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Neuronal and astroglial correlates underlying spatiotemporal intrinsic optical signal in the rat hippocampal slice.

Pál I, Nyitrai G, Kardos J, Héja L - PLoS ONE (2013)

Bottom Line: It was eliminated by tetrodotoxin blockade of voltage-gated Na(+) channels and was significantly enhanced by suppressing inhibitory signaling with gamma-aminobutyric acid(A) receptor antagonist picrotoxin.We found that IOS was predominantly initiated by postsynaptic Glu receptor activation and progressed by the activation of astroglial Glu transporters and Mg(2+)-independent astroglial N-methyl-D-aspartate receptors.Our model may help to better interpret in vivo IOS and support diagnosis in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Functional Pharmacology, Institute of Molecular Pharmacology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary. pal.ildiko@ttk.mta.hu

ABSTRACT
Widely used for mapping afferent activated brain areas in vivo, the label-free intrinsic optical signal (IOS) is mainly ascribed to blood volume changes subsequent to glial glutamate uptake. By contrast, IOS imaged in vitro is generally attributed to neuronal and glial cell swelling, however the relative contribution of different cell types and molecular players remained largely unknown. We characterized IOS to Schaffer collateral stimulation in the rat hippocampal slice using a 464-element photodiode-array device that enables IOS monitoring at 0.6 ms time-resolution in combination with simultaneous field potential recordings. We used brief half-maximal stimuli by applying a medium intensity 50 Volt-stimulus train within 50 ms (20 Hz). IOS was primarily observed in the str. pyramidale and proximal region of the str. radiatum of the hippocampus. It was eliminated by tetrodotoxin blockade of voltage-gated Na(+) channels and was significantly enhanced by suppressing inhibitory signaling with gamma-aminobutyric acid(A) receptor antagonist picrotoxin. We found that IOS was predominantly initiated by postsynaptic Glu receptor activation and progressed by the activation of astroglial Glu transporters and Mg(2+)-independent astroglial N-methyl-D-aspartate receptors. Under control conditions, role for neuronal K(+)/Cl(-) cotransporter KCC2, but not for glial Na(+)/K(+)/Cl(-) cotransporter NKCC1 was observed. Slight enhancement and inhibition of IOS through non-specific Cl(-) and volume-regulated anion channels, respectively, were also depicted. High-frequency IOS imaging, evoked by brief afferent stimulation in brain slices provide a new paradigm for studying mechanisms underlying IOS genesis. Major players disclosed this way imply that spatiotemporal IOS reflects glutamatergic neuronal activation and astroglial response, as observed within the hippocampus. Our model may help to better interpret in vivo IOS and support diagnosis in the future.

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Molecular dissection of processes underlying spatiotemporal IOS generation.Neuronal (left) and glial (right) proteins underlying IOS mechanism are sized in accordance with their contribution to IOS genesis. Neurons are activated first after Schaffer collateral stimulation, followed by neuronal somatic swelling and subsequent swelling of glial cells.
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pone-0057694-g007: Molecular dissection of processes underlying spatiotemporal IOS generation.Neuronal (left) and glial (right) proteins underlying IOS mechanism are sized in accordance with their contribution to IOS genesis. Neurons are activated first after Schaffer collateral stimulation, followed by neuronal somatic swelling and subsequent swelling of glial cells.

Mentions: Major findings obtained by this paradigm are summarized as follows: i) IOS appears first in the str. pyramidale, indicating that neuronal activation precedes IOS signal generation, ii) lack of action potentials via blockade of voltage-gated Na+ channels abolishes IOS generation, iii) inhibition of GABAA receptor mediated inhibitory signaling substantially increases IOS, iv) IOS evolves through activation of ionotropic Glu receptors, v) astrocytes also participate in IOS generation by means of astroglial EAAT2 and Mg2+-independent NMDA receptor activation, vi) activity of neuronal K+/Cl− but not the glial Na+/K+/Cl− cotransporter contributes to IOS development, connecting neuronal activity to cell swelling, vii) VRAC attenuate, while non-specific Cl− channels intensify IOS when activated. Molecular and cellular dissections of processes underlying spatiotemporal IOS generation in hippocampal slices are illustrated in Figure 7.


