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Rhythm generation by the pre-Bötzinger complex in medullary slice and island preparations: effects of adenosine A(1) receptor activation.

Vandam RJ, Shields EJ, Kelty JD - BMC Neurosci (2008)

Bottom Line: The A(1)R agonist N6-Cyclopentyladenosine (NCPA) reduced population burst frequency in slices by ca. 33% and in islands by ca. 30%.Converting slices to island preparations decreased synaptic input to inspiratory neurons.NCPA further decreased the frequency of synaptic inputs to neurons in island preparations and lowered the input resistance of inspiratory neurons, even when chemical communication between neurons and other cells was impeded.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, Central Michigan University, Mount Pleasant, MI 48858, USA.

ABSTRACT

Background: The pre-Bötzinger complex (preBötC) is a central pattern generator within the ventrolateral medulla oblongata's ventral respiratory group that is important for the generation of respiratory rhythm. Activation of adenosine A(1) receptors (A(1)R) depresses preBötC rhythmogenesis. Although it remains unclear whether A(1)R activation is important for organisms in a normal metabolic state, A(1)R activation is important to the response of the preBötC to metabolic stress, such as hypoxia. This study examined mechanisms linking A(1)R activation to depression of preBötC rhythmogenesis in medullary slice and island preparations from neonatal mice.

Results: Converting medullary slices to islands by cutting away much of the medullary tissue adjacent to the preBötC decreased the amplitude of action potential bursts generated by a population of neurons within the preBötC (recorded with an extracellular electrode, and integrated using a hardware integrator), without noticeably affecting burst frequency. The A(1)R agonist N6-Cyclopentyladenosine (NCPA) reduced population burst frequency in slices by ca. 33% and in islands by ca. 30%. As in normal (drug-free) artificial cerebrospinal fluid (aCSF), NCPA decreased burst frequency in slices when GABA(A)ergic or GABA(A)ergic and glycinergic transmission were blocked, and in islands when GABA(A)ergic transmission was antagonized. Converting slices to island preparations decreased synaptic input to inspiratory neurons. NCPA further decreased the frequency of synaptic inputs to neurons in island preparations and lowered the input resistance of inspiratory neurons, even when chemical communication between neurons and other cells was impeded.

Conclusion: Together these data support the suggestion that depression of preBötC activity by A(1)R activation involves both decreased neuronal excitability and diminished inter-neuronal communication.

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Block of chloride-mediated inhibition inducesseizure-like activity in medullary slice preparations. Three sequential sample recordings of integrated preBötC activity from a single medullary slice preparation. A. Activity recorded in recorded in drug free aCSF. B. Gabazine (20 μM) and Strychnine (1 μM) induce seizure-like bursting (brackets) characterized by increased burst frequency and elevated baseline, while slightly decreasing the frequency of population bursts generated between seizure-like bursts. C. Antagonism of A1R with NCPA (1 μM) eliminated seizures for this slice and decreased population burst frequency.
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Figure 2: Block of chloride-mediated inhibition inducesseizure-like activity in medullary slice preparations. Three sequential sample recordings of integrated preBötC activity from a single medullary slice preparation. A. Activity recorded in recorded in drug free aCSF. B. Gabazine (20 μM) and Strychnine (1 μM) induce seizure-like bursting (brackets) characterized by increased burst frequency and elevated baseline, while slightly decreasing the frequency of population bursts generated between seizure-like bursts. C. Antagonism of A1R with NCPA (1 μM) eliminated seizures for this slice and decreased population burst frequency.

Mentions: In all 8 slices examined, a cocktail of gabazine (20 μM) and strychnine (1 μM) induced seizure-like bursting at 1.36 ± 0.22 siezures·min-1 (Fig. 2. During subsequent agonism of A1R with NCPA seizures occurred at 0.71 ± 0.47 seizures·min-1 (P > 0.05, Tukey Test). Blockade of Cl--mediated transmission did not discernibly affect the overall frequency of population bursting. Even with GABAAergic and glycinergic transmission antagonized, NCPA decreased the frequency of population bursts relative to baseline (Fig. 1A, B; P = 0.002, Tukey Test). This change in frequency was indistinguishable from the ~27.2% decrease observed in slices treated with NCPA alone. Although a repeated measures ANOVA indicated significant overall variation in amplitude between all treatments (in slices treated with gabazine and strychnine; P = 0.044), Tukey post-hoc tests demonstrated that none of the individual pairs of treatments were distinguishable from each other (Table 1).


