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β-Noradrenergic receptor activation specifically modulates the generation of sighs in vivo and in vitro.

Viemari JC, Garcia AJ, Doi A, Elsen G, Ramirez JM - Front Neural Circuits (2013)

Bottom Line: By contrast, all parameters of bursting pacemakers that rely on the non-specific cation current (I(CAN)) remained unaffected.Moreover, riluzole, which blocks bursting in I(Nap) pacemakers abolished sighs altogether, while flufenamic acid (FFA) which blocks the I(CAN) current did not alter the sigh-increasing effect caused by β-NR.Our results suggest that the selective β-NR action of sighs may result from the modulation of I(Nap) pacemaker activity and that disturbances in noradrenergic system may contribute to abnormal arousal response.

View Article: PubMed Central - PubMed

Affiliation: Team P3M, Institut de Neurosciences de la Timone, UMR 7289, CNRS, Aix Marseille Univesité , Marseille, France.

ABSTRACT
The pre-Bötzinger complex (preBötC), an area that is critical for generating breathing (eupnea), gasps and sighs is continuously modulated by catecholamines. These amines and the generation of sighs have also been implicated in the regulation of arousal. Here we studied the catecholaminergic modulation of sighs not only in anesthetized freely breathing mice (in vivo), but also in medullary slice preparations that contain the preBötC and that generate fictive eupneic and sigh rhythms in vitro. We demonstrate that activating β-noradrenergic receptors (β-NR) specifically increases the frequency of sighs, while eupnea remains unaffected both in vitro and in vivo. β-NR activation specifically increased the frequency of intrinsically bursting pacemaker neurons that rely on persistent sodium current (I(Nap)). By contrast, all parameters of bursting pacemakers that rely on the non-specific cation current (I(CAN)) remained unaffected. Moreover, riluzole, which blocks bursting in I(Nap) pacemakers abolished sighs altogether, while flufenamic acid (FFA) which blocks the I(CAN) current did not alter the sigh-increasing effect caused by β-NR. Our results suggest that the selective β-NR action of sighs may result from the modulation of I(Nap) pacemaker activity and that disturbances in noradrenergic system may contribute to abnormal arousal response. The β-NR action on the preBötC may be an important mechanism in modulating behaviors that are specifically associated with sighs, such as the regulation of the early events leading to the arousal response.

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β-NR modulation does not alter the strength of evoked EPSP in preBötC neurons. Top: Representative traces of an electrically evoked EPSP from an preBötC neuron prior to (Control) and during application of isoproterenol (Isoproterenol). Bottom: Summary of the effect of isoproterenol (20–25 mM) on the amplitude of the evoked EPSP (N.S. P > 0.05; n = 5).
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Figure 5: β-NR modulation does not alter the strength of evoked EPSP in preBötC neurons. Top: Representative traces of an electrically evoked EPSP from an preBötC neuron prior to (Control) and during application of isoproterenol (Isoproterenol). Bottom: Summary of the effect of isoproterenol (20–25 mM) on the amplitude of the evoked EPSP (N.S. P > 0.05; n = 5).

Mentions: In an attempt to unravel the cellular mechanisms that underlie the action of β-NR, we investigated the effects of isoproterenol on evoked excitatory synaptic transmission between inspiratory neurons using methodology as previously used by Lieske and Ramirez (2006a). Neurons activated by the contralateral stimulation correspond to monosynaptically connected, glutamatergic preBötC neurons (Bouvier et al., 2010). Isoproterenol had no significant effects on the evoked EPSPs within the preBötC (Figure 5; n = 5). Although, these experiments cannot exclude the possibility that other, unexplored, connections were affected by isoproterenol, our data suggest that the principal effect of β-NR is not mediated by a general change in excitatory synaptic transmission.


β-Noradrenergic receptor activation specifically modulates the generation of sighs in vivo and in vitro.

Viemari JC, Garcia AJ, Doi A, Elsen G, Ramirez JM - Front Neural Circuits (2013)

β-NR modulation does not alter the strength of evoked EPSP in preBötC neurons. Top: Representative traces of an electrically evoked EPSP from an preBötC neuron prior to (Control) and during application of isoproterenol (Isoproterenol). Bottom: Summary of the effect of isoproterenol (20–25 mM) on the amplitude of the evoked EPSP (N.S. P > 0.05; n = 5).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824105&req=5

Figure 5: β-NR modulation does not alter the strength of evoked EPSP in preBötC neurons. Top: Representative traces of an electrically evoked EPSP from an preBötC neuron prior to (Control) and during application of isoproterenol (Isoproterenol). Bottom: Summary of the effect of isoproterenol (20–25 mM) on the amplitude of the evoked EPSP (N.S. P > 0.05; n = 5).
Mentions: In an attempt to unravel the cellular mechanisms that underlie the action of β-NR, we investigated the effects of isoproterenol on evoked excitatory synaptic transmission between inspiratory neurons using methodology as previously used by Lieske and Ramirez (2006a). Neurons activated by the contralateral stimulation correspond to monosynaptically connected, glutamatergic preBötC neurons (Bouvier et al., 2010). Isoproterenol had no significant effects on the evoked EPSPs within the preBötC (Figure 5; n = 5). Although, these experiments cannot exclude the possibility that other, unexplored, connections were affected by isoproterenol, our data suggest that the principal effect of β-NR is not mediated by a general change in excitatory synaptic transmission.

Bottom Line: By contrast, all parameters of bursting pacemakers that rely on the non-specific cation current (I(CAN)) remained unaffected.Moreover, riluzole, which blocks bursting in I(Nap) pacemakers abolished sighs altogether, while flufenamic acid (FFA) which blocks the I(CAN) current did not alter the sigh-increasing effect caused by β-NR.Our results suggest that the selective β-NR action of sighs may result from the modulation of I(Nap) pacemaker activity and that disturbances in noradrenergic system may contribute to abnormal arousal response.

View Article: PubMed Central - PubMed

Affiliation: Team P3M, Institut de Neurosciences de la Timone, UMR 7289, CNRS, Aix Marseille Univesité , Marseille, France.

ABSTRACT
The pre-Bötzinger complex (preBötC), an area that is critical for generating breathing (eupnea), gasps and sighs is continuously modulated by catecholamines. These amines and the generation of sighs have also been implicated in the regulation of arousal. Here we studied the catecholaminergic modulation of sighs not only in anesthetized freely breathing mice (in vivo), but also in medullary slice preparations that contain the preBötC and that generate fictive eupneic and sigh rhythms in vitro. We demonstrate that activating β-noradrenergic receptors (β-NR) specifically increases the frequency of sighs, while eupnea remains unaffected both in vitro and in vivo. β-NR activation specifically increased the frequency of intrinsically bursting pacemaker neurons that rely on persistent sodium current (I(Nap)). By contrast, all parameters of bursting pacemakers that rely on the non-specific cation current (I(CAN)) remained unaffected. Moreover, riluzole, which blocks bursting in I(Nap) pacemakers abolished sighs altogether, while flufenamic acid (FFA) which blocks the I(CAN) current did not alter the sigh-increasing effect caused by β-NR. Our results suggest that the selective β-NR action of sighs may result from the modulation of I(Nap) pacemaker activity and that disturbances in noradrenergic system may contribute to abnormal arousal response. The β-NR action on the preBötC may be an important mechanism in modulating behaviors that are specifically associated with sighs, such as the regulation of the early events leading to the arousal response.

Show MeSH
Related in: MedlinePlus