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TTX-resistant NMDA receptor-mediated membrane potential oscillations in neonatal mouse Hb9 interneurons.

Masino MA, Abbinanti MD, Eian J, Harris-Warrick RM - PLoS ONE (2012)

Bottom Line: Hb9 interneurons are rhythmically active during fictive locomotor-like behavior.In contrast, exogenous serotonin and dopamine application, alone or in combination, are not sufficient.NMDA does not modulate the T-type calcium current (I(Ca(T))), which is thought to be important in generating locomotor-like activity, in Hb9 neurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States of America. masino@umn.edu

ABSTRACT
Conditional neuronal membrane potential oscillations have been identified as a potential mechanism to help support or generate rhythmogenesis in neural circuits. A genetically identified population of ventromedial interneurons, called Hb9, in the mouse spinal cord has been shown to generate TTX-resistant membrane potential oscillations in the presence of NMDA, serotonin and dopamine, but these oscillatory properties are not well characterized. Hb9 interneurons are rhythmically active during fictive locomotor-like behavior. In this study, we report that exogenous N-Methyl-D-Aspartic acid (NMDA) application is sufficient to produce membrane potential oscillations in Hb9 interneurons. In contrast, exogenous serotonin and dopamine application, alone or in combination, are not sufficient. The properties of NMDA-induced oscillations vary among the Hb9 interneuron population; their frequency and amplitude increase with increasing NMDA concentration. NMDA does not modulate the T-type calcium current (I(Ca(T))), which is thought to be important in generating locomotor-like activity, in Hb9 neurons. These results suggest that NMDA receptor activation is sufficient for the generation of TTX-resistant NMDA-induced membrane potential oscillations in Hb9 interneurons.

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NMDA does not potentiate low-threshold calcium current in Hb9 interneurons. A,From top to bottom, current traces elicited by steps from −90 mV to −30 mV in control, 21 μM NMDA, and washout. Note the lack of effect on the current by NMDA. B, Time course of calcium current elicited by steps from −90 to −30 mV versus time. Time course chart and representative sweeps at top are from same experiment. C, Mean peak current amplitudes elicited by steps from −90 to −30 mV in control, 21 μM NMDA, and washout.
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pone-0047940-g005: NMDA does not potentiate low-threshold calcium current in Hb9 interneurons. A,From top to bottom, current traces elicited by steps from −90 mV to −30 mV in control, 21 μM NMDA, and washout. Note the lack of effect on the current by NMDA. B, Time course of calcium current elicited by steps from −90 to −30 mV versus time. Time course chart and representative sweeps at top are from same experiment. C, Mean peak current amplitudes elicited by steps from −90 to −30 mV in control, 21 μM NMDA, and washout.

Mentions: The low-threshold calcium current (ICa(T)) plays a role in chemically-induced locomotor rhythmogenesis and in the generation of membrane potential oscillations in Hb9 interneurons [35], [49]. Thus, we asked whether NMDA could directly potentiate ICa(T) in Hb9 interneurons. We measured a mixture of low- and higher-threshold calcium current before, during, and after the application of 21 µM NMDA. In a series of whole-cell voltage-clamp experiments (n = 10), sodium and potassium channels were blocked and inward calcium current was measured using steps from −90 to −30 mV (4 of 10 preparations expressed ICa(T); Fig. 5A). NMDA (21 µM) did not increase the amplitude of the inward calcium current (F2,9 = 0.20, p = 0.83, n = 4) across a 15-minute recording window (Fig. 5B,C). This suggests that, although ICa(T) is required for NMDA-induced membrane potential oscillations [35], [49], it is not a target of NMDA modulation in Hb9 interneurons.


TTX-resistant NMDA receptor-mediated membrane potential oscillations in neonatal mouse Hb9 interneurons.

Masino MA, Abbinanti MD, Eian J, Harris-Warrick RM - PLoS ONE (2012)

NMDA does not potentiate low-threshold calcium current in Hb9 interneurons. A,From top to bottom, current traces elicited by steps from −90 mV to −30 mV in control, 21 μM NMDA, and washout. Note the lack of effect on the current by NMDA. B, Time course of calcium current elicited by steps from −90 to −30 mV versus time. Time course chart and representative sweeps at top are from same experiment. C, Mean peak current amplitudes elicited by steps from −90 to −30 mV in control, 21 μM NMDA, and washout.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475713&req=5

pone-0047940-g005: NMDA does not potentiate low-threshold calcium current in Hb9 interneurons. A,From top to bottom, current traces elicited by steps from −90 mV to −30 mV in control, 21 μM NMDA, and washout. Note the lack of effect on the current by NMDA. B, Time course of calcium current elicited by steps from −90 to −30 mV versus time. Time course chart and representative sweeps at top are from same experiment. C, Mean peak current amplitudes elicited by steps from −90 to −30 mV in control, 21 μM NMDA, and washout.
Mentions: The low-threshold calcium current (ICa(T)) plays a role in chemically-induced locomotor rhythmogenesis and in the generation of membrane potential oscillations in Hb9 interneurons [35], [49]. Thus, we asked whether NMDA could directly potentiate ICa(T) in Hb9 interneurons. We measured a mixture of low- and higher-threshold calcium current before, during, and after the application of 21 µM NMDA. In a series of whole-cell voltage-clamp experiments (n = 10), sodium and potassium channels were blocked and inward calcium current was measured using steps from −90 to −30 mV (4 of 10 preparations expressed ICa(T); Fig. 5A). NMDA (21 µM) did not increase the amplitude of the inward calcium current (F2,9 = 0.20, p = 0.83, n = 4) across a 15-minute recording window (Fig. 5B,C). This suggests that, although ICa(T) is required for NMDA-induced membrane potential oscillations [35], [49], it is not a target of NMDA modulation in Hb9 interneurons.

Bottom Line: Hb9 interneurons are rhythmically active during fictive locomotor-like behavior.In contrast, exogenous serotonin and dopamine application, alone or in combination, are not sufficient.NMDA does not modulate the T-type calcium current (I(Ca(T))), which is thought to be important in generating locomotor-like activity, in Hb9 neurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States of America. masino@umn.edu

ABSTRACT
Conditional neuronal membrane potential oscillations have been identified as a potential mechanism to help support or generate rhythmogenesis in neural circuits. A genetically identified population of ventromedial interneurons, called Hb9, in the mouse spinal cord has been shown to generate TTX-resistant membrane potential oscillations in the presence of NMDA, serotonin and dopamine, but these oscillatory properties are not well characterized. Hb9 interneurons are rhythmically active during fictive locomotor-like behavior. In this study, we report that exogenous N-Methyl-D-Aspartic acid (NMDA) application is sufficient to produce membrane potential oscillations in Hb9 interneurons. In contrast, exogenous serotonin and dopamine application, alone or in combination, are not sufficient. The properties of NMDA-induced oscillations vary among the Hb9 interneuron population; their frequency and amplitude increase with increasing NMDA concentration. NMDA does not modulate the T-type calcium current (I(Ca(T))), which is thought to be important in generating locomotor-like activity, in Hb9 neurons. These results suggest that NMDA receptor activation is sufficient for the generation of TTX-resistant NMDA-induced membrane potential oscillations in Hb9 interneurons.

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