Segregated Expression of AMPA-Type Glutamate Receptors and Glutamate Transporters Defines Distinct Astrocyte Populations in the Mouse Hippocampus

Matthias, Katja; Kirchhoff, Frank; Seifert, Gerald; Hüttmann, Kerstin; Matyash, Marina; Kettenmann, Helmut; Steinhäuser, Christian

doi:10.1523/jneurosci.23-05-01750.2003

Cited by 403 publications

(503 citation statements)

References 53 publications

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“…This blockade (confirmed in Figure 1A here) does not rule out a role for other cell types (including astrocytes) in NAD(P)H responses to brief stimuli, as their activity may be a consequence of neuronal depolarization, for example, as a consequence of K + efflux after neuronal depolarization (Brookes, 2000;Orkand et al, 1966). Alternatively, activation of iGluRs localized to glia (Matthias et al, 2003) could potentially contribute to these responses. However, it does argue against a major role for glial glutamate uptake contributing to NAD(P)H transients under these conditions, as the application of iGluR blockers should not substantially diminish extracellular glutamate concentrations during stimulation.…”

Section: Glutamate Uptakementioning

confidence: 83%

NAD(P)H Fluorescence Transients after Synaptic Activity in Brain Slices: Predominant Role of Mitochondrial Function

Brennan

Connor

Shuttleworth

2006

J Cereb Blood Flow Metab

114

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Excitatory stimulation in hippocampal slices results in biphasic NAD(P)H fluorescence transients. Previous studies using differing stimulus protocols agreed that the oxidation phase is a consequence of mitochondrial metabolism, but the reduction phase has been attributed to (1) mitochondrial nicotinamide adenine dinucleotide (NADH) generation or (2) astrocytic glycolysis triggered by glutamate uptake. In an attempt to reconcile these two views, the present study examined NAD(P)H signals evoked by a wide range of stimulus durations (40 ms to 20 secs). A combination of ionotropic glutamate receptor (iGluR) antagonists (6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 2-amino-5-phosphonopentanoic acid (APV)) virtually abolished responses to brief stimuli (40 to 200 ms, 50 Hz), but a significant fraction of the signal elicited by extended stimulation (20 secs, 32 Hz) was resistant to CNQX/APV. Glycolysis was inhibited by removal of glucose and addition of 2-deoxyglucose (2DG) (10 mmol/L) or iodoacetic acid (IAA, 1 mmol/L). Pyruvate was provided as an alternative substrate for oxidative phosphorylation and the A1 receptor antagonist 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX) included to prevent decreases in synaptic efficacy. If sufficient pyruvate was supplied, responses to brief and extended stimuli were unaffected by glycolytic inhibition and not significantly reduced by an inhibitor of glucose uptake (3-O-methyl glucose, 3 mmol/L). When timed to arrive at the peak of overshoots generated by extended synaptic stimulation, brief pyruvate applications (10 mmol/L, 2 mins) had little effect on evoked NAD(P)H increases. Flavoprotein autofluorescence transients after extended stimuli matched (with inverted sign) NAD(P)H responses. Responses to extended stimuli were not reduced by a nonselective inhibitor of glutamate uptake DL-Threo-b-benzyloxyaspartic acid (TBOA). These results suggest that NAD(P)H transients report mitochondrial dynamics, rather than recruitment of glycolytic metabolism, over a wide range of stimulus intensities.

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Section: Glutamate Uptakementioning

confidence: 83%

NAD(P)H Fluorescence Transients after Synaptic Activity in Brain Slices: Predominant Role of Mitochondrial Function

Brennan

Connor

Shuttleworth

2006

J Cereb Blood Flow Metab

114

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“…77,78. However, NG2 expressing glia are distinct from OPCs or O-2A cells that give rise to oligodendrocytes during development. [79][80][81] For example, OPCs that are committed to differentiation into oligodendrocytes express the tetraspanin protein CD9, but only a minority (o1%) of adult NG2-glia express CD9. 75 Furthermore, NG2-glia in the optic nerve do not depend on axons, 80 in direct contrast to O-2A cells, which are lost following the optic nerve transection due to a 90% decrease in their proliferation.…”

