GABA uptake-dependent Ca
            <sup>2+</sup>
            signaling in developing olfactory bulb astrocytes

Doengi, Michael; Hirnet, Daniela; Coulon, Philippe; Pape, Hans‐Christian; Deitmer, Joachim W.; Lohr, Christian

doi:10.1073/pnas.0809513106

Cited by 109 publications

(116 citation statements)

References 41 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…Activation of Ca 2+ transients in astrocytes of the somatosensory cortex and the olfactory bulb in vivo by stimulation of afferents was accompanied by vasodilation and an increase in blood flow (23,39,40). In brain-slice preparations, the situation appears more complicated, and both vasodilation and vasoconstriction could be measured (39,41,42), depending on the metabolic state of the tissue and the amplitude of astrocytic Ca 2+ transients (43,44). In all studies mentioned above, glial cells are located in the neuropil and couple neuronal activity to responses of the vasculature via detection of synaptically released neurotransmitters.…”

Section: Discussionmentioning

confidence: 99%

Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling

Thyssen

Hirnet

Wolburg

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Neurotransmitter release generally is considered to occur at active zones of synapses, and ectopic release of neurotransmitters has been demonstrated in a few instances. However, the mechanism of ectopic neurotransmitter release is poorly understood. We took advantage of the intimate morphological and functional proximity of olfactory receptor axons and specialized glial cells, olfactory ensheathing cells (OECs), to study ectopic neurotransmitter release. Axonal stimulation evoked purinergic and glutamatergic Ca 2+ responses in OECs, indicating ATP and glutamate release. In axons expressing synapto-pHluorin, stimulation evoked an increase in synapto-pHluorin fluorescence, indicative of vesicle fusion. Transmitter release was dependent on Ca 2+ and could be inhibited by bafilomycin A1 and botulinum toxin A. Ca 2+ transients in OECs evoked by ATP, axonal stimulation, and laser photolysis of NP-EGTA resulted in constriction of adjacent blood vessels. Our results indicate that ATP and glutamate are released ectopically by vesicles along axons and mediate neurovascular coupling via glial Ca 2+ signaling.neuron-glia interactions | olfactory bulb | olfactory ensheathing cells | purinergic signaling I n the conventional view, a neuron is divided into morphologically and functionally distinct compartments, comprising dendrites receiving synaptic input, axons conducting information via action potentials, and synaptic terminals transmitting information by neurotransmitter release. Recent evidence, however, indicates that neurotransmitters also can be released along axons (e.g., in optic nerve, olfactory nerve and corpus callosum) (1-4). Axonal neurotransmitter release may include the cotransmitter ATP, which is coreleased with glutamate from axons in optic and olfactory nerves (1, 2). However, the mechanisms of this ectopic neurotransmitter release, and in particular the mechanism of neuronal ATP release, are controversial. Early studies suggested vesicular release of ATP at varicosities of peripheral nerves such as the vagus and enteric nerves (5). In few instances, vesicular ATP release could be demonstrated at central synapses (6, 7), and a vesicular ATP transporter has been described recently (8). However, other studies question the hypothesis of vesicular ATP release. Release of ATP from peripheral nerves, for example, is affected differently by presynaptic modulation than is the release of vesicular noradrenaline (9), and suppressing vesicular release with botulinum toxin and tetanus toxin does not inhibit ATP release from cholinergic synaptosomes (10, 11). Alternative modes of ATP release include pores formed by gap junctional hemichannels or P2X7 purinoceptors (12)(13)(14). Recent data demonstrate axonal ATP release from cultured neurons through volume-regulated anion channels (VRAC) upon electrical stimulation (15). To date, it is unknown which mechanisms mediate ectopic ATP release in axon tracts such as optic and olfactory nerves.The main targets of axonal neurotransmitter release are glial cell receptors, and f...

show abstract

Section: Discussionmentioning

confidence: 99%

Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling

Thyssen

Hirnet

Wolburg

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…For calcium imaging in astrocytes, we incubated brain slices with 2 μM Fluo-4 AM (Invitrogen) in standard ACSF for 20-40 min at room temperature [22]. For calcium imaging in mitral cell dendrites, 50 μM Fluo-8 (AAT Bioquest, Sunnyvale, CA, USA) was included in the pipette solution, and EGTA was omitted.…”

Section: Confocal Calcium Imagingmentioning

confidence: 99%

P2Y1 receptor activation by photolysis of caged ATP enhances neuronal network activity in the developing olfactory bulb