Rhythm generation by the pre-Bötzinger complex in medullary slice and island preparations: effects of adenosine A(1) receptor activation.

Vandam RJ, Shields EJ, Kelty JD - BMC Neurosci (2008)

Block of chloride-mediated inhibition inducesseizure-like activity in medullary slice preparations. Three sequential sample recordings of integrated preBötC activity from a single medullary slice preparation. A. Activity recorded in recorded in drug free aCSF. B. Gabazine (20 μM) and Strychnine (1 μM) induce seizure-like bursting (brackets) characterized by increased burst frequency and elevated baseline, while slightly decreasing the frequency of population bursts generated between seizure-like bursts. C. Antagonism of A1R with NCPA (1 μM) eliminated seizures for this slice and decreased population burst frequency.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2567986&req=5

Figure 2: Block of chloride-mediated inhibition inducesseizure-like activity in medullary slice preparations. Three sequential sample recordings of integrated preBötC activity from a single medullary slice preparation. A. Activity recorded in recorded in drug free aCSF. B. Gabazine (20 μM) and Strychnine (1 μM) induce seizure-like bursting (brackets) characterized by increased burst frequency and elevated baseline, while slightly decreasing the frequency of population bursts generated between seizure-like bursts. C. Antagonism of A1R with NCPA (1 μM) eliminated seizures for this slice and decreased population burst frequency.
Mentions: In all 8 slices examined, a cocktail of gabazine (20 μM) and strychnine (1 μM) induced seizure-like bursting at 1.36 ± 0.22 siezures·min-1 (Fig. 2. During subsequent agonism of A1R with NCPA seizures occurred at 0.71 ± 0.47 seizures·min-1 (P > 0.05, Tukey Test). Blockade of Cl--mediated transmission did not discernibly affect the overall frequency of population bursting. Even with GABAAergic and glycinergic transmission antagonized, NCPA decreased the frequency of population bursts relative to baseline (Fig. 1A, B; P = 0.002, Tukey Test). This change in frequency was indistinguishable from the ~27.2% decrease observed in slices treated with NCPA alone. Although a repeated measures ANOVA indicated significant overall variation in amplitude between all treatments (in slices treated with gabazine and strychnine; P = 0.044), Tukey post-hoc tests demonstrated that none of the individual pairs of treatments were distinguishable from each other (Table 1).

Bottom Line: The A(1)R agonist N6-Cyclopentyladenosine (NCPA) reduced population burst frequency in slices by ca. 33% and in islands by ca. 30%.Converting slices to island preparations decreased synaptic input to inspiratory neurons.NCPA further decreased the frequency of synaptic inputs to neurons in island preparations and lowered the input resistance of inspiratory neurons, even when chemical communication between neurons and other cells was impeded.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, Central Michigan University, Mount Pleasant, MI 48858, USA.

ABSTRACT

Background: The pre-Bötzinger complex (preBötC) is a central pattern generator within the ventrolateral medulla oblongata's ventral respiratory group that is important for the generation of respiratory rhythm. Activation of adenosine A(1) receptors (A(1)R) depresses preBötC rhythmogenesis. Although it remains unclear whether A(1)R activation is important for organisms in a normal metabolic state, A(1)R activation is important to the response of the preBötC to metabolic stress, such as hypoxia. This study examined mechanisms linking A(1)R activation to depression of preBötC rhythmogenesis in medullary slice and island preparations from neonatal mice.

Results: Converting medullary slices to islands by cutting away much of the medullary tissue adjacent to the preBötC decreased the amplitude of action potential bursts generated by a population of neurons within the preBötC (recorded with an extracellular electrode, and integrated using a hardware integrator), without noticeably affecting burst frequency. The A(1)R agonist N6-Cyclopentyladenosine (NCPA) reduced population burst frequency in slices by ca. 33% and in islands by ca. 30%. As in normal (drug-free) artificial cerebrospinal fluid (aCSF), NCPA decreased burst frequency in slices when GABA(A)ergic or GABA(A)ergic and glycinergic transmission were blocked, and in islands when GABA(A)ergic transmission was antagonized. Converting slices to island preparations decreased synaptic input to inspiratory neurons. NCPA further decreased the frequency of synaptic inputs to neurons in island preparations and lowered the input resistance of inspiratory neurons, even when chemical communication between neurons and other cells was impeded.

Conclusion: Together these data support the suggestion that depression of preBötC activity by A(1)R activation involves both decreased neuronal excitability and diminished inter-neuronal communication.

Show MeSH
Related in: MedlinePlus