Florey Department of Neuroscience and Mental Health - Research Publications

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    Activity of swallowing-related neurons in the medulla in the perfused brainstem preparation in rats
    Hashimoto, K ; Sugiyama, Y ; Fuse, S ; Umezaki, T ; Oku, Y ; Dutschmann, M ; Hirano, S (WILEY, 2019-02)
    OBJECTIVES/HYPOTHESIS: We aimed to investigate and validate the cellular activity patterns and the potential topographical organization of neurons of the medullary swallowing pattern generator (Sw-CPG). We used the perfused brainstem preparation as an innovative experimental model that allows for stable neuronal recording in the brainstem. STUDY DESIGN: Animal model. METHODS: Experiments were conducted in 14 juvenile Wistar rats. The activities of the phrenic, vagus, and hypoglossal nerves were recorded at baseline, and fictive swallowing was elicited by stimulation of the superior laryngeal nerve. Extracellular action potentials of 72 swallowing-related neurons were recorded in the Sw-CPG of the dorsal medulla oblongata. RESULTS: Neurons could be classified into three types: sensory relay, and neurons that were excited or inhibited during fictive swallowing. Approximately one-third of the neurons likely received monosynaptic input from the laryngeal afferents. One-third of neurons recorded showed respiratory-related activity, most of which exhibited inspiratory modulation. The neurons were widely distributed in the nucleus tractus solitarius and reticular formation. CONCLUSIONS: The perfused brainstem preparation of rat fully preserves the Sw-CPG. The recorded cellular activities and general topographical organization of swallowing neurons are in accordance with previous in vivo studies. Thus, the perfused brainstem preparation is an ideal experimental model to advance the understanding of neuronal mechanisms underlying swallowing. LEVEL OF EVIDENCE: NA Laryngoscope, 129:E72-E79, 2019.
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    Increasing Local Excitability of Brainstem Respiratory Nuclei Reveals a Distributed Network Underlying Respiratory Motor Pattern Formation
    Dhingra, RR ; Furuya, W ; Bautista, TG ; Dick, TE ; Galan, RF ; Dutschmann, M (FRONTIERS MEDIA SA, 2019-07-23)
    The core circuit of the respiratory central pattern generator (rCPG) is located in the ventrolateral medulla, especially in the pre-Bötzinger complex (pre-BötC) and the neighboring Bötzinger complex (BötC). To test the hypothesis that this core circuit is embedded within an anatomically distributed pattern-generating network, we investigated whether local disinhibition of the nucleus tractus solitarius (NTS), the Kölliker-Fuse nuclei (KFn), or the midbrain periaqueductal gray area (PAG) can similarly affect the respiratory pattern compared to disinhibition of the pre-BötC/BötC core. In arterially-perfused brainstem preparations of rats, we recorded the three-phase respiratory pattern (inspiration, post-inspiration and late-expiration) from phrenic and vagal nerves before and after bilateral microinjections of the GABA(A)R antagonist bicuculline (50 nl, 10 mM). Local disinhibition of either NTS, pre-BötC/BötC, or KFn, but not PAG, triggered qualitatively similar disruptions of the respiratory pattern resulting in a highly significant increase in the variability of the respiratory cycle length, including inspiratory and expiratory phase durations. To quantitatively analyze these motor pattern perturbations, we measured the strength of phase synchronization between phrenic and vagal motor outputs. This analysis showed that local disinhibition of all brainstem target nuclei, but not the midbrain PAG, significantly decreased the strength of phase synchronization. The convergent perturbations of the respiratory pattern suggest that the rCPG expands rostrally and dorsally from the designated core but does not include higher mid-brain structures. Our data also suggest that excitation-inhibition balance of respiratory network synaptic interactions critically determines the network dynamics that underlie vital respiratory rhythm and pattern formation.