released by TH-positive local interneurons, reduces synaptic transmission from MTs to GCs. MT neurons express D2-like receptors (D2Rs), and both dopamine and the D2 agonist quinpirole decrease EPSC amplitude at the MT--> GC synapse. D2R activation also increases paired pulse facilitation and decreases the frequency of action potential-independent spontaneous miniature EPSCs in GCs, consistent with an effect on MT glutamate release downstream from Ca2+ influx. Analysis of spike-evoked Ca2+ transients in MT lateral dendrites additionally shows that quinpirole reduces Ca2+ influx preferentially at distal locations, possibly by reducing dendritic excitability via increased transient K+ channel availability. When the OB is activated physiologically by using odor stimuli, blocking D2Rs increases the power of GABA(A)-dependent oscillations in the local field potential. This demonstrates a functional role for the dopaminergic circuit during normal odor-evoked responses and for the modulation of dendritic release and excitability in neuronal circuit function. Regulation of spike invasion of lateral dendrites by transient K+ currents also may provide a mechanism for local outputs of MTs to be controlled dynamically via other neuromodulators or by postsynaptic potentials.

| S-EPMC6729800 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data