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ATP-dependent infra-slow (<0.1 Hz) oscillations in thalamic networks.

Lörincz ML, Geall F, Bao Y, Crunelli V, Hughes SW - PLoS ONE (2009)

Bottom Line: This ISO is a neuronal population phenomenon which modulates faster gap junction (GJ)-dependent network oscillations, and can underlie epileptic activity when AchRs or mGluRs are stimulated excessively.In individual thalamocortical neurons the ISO is primarily shaped by rhythmic, long-lasting hyperpolarizing potentials which reflect the activation of A1 receptors, by ATP-derived adenosine, and subsequent opening of Ba(2+)-sensitive K(+) channels.We argue that this ISO has a likely non-neuronal origin and may contribute to shaping ISOs in the intact brain.

View Article: PubMed Central - PubMed

Affiliation: School of Biosciences, Cardiff University, Cardiff, UK.

ABSTRACT
An increasing number of EEG and resting state fMRI studies in both humans and animals indicate that spontaneous low frequency fluctuations in cerebral activity at <0.1 Hz (infra-slow oscillations, ISOs) represent a fundamental component of brain functioning, being known to correlate with faster neuronal ensemble oscillations, regulate behavioural performance and influence seizure susceptibility. Although these oscillations have been commonly indicated to involve the thalamus their basic cellular mechanisms remain poorly understood. Here we show that various nuclei in the dorsal thalamus in vitro can express a robust ISO at approximately 0.005-0.1 Hz that is greatly facilitated by activating metabotropic glutamate receptors (mGluRs) and/or Ach receptors (AchRs). This ISO is a neuronal population phenomenon which modulates faster gap junction (GJ)-dependent network oscillations, and can underlie epileptic activity when AchRs or mGluRs are stimulated excessively. In individual thalamocortical neurons the ISO is primarily shaped by rhythmic, long-lasting hyperpolarizing potentials which reflect the activation of A1 receptors, by ATP-derived adenosine, and subsequent opening of Ba(2+)-sensitive K(+) channels. We argue that this ISO has a likely non-neuronal origin and may contribute to shaping ISOs in the intact brain.

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The long-lasting rhythmic hyperpolarizing potentials reflect activation of A1 receptors by ATP-derived adenosine.A. Complete block of the ISO in an LGN TC neuron following application of the A1 receptor antagonist DPCPX (5 µM). B. Top panel: simultaneous LFP and intracellular TC neuron recording of the ISO in the LGN. Below: DPCPX disrupts the expression of the ISO in the intracellular recording but not in the LFP. This is more clearly illustrated by the membrane potential averages shown below which reveal that the long-lasting hyperpolarizing potentials observed prior to DPCPX application (left) are abolished and replaced by a shorter lasting (∼1 s) depolarizing event (right). C. Plots showing the effect of DPCPX on the mean duration of the silent period (top) and the overall frequency (bottom) of an ISO observed with an extracellular single unit recording in the VB in the presence of 50 µM Cch. D. Extracellular single unit recording of a VB TC neuron exhibiting the ISO in the presence of 50 µM Cch. The ecto-ATPase inhibitor ARL67156 reversibly converts the ISO into continuous firing. (action potentials have been truncated in A and B).
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pone-0004447-g007: The long-lasting rhythmic hyperpolarizing potentials reflect activation of A1 receptors by ATP-derived adenosine.A. Complete block of the ISO in an LGN TC neuron following application of the A1 receptor antagonist DPCPX (5 µM). B. Top panel: simultaneous LFP and intracellular TC neuron recording of the ISO in the LGN. Below: DPCPX disrupts the expression of the ISO in the intracellular recording but not in the LFP. This is more clearly illustrated by the membrane potential averages shown below which reveal that the long-lasting hyperpolarizing potentials observed prior to DPCPX application (left) are abolished and replaced by a shorter lasting (∼1 s) depolarizing event (right). C. Plots showing the effect of DPCPX on the mean duration of the silent period (top) and the overall frequency (bottom) of an ISO observed with an extracellular single unit recording in the VB in the presence of 50 µM Cch. D. Extracellular single unit recording of a VB TC neuron exhibiting the ISO in the presence of 50 µM Cch. The ecto-ATPase inhibitor ARL67156 reversibly converts the ISO into continuous firing. (action potentials have been truncated in A and B).

Mentions: At the concentration used (i.e. 100 µM), Ba2+ preferentially blocks G protein-coupled inwardly rectifying K+ (GIRK) channels [32] suggesting that long-lasting hyperpolarizing potentials might be due to the opening of these channels via the phasic activation of receptors on TC neurons to which they are positively coupled. Apart from GABAB receptors [33], the other main receptor type that is known to be positively coupled to GIRK channels in TC neurons is the adenosine A1 receptor [34]. We therefore tested the effect of the A1 receptor antagonist, DPCPX (2–5 µM) on the generation of ISO-related long-lasting hyperpolarizing potentials. DPCPX abolished these potentials in all cells tested (n = 5) (Fig. 7A and B). Furthermore, and consistent with the effects of Ba2+, this facilitated the expression of depolarizing events (Fig. 7B). Interestingly, DPCPX did not however, affect the generation of the ISO in the LFP (n = 5) (Fig. 7B). In agreement with its effect in intracellular recordings, in all cases, DPCPX (2–5 µM) caused a significant shortening of the quiescent period of the ISO, as observed with single unit extracellular recordings (% of control 22.3±5.0; n = 5), without altering its overall frequency (n = 5) (Fig. 7C).