Section: Atp-evoked Ca 2 þ Signalling In Physiology and Pathologymentioning

confidence: 99%

Functions of optic nerve glia: axoglial signalling in physiology and pathology

Butt

Pugh

Hubbard

et al. 2004

Eye

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An early concept of glial function envisaged them as passive and unexcitable structural elements, much like the connective tissues of organs in the periphery. It is now known that glia have a widespread range of physiological roles and react to all forms of pathological insult. This paper reviews the major functions of oligodendrocytes and astrocytes, the main types of glia in the optic nerve, and examines novel NG2-glia, otherwise known as oligodendrocyte progenitor cells (OPCs). The major function of oligodendrocytes is to produce the myelin sheaths that insulate CNS axons, but they also have important roles in the establishment of nodes of Ranvier, the sites of action potential propagation, and axonal integrity. Astrocytes have multiple physiological and pathological functions, including potassium homeostasis and metabolism, and reactive astrogliosis in response to CNS insults. The bulk of NG2-glia are postmitotic complex cells, distinct from OPCs, and respond to any insult to the CNS by a rapid and stereotypic injury response. This may be their primary unction, but NG2-glia, or a subpopulation of NG2-expressing adult OPCs, also provide remyelinating oligodendrocytes following demyelination. Oligodendrocytes, astrocytes, and NG2-glia all contact axons at nodes of Ranvier and respond to glutamate, ATP, and potassium released during axonal electrical activity. Glutamate and ATP evoke calcium signalling in optic nerve glia and have dual roles in physiology and pathology, coupling glial functions to axonal activity during normal activity, but enhanced activation induces an injury response, as seen following injury, demyelination, and ischaemia.

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“…This only occurred to a small extent in the dentate gyrus and not at all in CA1. Although glial cells in the dentate gyrus have not been specifically studied, glial cells in the hippocampus are reported to vary, with subpopulations of astrocytes reported (Matthias et al, 2003). Glial contributions to ionic regulation have also been shown to differ between CA1 and CA3.…”

Section: Discussionmentioning

confidence: 99%

Regulation of extracellular calcium in the hippocampus in vivo during epileptiform activity—Role of astrocytes

et al. 2007

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Astrocytes have been suggested to regulate the extracellular calcium concentration ([Ca 2+ ] o ), but this has not been thoroughly investigated. Adult, male Sprague-Dawley rats were used to record changes in [Ca 2+ ] o in the hippocampus during epileptiform activity. Maximal decreases in [Ca 2+ ] o in CA1 were measured in the pyramidal cell layer during 20 Hz, 20 sec stimulus trains to the contralateral CA3 region. Maximal decreases in [Ca 2+ ] o in the dentate gyrus were measured when maximal dentate activation had appeared -irrespective of the location, frequency or duration of the stimulation. Maximal decreases were 36% greater in the dentate gyrus than in CA1. During prolonged discharges, [Ca 2+ ] o recovered partially towards the baseline in both hippocampal regions. To investigate the role of astrocytes, local injections of fluorocitrate (FC), a metabolic toxin selectively taken up by astrocytes, were used. FC (0.1, 0.25 or 0.5 mM FC), but not vehicle (2 l), caused a small, but significant decrease in the maximal changes in CA1, but an increase in the dentate gyrus. The results suggest that maximal decreases in [Ca 2+ ] o occur in the hippocampus in response to burst firing of neurons and that astrocytes play a minimal role in the regulation of [Ca 2+ ] o during epileptiform activity.

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Segregated Expression of AMPA-Type Glutamate Receptors and Glutamate Transporters Defines Distinct Astrocyte Populations in the Mouse Hippocampus

Cited by 403 publications

References 53 publications

NAD(P)H Fluorescence Transients after Synaptic Activity in Brain Slices: Predominant Role of Mitochondrial Function

NAD(P)H Fluorescence Transients after Synaptic Activity in Brain Slices: Predominant Role of Mitochondrial Function

Functions of optic nerve glia: axoglial signalling in physiology and pathology

Regulation of extracellular calcium in the hippocampus in vivo during epileptiform activity—Role of astrocytes

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