Vandam Richard J, Shields Edward J, Kelty Jonathan D
Department of Biology, Central Michigan University, Mount Pleasant, MI 48858, USA.
BMC Neurosci. 2008 Oct 1;9:95. doi: 10.1186/1471-2202-9-95.
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.
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.
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.
前包钦格复合体（preBötC）是延髓腹外侧呼吸组内的一个中枢模式发生器，对呼吸节律的产生至关重要。腺苷A(1)受体（A(1)R）的激活会抑制preBötC的节律发生。虽然尚不清楚A(1)R激活在正常代谢状态下对生物体是否重要，但A(1)R激活对preBötC对代谢应激（如缺氧）的反应很重要。本研究探讨了在新生小鼠的延髓切片和脑岛标本中，将A(1)R激活与preBötC节律发生抑制联系起来的机制。
通过切除preBötC附近的大部分延髓组织将延髓切片转化为脑岛，可降低preBötC内一群神经元产生的动作电位爆发的幅度（用细胞外电极记录，并用硬件积分器积分），而对爆发频率没有明显影响。A(1)R激动剂N6-环戊基腺苷（NCPA）使切片中的群体爆发频率降低约33%，使脑岛中的群体爆发频率降低约30%。与在正常（无药物）人工脑脊液（aCSF）中一样，当GABA(A)能或GABA(A)能和甘氨酸能传递被阻断时，NCPA降低了切片中的爆发频率；当GABA(A)能传递被拮抗时，NCPA降低了脑岛中的爆发频率。将切片转化为脑岛标本可减少吸气神经元的突触输入。即使在神经元与其他细胞之间的化学通讯受到阻碍时，NCPA也会进一步降低脑岛标本中神经元的突触输入频率，并降低吸气神经元的输入电阻。
这些数据共同支持这样的观点，即A(1)R激活导致的preBötC活性抑制涉及神经元兴奋性降低和神经元间通讯减少。
