Generation of Eupnea and Sighs by a Spatiochemically Organized Inspiratory Network

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Abstract
The discovery of the rhythmogenic pre-Bötzinger complex (preBötC) inspiratory network, which remains active in a transverse brainstem slice, greatly increased the understanding of neural respiratory control. However, basic questions remain unanswered such as (1) What are the necessary and sufficient slice boundaries for a functional preBötC? (2) Is the minimal preBötC capable of reconfiguring between inspiratory-related patterns (e.g., fictive eupnea and sighs)? (3) How is preBötC activity affected by surrounding structures? Using newborn rat slices with systematically varied dimensions in physiological [K+] (3 mm), we found that a 175 μm thickness is sufficient for generating inspiratory-related rhythms. In 700-μm-thick slices with unilaterally exposed preBötC, a kernel 2+imaging revealed that preBötC neurons reconfigure between eupnea and eupnea–sigh burst patterns. We hypothesize a (gradient-like) spatiochemical organization of regions adjacent to the preBötC, such that a small preBötC inspiratory-related oscillator generates eupnea under the dominant influence of caudal structures or thyrotropin-releasing hormone-like transmitters but eupnea–sigh activity when the influence of rostral structures or substance-P-like transmitters predominates.

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