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Volume 2 Supplement 1

Neural Control of Breathing

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The neural mechanisms involved in the generation of three types of respiratory activities in the transverse slice preparation of mice

The transverse medullary slice preparation of mice expresses three distinct types of fictive respiratory activity patterns, that are generated within the pre-Bötzinger complex [1]. Under normoxic conditions these patterns include both fictive eupneic and sigh activity. Sighs occur at a lower frequency than eupnea. Respiratory neurons in the pre-Bötzinger complex that are active during eupneic activity also burst during the sigh. The sigh burst was selectively blocked by DL-AP5 (50 μM) and low concentrations of cadmium (4 μM). In contrast, the generation of eupneic bursts was not abolished at these concentrations. Thus, although there is an overlap between the neural populations underlying the generation of both activities our data suggest that different burst generating mechanisms underlie eupneic and sigh bursts.

During prolonged hypoxic conditions sigh and eupneic activity cease and the respiratory network continues to generate a rhythmic activity, which we refer to as fictive gasping. The duration and rise time of integrated inspiratory activity decreases significantly during the transition from fictive eupnea to gasping. Further, phasic synaptic inhibition in expiratory neurons is suppressed and post-inspiratory neurons are transiently activated in phase with inspiratory activity. We postulate that the same neuronal network in the pre-Bötzinger complex generates both eupneic and gasping activity via a network reconfiguration that involves a selective suppression of synaptic inhibition. This suppression leads to changes in the shape of inspiratory activity, a suppression of phasic hyperpolarization in expiratory neurons, and an inspiratory activation of post-inspiratory neurons.

In the presentation, we will discuss the interaction of pacemaker and network properties in the generation of the frequency, shape, and amplitude of the different respiratory activities. We will present evidence indicating that non-NMDA, NMDA, glycinergic, GABAer-gic and electric synaptic mechanisms are all essential for the generation of fictive eupneic activity. In contrast, synaptic inhibitory mechanisms appear not to be essential for the generation of gasping activity.


  1. Lieske SP, Thoby-Brisson M, Telgkamp P, Ramirez JM: Reconfiguration of the neural network controlling multiple breathing patterns: eupnea, sighs and gasps. Nat Neurosci. 2000, 3: 600-607. 10.1038/75776.

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This study was approved by the University of Chicago Animal Care Committee. Supported by the National Institute of Health.

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Nagel, I., Lieske SP, S., Thoby-Brisson, M. et al. The neural mechanisms involved in the generation of three types of respiratory activities in the transverse slice preparation of mice. Respir Res 2 (Suppl 1), 2.7 (2001).

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