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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.

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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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Effects of A1R activation on preBötC rhythmogenesis in medullary slice preparations. A. Representative effects of bath-applied NCPA (1 μM) alone, NCPA in the presence of gabazine (20 μM), or NCPA in combination with gabazine (20 μM) and strychnine (1 μM). B. Whether applied (i) alone, (ii) with gabazine, or (iii) with gabazine and strychnine, NCPA decreased burst frequency (a, value different from baseline at P < 0.05, Tukey post-hoc test; b, value different from step 2 of treatment – either continued aCSF, application of gabazine, or application of gabazine and strychnine – at P < 0.05, Tukey post-hoc test).
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Figure 1: Effects of A1R activation on preBötC rhythmogenesis in medullary slice preparations. A. Representative effects of bath-applied NCPA (1 μM) alone, NCPA in the presence of gabazine (20 μM), or NCPA in combination with gabazine (20 μM) and strychnine (1 μM). B. Whether applied (i) alone, (ii) with gabazine, or (iii) with gabazine and strychnine, NCPA decreased burst frequency (a, value different from baseline at P < 0.05, Tukey post-hoc test; b, value different from step 2 of treatment – either continued aCSF, application of gabazine, or application of gabazine and strychnine – at P < 0.05, Tukey post-hoc test).

Mentions: Pharmacological manipulation of A1R affected the generation of population bursts by the preBötC (Repeated Measures ANOVA P < 0.001; Table 1). The A1R agonist NCPA (1 μM) decreased population burst frequency by 27.3% (P < 0.001; Fig. 1A, B. Subsequent addition of the A1R antagonist 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX; 1 μM, n = 12) returned population bursting to essentially baseline frequency (P < 0.001 vs. NCPA; Fig. 1A, B). The amplitude of population bursts generated during NCPA treatment was statistically indistinguishable from that of bursts generated during baseline recording (Repeated Measures ANOVA, P > 0.1; 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)

Effects of A1R activation on preBötC rhythmogenesis in medullary slice preparations. A. Representative effects of bath-applied NCPA (1 μM) alone, NCPA in the presence of gabazine (20 μM), or NCPA in combination with gabazine (20 μM) and strychnine (1 μM). B. Whether applied (i) alone, (ii) with gabazine, or (iii) with gabazine and strychnine, NCPA decreased burst frequency (a, value different from baseline at P < 0.05, Tukey post-hoc test; b, value different from step 2 of treatment – either continued aCSF, application of gabazine, or application of gabazine and strychnine – at P < 0.05, Tukey post-hoc test).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Effects of A1R activation on preBötC rhythmogenesis in medullary slice preparations. A. Representative effects of bath-applied NCPA (1 μM) alone, NCPA in the presence of gabazine (20 μM), or NCPA in combination with gabazine (20 μM) and strychnine (1 μM). B. Whether applied (i) alone, (ii) with gabazine, or (iii) with gabazine and strychnine, NCPA decreased burst frequency (a, value different from baseline at P < 0.05, Tukey post-hoc test; b, value different from step 2 of treatment – either continued aCSF, application of gabazine, or application of gabazine and strychnine – at P < 0.05, Tukey post-hoc test).
Mentions: Pharmacological manipulation of A1R affected the generation of population bursts by the preBötC (Repeated Measures ANOVA P < 0.001; Table 1). The A1R agonist NCPA (1 μM) decreased population burst frequency by 27.3% (P < 0.001; Fig. 1A, B. Subsequent addition of the A1R antagonist 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX; 1 μM, n = 12) returned population bursting to essentially baseline frequency (P < 0.001 vs. NCPA; Fig. 1A, B). The amplitude of population bursts generated during NCPA treatment was statistically indistinguishable from that of bursts generated during baseline recording (Repeated Measures ANOVA, P > 0.1; 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