Neuronal and astroglial correlates underlying spatiotemporal intrinsic optical signal in the rat hippocampal slice.

Pál I, Nyitrai G, Kardos J, Héja L - PLoS ONE (2013)

Molecular dissection of processes underlying spatiotemporal IOS generation.Neuronal (left) and glial (right) proteins underlying IOS mechanism are sized in accordance with their contribution to IOS genesis. Neurons are activated first after Schaffer collateral stimulation, followed by neuronal somatic swelling and subsequent swelling of glial cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585794&req=5

pone-0057694-g007: Molecular dissection of processes underlying spatiotemporal IOS generation.Neuronal (left) and glial (right) proteins underlying IOS mechanism are sized in accordance with their contribution to IOS genesis. Neurons are activated first after Schaffer collateral stimulation, followed by neuronal somatic swelling and subsequent swelling of glial cells.
Mentions: Major findings obtained by this paradigm are summarized as follows: i) IOS appears first in the str. pyramidale, indicating that neuronal activation precedes IOS signal generation, ii) lack of action potentials via blockade of voltage-gated Na+ channels abolishes IOS generation, iii) inhibition of GABAA receptor mediated inhibitory signaling substantially increases IOS, iv) IOS evolves through activation of ionotropic Glu receptors, v) astrocytes also participate in IOS generation by means of astroglial EAAT2 and Mg2+-independent NMDA receptor activation, vi) activity of neuronal K+/Cl− but not the glial Na+/K+/Cl− cotransporter contributes to IOS development, connecting neuronal activity to cell swelling, vii) VRAC attenuate, while non-specific Cl− channels intensify IOS when activated. Molecular and cellular dissections of processes underlying spatiotemporal IOS generation in hippocampal slices are illustrated in Figure 7.

Bottom Line: It was eliminated by tetrodotoxin blockade of voltage-gated Na(+) channels and was significantly enhanced by suppressing inhibitory signaling with gamma-aminobutyric acid(A) receptor antagonist picrotoxin.We found that IOS was predominantly initiated by postsynaptic Glu receptor activation and progressed by the activation of astroglial Glu transporters and Mg(2+)-independent astroglial N-methyl-D-aspartate receptors.Our model may help to better interpret in vivo IOS and support diagnosis in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Functional Pharmacology, Institute of Molecular Pharmacology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary. pal.ildiko@ttk.mta.hu

ABSTRACT
Widely used for mapping afferent activated brain areas in vivo, the label-free intrinsic optical signal (IOS) is mainly ascribed to blood volume changes subsequent to glial glutamate uptake. By contrast, IOS imaged in vitro is generally attributed to neuronal and glial cell swelling, however the relative contribution of different cell types and molecular players remained largely unknown. We characterized IOS to Schaffer collateral stimulation in the rat hippocampal slice using a 464-element photodiode-array device that enables IOS monitoring at 0.6 ms time-resolution in combination with simultaneous field potential recordings. We used brief half-maximal stimuli by applying a medium intensity 50 Volt-stimulus train within 50 ms (20 Hz). IOS was primarily observed in the str. pyramidale and proximal region of the str. radiatum of the hippocampus. It was eliminated by tetrodotoxin blockade of voltage-gated Na(+) channels and was significantly enhanced by suppressing inhibitory signaling with gamma-aminobutyric acid(A) receptor antagonist picrotoxin. We found that IOS was predominantly initiated by postsynaptic Glu receptor activation and progressed by the activation of astroglial Glu transporters and Mg(2+)-independent astroglial N-methyl-D-aspartate receptors. Under control conditions, role for neuronal K(+)/Cl(-) cotransporter KCC2, but not for glial Na(+)/K(+)/Cl(-) cotransporter NKCC1 was observed. Slight enhancement and inhibition of IOS through non-specific Cl(-) and volume-regulated anion channels, respectively, were also depicted. High-frequency IOS imaging, evoked by brief afferent stimulation in brain slices provide a new paradigm for studying mechanisms underlying IOS genesis. Major players disclosed this way imply that spatiotemporal IOS reflects glutamatergic neuronal activation and astroglial response, as observed within the hippocampus. Our model may help to better interpret in vivo IOS and support diagnosis in the future.

Show MeSH
Related in: MedlinePlus