SELECTIVE LESIONING OF THE CAT PRE-BOTZINGER COMPLEX IN-VIVO ELIMINATES BREATHING BUT NOT GASPING

1. To examine the functional importance of the pre-Botzinger complex f or breathing we microinjected, under in vivo conditions, the calcium c hannel blocker omega-conotoxin GVIA and the sodium channel blocker tet rodotoxin (TTX) into the ventrolateral medulla of adult cats, while mo nitoring respiratory rhythmic motor output in the phrenic nerve. 2. om ega-Conotoxin GVIA caused a highly localized synaptic ablation by bloc king presynaptic N-type calcium channels. When injecting 5-60 fmol ome ga-conotoxin GVIA unilaterally, the amplitude of phrenic nerve activit y decreased bilaterally and sometimes disappeared, indicating central apnoea. These effects were reversible and could only be induced in a v ery localized area of the pre-Botzinger complex. By injecting omega-co notoxin GVIA several times during an experiment and analysing the area s where injections affected respiratory activity, it was possible to m ap exactly the anatomical extent of the area critical for respiratory rhythm generation. 3. Following the precise localization of the pre-Bo tzinger complex with omega-conotoxin GVIA, we injected TTX to induce a n irreversible inactivation of this region. TTX injected unilaterally into the pre-Botzinger complex irreversibly reduced the amplitude of p hrenic nerve activity. Bilateral TTX injections eliminated respiratory rhythmic activity, causing a persistent central apnoea. 4. After bila teral lesioning of the pre-Botzinger complex, it was still possible to induce gasping during hypoxia or asphyxia, indicating that respiratio n and gasping are generated by two different neuronal networks. 5. We propose that omega-conotoxin GVIA as employed in this study to investi gate the functional role of the pre-Botzinger complex can also be used as a general pharmacological approach to map other neuronal networks. We call this the 'omega-conotoxin GVIA tracing' method.