Fischer

Rotermund

Lohr

et al. 2011

Purinergic Signalling

Self Cite

View full text Add to dashboard Cite

It has recently been shown that adenosine-5′-triphosphate (ATP) is released together with glutamate from sensory axons in the olfactory bulb, where it stimulates calcium signaling in glial cells, while responses in identified neurons to ATP have not been recorded in the olfactory bulb yet. We used photolysis of caged ATP to elicit a rapid rise in ATP and measured whole-cell current responses in mitral cells, the output neurons of the olfactory bulb, in acute mouse brain slices. Wide-field photolysis of caged ATP evoked an increase in synaptic inputs in mitral cells, indicating an ATP-dependent increase in network activity. The increase in synaptic activity was accompanied by calcium transients in the dendritic tuft of the mitral cell, as measured by confocal calcium imaging. The stimulating effect of ATP on the network activity could be mimicked by photo release of caged adenosine 5′-diphosphate, and was inhibited by the P2Y 1 receptor antagonist MRS 2179. Local photolysis of caged ATP in the glomerulus innervated by the dendritic tuft of the recorded mitral cell elicited currents similar to those evoked by wide-field illumination. The results indicate that activation of P2Y 1 receptors in the glomerulus can stimulate network activity in the olfactory bulb.

show abstract

“…The goal of this study is to determine how Cx-mediated intercellular communication in astrocytes is organized and modulated in this brain structure characterized by functional units. Features of OG astrocytes studied so far include their morphology (7,8), membrane currents (9,10), and contribution to hemodynamic responses (11)(12)(13). Here, we report that in the glomerular layer (GL), astroglial morphologies and Cx expression patterns lead to a gap junctional communication (GJC) favored within individual OG.…”

mentioning

confidence: 99%

Plasticity of astroglial networks in olfactory glomeruli

Roux

Benchenane

Rothstein

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

117

118

View full text Add to dashboard Cite

Several recent findings have shown that neurons as well as astrocytes are organized into networks. Indeed, astrocytes are interconnected through connexin-formed gap junction channels allowing exchanges of ions and signaling molecules. The aim of this study is to characterize astrocyte network properties in mouse olfactory glomeruli where neuronal connectivity is highly ordered. Dyecoupling experiments performed in olfactory bulb acute slices (P16-P22) highlight a preferential communication between astrocytes within glomeruli and not between astrocytes in adjacent glomeruli. Such organization relies on the oriented morphology of glomerular astrocytes to the glomerulus center and the enriched expression of two astroglial connexins (Cx43 and Cx30) within the glomeruli. Glomerular astrocytes detect neuronal activity showing membrane potential fluctuations correlated with glomerular local field potentials. Accordingly, gap junctional coupling of glomerular networks is reduced when neuronal activity is silenced by TTX treatment or after early sensory deprivation. Such modulation is lost in Cx30 but not in Cx43 KO mice, indicating that Cx30-formed channels are the molecular targets of this activity-dependent modulation. Extracellular potassium is a key player in this neuroglial interaction, because (i) the inhibition of dye coupling observed in the presence of TTX or after sensory deprivation is restored by increasing [K + ] e and (ii) treatment with a K ir channel blocker inhibits dye spread between glomerular astrocytes. Together, these results demonstrate that extracellular potassium generated by neuronal activity modulates Cx30-mediated gap junctional communication between glomerular astrocytes, indicating that strong neuroglial interactions take place at this first relay of olfactory information processing.O lfactory glomeruli (OG) represent functional units where olfactory signals are first processed (1, 2). The combination of the anatomical organization and the functional activity results in a highly ordered spatial map of glomerular activation associated with each odor (3, 4). However, this well-described organization refers only to neuronal circuits, and information concerning astroglial connectivity is lacking. In the brain, astrocytes express the highest rate of connexins (Cxs), the protein constituents of gap junction channels that provide the molecular basis for direct cellto-cell communication. Though astrocytes were initially thought to form a glial syncitium, there is now evidence for a more specialized network organization (5). As increasing evidence argues for dynamic interactions between neurons and astrocytes (6), a coordinated population of astrocytes working in concert with neurons could contribute to sensory integration occurring in OG. The goal of this study is to determine how Cx-mediated intercellular communication in astrocytes is organized and modulated in this brain structure characterized by functional units. Features of OG astrocytes studied so far include their morphology (7,8), membrane...

show abstract

GABA uptake-dependent Ca ²⁺ signaling in developing olfactory bulb astrocytes

Cited by 109 publications

References 41 publications

Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling

Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling

P2Y1 receptor activation by photolysis of caged ATP enhances neuronal network activity in the developing olfactory bulb

Plasticity of astroglial networks in olfactory glomeruli

Contact Info

Product

Resources

About

GABA uptake-dependent Ca 2+ signaling in developing olfactory bulb astrocytes

Cited by 109 publications

References 41 publications

Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling

Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling

P2Y1 receptor activation by photolysis of caged ATP enhances neuronal network activity in the developing olfactory bulb

Plasticity of astroglial networks in olfactory glomeruli

Contact Info

Product

Resources

About

GABA uptake-dependent Ca ²⁺ signaling in developing olfactory bulb astrocytes