The disruptive respiratory effects of neurotoxic destruction of the pre‐Botzinger complex are not exacerbated during sleep

Abstract

Bilateral injection of a ribosomal neurotoxin into the pre‐Botzinger complex (PBC) of rats disrupts breathing first in REM sleep, then days thereafter during NREM sleep, and eventually during wakefulness (Nat Neurosci. 9:1142–4, 2005). We test the hypothesis that incremental destruction of the PBC also leads to a state‐dependent disruption in breathing. Microtubules were bilaterally implanted into the PBC of 5 adult goats. After recovery and baseline parameters were established, increasing volumes (0.5, 1, 5, and 10uL) of ibotenic acid (IA) (50mM) were injected into the PBC, with one week between injections. Goats were studied for 5 hours post injection (accompanying abstract) and each night 9 to 14 hours after injection. Minutes after each injection, breathing frequency increased and eupneic airflow and respiratory muscle pattern were disrupted. Then, 9–14 hours post injection, these disruptions were most pronounced during the awake state, and less during NREM and REM sleep. One week after the 10uL injection, breathing pattern and blood gases did not differ between state, or from pre‐IA control. Histological analysis showed >85% destruction of the PBC. Thus, after incremental destruction of the PBC, plasticity within the respiratory network provides a respiratory rhythm appropriate to sustain homeostasis during awake, NREM, and REM states. (Supported by the Department of Veterans Affairs and NIH HL25739)