Sigh and Eupnea Rhythmogenesis Involve Distinct Interconnected Subpopulations: A Combined Computational and...

Area of Science:

• Neuroscience
• Computational Neuroscience
• Respiratory Physiology

Background:

• Neural networks generate rhythmic outputs at various timescales for complex motor control.
• The pre-Bötzinger complex (preBötC) respiratory network produces both eupneic and sigh breaths, but the underlying mechanisms are unclear.

Purpose of the Study:

• To investigate the mechanisms of bimodal respiratory rhythm generation in the preBötC.
• To determine if distinct subnetworks or reconfiguring processes within a single network generate eupneic and sigh breaths.

Main Methods:

• Developed a two-compartment computational model of the preBötC based on in vitro mouse embryo data.
• Validated the model by comparing its output to experimental data, including the effects of blocking glycinergic synapses.
• Conducted in vitro experiments on isolated mouse brainstem slices to test model predictions.

Main Results:

• The model successfully reproduced simultaneous generation of sigh and eupnea with distinct characteristics.
• Sigh generation was found to be less sensitive to network excitability compared to eupneic activity.
• Calcium-dependent mechanisms and the Ih current were identified as crucial for sigh generation, with Ih activation parameters influencing excitability sensitivity.

Conclusions:

• The findings strongly support the hypothesis that distinct neuronal subpopulations within the preBötC are responsible for generating sigh and eupneic rhythms.
• This provides a mechanistic basis for the bimodal control of breathing patterns.