Tonic Neuromodulation of the Inspiratory Rhythm Generator

The generation of neural network dynamics relies on the interactions between the intrinsic and synaptic properties of their neural components. Moreover, neuromodulators allow networks to change these properties and adjust their activity to specific challenges. Endogenous continuous (“tonic”) neuromodulation can regulate and sometimes be indispensible for networks to produce basal activity. This seems to be the case for the inspiratory rhythm generator located in the pre-Bötzinger complex (preBötC). This neural network is necessary and sufficient for generating inspiratory rhythms. The preBötC produces normal respiratory activity (eupnea) as well as sighs under normoxic conditions, and it generates gasping under hypoxic conditions after a reconfiguration process. The reconfiguration leading to gasping generation involves changes of synaptic and intrinsic properties that can be mediated by several neuromodulators. Over the past years, it has been shown that endogenous continuous neuromodulation of the preBötC may involve the continuous action of amines and peptides on extrasynaptic receptors. I will summarize the findings supporting the role of endogenous continuous neuromodulation in the generation and regulation of different inspiratory rhythms, exploring the possibility that these neuromodulatory actions involve extrasynaptic receptors along with evidence of glial modulation of preBötC activity.