Development, generation, and origin of synchronous oscillations in the brainstem respiratory network
Neurons within the intact respiratory network are synchronized on long and short time scales to generate respiratory rhythm and synchronous oscillations in spike firing during inspiration (Figure 1.1), respectively. Such oscillations shape the pattern of inspiratory activity that leads to contractions of the inspiratory muscles. By recording inspiratory activity from the rhythmically mouse medullary slice, I investigated synchronous oscillations during postnatal development (P0-11), the role of inhibitory synaptic transmission in generating oscillations and examined where in the slice oscillations are produced.I found that average oscillation frequency significantly increased with postnatal development. Bath application of GABAA and GlyR antagonists significantly reduced synchronous oscillation power and increased peak integrated activity of inspiratory bursts in both neonates and juveniles. Bath application of Substance P alone, while increasing peak integrated activity, had no significant effect on oscillation power. Prolonging the time course of GABAergic synaptic currents with zolpidem decreased the median oscillation frequency. These data demonstrate that oscillation frequency increases with postnatal development and that both GABAergic and glycinergic transmission contribute to synchronization of motoneuron activity. Further, the time course of synaptic GABAergic currents is a determinant of oscillation frequency.Next, I tested the PreBotzinger Complex (PBC) and the XII nucleus as candidate regions in which oscillations are produced. Unilateral excitation of the PBC, via local perfusion of ACSF containing high K+, increased inspiratory burst frequency bilaterally, but had no effect on oscillation power recorded bilaterally. In contrast, unilateral excitation of the XII nucleus increased peak integrated activity bilaterally and oscillation power in the ipsilateral XII rootlet. Crosscorrelation analysis of control inspiratory activity recorded from the left and right XII rootlets produced crosscorrelation histograms with broad, significant peaks centered around a time lag of zero and no harmonic peaks. Coherence analysis of control left and right XII rootlet recordings demonstrated that oscillations are only weakly coherent. Together these data indicate that inspiratory-phase synchronous oscillations are generated in or immediately upstream of the XII motor nucleus. Collectively, my thesis research demonstrates a mechanism underlying the generation of synchronous oscillations and proposes a region of the simplified respiratory network in which these oscillations are produced.