Research

Breathing is a vital, automatic behavior that begins at birth and continues throughout life. Still, the neuronal circuits that generate and regulate this rhythmic activity are not fully understood. Clinical conditions such as unstable breathing in neonates, anesthesia-induced respiratory suppression, and age-related respiratory disorders highlight the importance of understanding how these networks are organized and how they develop over time.

We investigate how rhythmic breathing is generated by neuronal circuits in the brainstem, and how these circuits develop and mature during the perinatal period. We previously proposed a functional microcircuit structure within the preBötzinger complex (preBötC), a critical component of the respiratory center, based on time-series analysis of neuronal activities during inspiration (Oke et al., 2018). More recently, we showed that this microcircuit undergoes significant developmental changes during early postnatal life (Oke et al., 2023), suggesting a dynamic maturation process that enhances the robustness of respiratory output after birth.

Currently, we are addressing two key questions:

• How do GAD67 neurons contribute to respiratory control in the mature network?

  We use chemogenetic tools (DREADDs) to selectively regulate the activity of GAD67 neurons and examine their roles. Dysfunction of GABAergic signaling has been linked to respiratory issues in clinical settings, such as anesthetic-induced suppression. By unraveling the cellular and circuit mechanisms of GAD67 neurons, our research aims to provide foundational insights that may guide future strategies for managing disordered breathing.

• What roles do GAD67 neurons play in the development of respiratory networks during the fetal period?

  Mice lacking GAD67 die shortly after birth due to respiratory failure. We aim to clarify how fetal GABAergic activity contributes to the formation of respiratory networks.

Through this research, we aim to uncover fundamental principles of neural rhythmogenesis and contribute to understanding the neural basis of breathing disorders across the lifespan.