ATP-dependent infra-slow (<0.1 Hz) oscillations in thalamic networks.

Lörincz ML, Geall F, Bao Y, Crunelli V, Hughes SW - PLoS ONE (2009)

The long-lasting rhythmic hyperpolarizing potentials reflect activation of A1 receptors by ATP-derived adenosine.A. Complete block of the ISO in an LGN TC neuron following application of the A1 receptor antagonist DPCPX (5 µM). B. Top panel: simultaneous LFP and intracellular TC neuron recording of the ISO in the LGN. Below: DPCPX disrupts the expression of the ISO in the intracellular recording but not in the LFP. This is more clearly illustrated by the membrane potential averages shown below which reveal that the long-lasting hyperpolarizing potentials observed prior to DPCPX application (left) are abolished and replaced by a shorter lasting (∼1 s) depolarizing event (right). C. Plots showing the effect of DPCPX on the mean duration of the silent period (top) and the overall frequency (bottom) of an ISO observed with an extracellular single unit recording in the VB in the presence of 50 µM Cch. D. Extracellular single unit recording of a VB TC neuron exhibiting the ISO in the presence of 50 µM Cch. The ecto-ATPase inhibitor ARL67156 reversibly converts the ISO into continuous firing. (action potentials have been truncated in A and B).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2637539&req=5

pone-0004447-g007: The long-lasting rhythmic hyperpolarizing potentials reflect activation of A1 receptors by ATP-derived adenosine.A. Complete block of the ISO in an LGN TC neuron following application of the A1 receptor antagonist DPCPX (5 µM). B. Top panel: simultaneous LFP and intracellular TC neuron recording of the ISO in the LGN. Below: DPCPX disrupts the expression of the ISO in the intracellular recording but not in the LFP. This is more clearly illustrated by the membrane potential averages shown below which reveal that the long-lasting hyperpolarizing potentials observed prior to DPCPX application (left) are abolished and replaced by a shorter lasting (∼1 s) depolarizing event (right). C. Plots showing the effect of DPCPX on the mean duration of the silent period (top) and the overall frequency (bottom) of an ISO observed with an extracellular single unit recording in the VB in the presence of 50 µM Cch. D. Extracellular single unit recording of a VB TC neuron exhibiting the ISO in the presence of 50 µM Cch. The ecto-ATPase inhibitor ARL67156 reversibly converts the ISO into continuous firing. (action potentials have been truncated in A and B).
Mentions: At the concentration used (i.e. 100 µM), Ba2+ preferentially blocks G protein-coupled inwardly rectifying K+ (GIRK) channels [32] suggesting that long-lasting hyperpolarizing potentials might be due to the opening of these channels via the phasic activation of receptors on TC neurons to which they are positively coupled. Apart from GABAB receptors [33], the other main receptor type that is known to be positively coupled to GIRK channels in TC neurons is the adenosine A1 receptor [34]. We therefore tested the effect of the A1 receptor antagonist, DPCPX (2–5 µM) on the generation of ISO-related long-lasting hyperpolarizing potentials. DPCPX abolished these potentials in all cells tested (n = 5) (Fig. 7A and B). Furthermore, and consistent with the effects of Ba2+, this facilitated the expression of depolarizing events (Fig. 7B). Interestingly, DPCPX did not however, affect the generation of the ISO in the LFP (n = 5) (Fig. 7B). In agreement with its effect in intracellular recordings, in all cases, DPCPX (2–5 µM) caused a significant shortening of the quiescent period of the ISO, as observed with single unit extracellular recordings (% of control 22.3±5.0; n = 5), without altering its overall frequency (n = 5) (Fig. 7C).

Bottom Line: This ISO is a neuronal population phenomenon which modulates faster gap junction (GJ)-dependent network oscillations, and can underlie epileptic activity when AchRs or mGluRs are stimulated excessively.In individual thalamocortical neurons the ISO is primarily shaped by rhythmic, long-lasting hyperpolarizing potentials which reflect the activation of A1 receptors, by ATP-derived adenosine, and subsequent opening of Ba(2+)-sensitive K(+) channels.We argue that this ISO has a likely non-neuronal origin and may contribute to shaping ISOs in the intact brain.

View Article: PubMed Central - PubMed

Affiliation: School of Biosciences, Cardiff University, Cardiff, UK.

ABSTRACT
An increasing number of EEG and resting state fMRI studies in both humans and animals indicate that spontaneous low frequency fluctuations in cerebral activity at <0.1 Hz (infra-slow oscillations, ISOs) represent a fundamental component of brain functioning, being known to correlate with faster neuronal ensemble oscillations, regulate behavioural performance and influence seizure susceptibility. Although these oscillations have been commonly indicated to involve the thalamus their basic cellular mechanisms remain poorly understood. Here we show that various nuclei in the dorsal thalamus in vitro can express a robust ISO at approximately 0.005-0.1 Hz that is greatly facilitated by activating metabotropic glutamate receptors (mGluRs) and/or Ach receptors (AchRs). This ISO is a neuronal population phenomenon which modulates faster gap junction (GJ)-dependent network oscillations, and can underlie epileptic activity when AchRs or mGluRs are stimulated excessively. In individual thalamocortical neurons the ISO is primarily shaped by rhythmic, long-lasting hyperpolarizing potentials which reflect the activation of A1 receptors, by ATP-derived adenosine, and subsequent opening of Ba(2+)-sensitive K(+) channels. We argue that this ISO has a likely non-neuronal origin and may contribute to shaping ISOs in the intact brain.

Show MeSH
Related in: MedlinePlus