Research article

Rhythm generation by the pre-Bötzinger Complex in medullary slice and island preparations: Effects of adenosine A₁ receptor activation

Richard J VanDam^* , Edward J Shields^* and Jonathan D Kelty

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

author email corresponding author email* Contributed equally

BMC Neuroscience 2008, 9:95doi:10.1186/1471-2202-9-95

Published:	1 October 2008

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 A₁ receptors (A₁R) depresses preBötC rhythmogenesis. Although it remains unclear whether A₁R activation is important for organisms in a normal metabolic state, A₁R activation is important to the response of the preBötC to metabolic stress, such as hypoxia. This study examined mechanisms linking A₁R 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 A₁R 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_Aergic or GABA_Aergic and glycinergic transmission were blocked, and in islands when GABA_Aergic 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 A₁R activation involves both decreased neuronal excitability and diminished inter-neuronal communication.