1. Electrical stimulation (10 s) of the ethmoidal nerve (EN5) evokes the nasotrigeminal reflex responses, including apnoea, bradycardia and rise in arterial blood pressure. In the present study, we examined the involvement of N-methyl-ª_aspartate (NMDA), AMPAÏkainate, (ã_aminobutyric acidA (GABAA) and glycine receptors in the K olliker-Fuse (KF) nucleus in the mediation of the nasotrigeminal reflex responses. 2. Unilateral injections (n = 6) of 50-100 nl of the NMDA receptor antagonist AP5 into the KF area led to a significant blockade of the EN5-evoked respiratory depression and bradycardia. Injections placed into the midlevel of the KF area were most effective (80-90% blockade). The rise in arterial blood pressure remained unaffected. 3. Unilateral injections (n = 6) of the AMPAÏkainate receptor antagonist CNQX into the KF area failed to block EN5-evoked autonomic responses significantly. 4. Unilateral injections (n = 5) of the GABAA receptor antagonist bicuculline enhanced the EN5-evoked respiratory depression and bradycardia. The effect persisted for up to 30 s after stimulation. Bicuculline injections into the midlevel of the KF area were most effective. The increase in arterial blood pressure remained unaffected. 5. Unilateral injections (n = 5) of the glycine receptor antagonist strychnine into the KF area did not produce any significant effects on EN5-evoked autonomic responses. 6. Our results suggest that the KF area represents a mandatory relay for the nasotrigeminally induced apnoea and bradycardia which are predominantly mediated by NMDA receptors in the KF. Furthermore, it appears that KF neurons are under a potent GABAergic inhibitory control. The EN5-evoked rise in arterial blood pressure was not altered by any of the drugs and, therefore, appears not to be mediated via the KF.

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Dutschmann, Mathias, and Julian F. R. Paton. Trigeminal reflex regulation of the glottis depends on central glycinergic inhibition in the rat. Am J Physiol Regulatory Integrative Comp Physiol 282: R999-R1005, 2002; 10.1152/ ajpregu.00502.2001.-In an unanesthetized decerebrate in situ arterially perfused brain stem preparation of mature rat, strychnine (0.05-0.2 M) blockade of glycine receptors caused postinspiratory glottal constriction to occur earlier, shifting from early expiration to inspiration. This resulted in a paradoxical inspiratory-related narrowing of the upper airway. Stimulation of the trigeminal ethmoidal nerve (EN5; 20 Hz, 100 s, 0.5-2 V) evoked a diving response, which included a reflex apnea, glottal constriction, and bradycardia. After strychnine administration, this pattern was converted to a maintained phrenic nerve discharge and a reduced glottal constriction that was interrupted intermittently by transient abductions. The onset of firing of postinspiratory neurons shifted from early expiration into neural inspiration in the presence of strychnine, but neurons maintained their tonic activation during EN5 stimulation, as observed during control. Inspiratory neurons that were hyperpolarized by EN5 stimulation in control conditions were powerfully excited after loss of glycinergic inhibition. Thus the integrity of glycinergic inhibition within the pontomedullary respiratory network is critical for the coordination of cranial and spinal motor outflows during eupnea but also for protective reflex regulation of the upper airway.ventral respiratory group; upper airway patency; synaptic inhibition; diving response THE NETWORK MODEL for respiratory rhythm generation comprises three phases of respiration: inspiration, postinspiration, and expiration. During eupnea, there is a respiratory modulation of the upper airway such that the vocal fold is dilated (abducted) to decrease airway resistance during inspiration and constricted (adducted) during early expiration or postinspiration. This postinspiratory glottal constriction is particularly important for slowing expiratory airflow out of the lungs to allow time for efficient gas exchange and to maintain functional residual capacity, thereby preventing lung collapse (for review, see Ref. In the mammal one of the most potent upper airway protective reflexes occurs during diving. Activation of nasotrigeminal afferents evokes a diving response (7, 17) that includes a profound constriction of the glottis (15) to ensure that water cannot enter the bronchi. In the present study, we assessed the role of central glycinergic neurotransmission for the functional integrity of upper airway adduction during the diving response. We show that both the ongoing eupneic modulation of the upper airway and the reflexly evoked glottic closure during a diving response are massively disrupted after blockade of glycinergic neurotransmission. MATERIALS AND METHODS Preparation of animals.Experiments were performed on mature rats (Wistar, 70-100 g) of either sex. We employed the...

Key pointsr The functional neuroanatomy of the mammalian respiratory network is far from being understood since experimental tools that measure neural activity across this brainstem-wide circuit are lacking.r Here, we use silicon multi-electrode arrays to record respiratory local field potentials (rLFPs) from 196-364 electrode sites within 8-10 mm 3 of brainstem tissue in single arterially perfused brainstem preparations with respect to the ongoing respiratory motor pattern of inspiration (I), post-inspiration (PI) and late-expiration (E2). r rLFPs peaked specifically at the three respiratory phase transitions, E2-I, I-PI and PI-E2. r We show, for the first time, that only the I-PI transition engages a brainstem-wide network, and that rLFPs during the PI-E2 transition identify a hitherto unknown role for the dorsal respiratory group.r Volumetric mapping of pontomedullary rLFPs in single preparations could become a reliable tool for assessing the functional neuroanatomy of the respiratory network in health and disease.Abstract While it is widely accepted that inspiratory rhythm generation depends on the pre-Bötzinger complex, the functional neuroanatomy of the neural circuits that generate expiration is debated. We hypothesized that the compartmental organization of the brainstem respiratory network is sufficient to generate macroscopic local field potentials (LFPs), and if so, respiratory (r) LFPs could be used to map the functional neuroanatomy of the respiratory network. We developed an approach using silicon multi-electrode arrays to record spontaneous LFPs from hundreds of electrode sites in a volume of brainstem tissue while monitoring the Rishi R. Dhingra is currently a Senior Research Officer in the Florey Institute of Neuroscience & Mental Health at the University of Melbourne. He received his PhD in Neurosciences in 2014 from Case Western Reserve University, Cleveland, USA. His research interest is to develop and apply innovative approaches to monitor and model the activity of brainstem respiratory and cardiovascular circuits at the systems scale in vertebrates. J Physiol 598.11 respiratory motor pattern on phrenic and vagal nerves in the perfused brainstem preparation. Our results revealed the expression of rLFPs across the pontomedullary brainstem. rLFPs occurred specifically at the three transitions between respiratory phases: (1) from late expiration (E2) to inspiration (I), (2) from I to post-inspiration (PI), and (3) from PI to E2. Thus, respiratory network activity was maximal at respiratory phase transitions. Spatially, the E2-I, and PI-E2 transitions were anatomically localized to the ventral and dorsal respiratory groups, respectively. In contrast, our data show, for the first time, that the generation of controlled expiration during the post-inspiratory phase engages a distributed neuronal population within ventral, dorsal and pontine network compartments. A group-wise independent component analysis demonstrated that all preparations exhibited rLFPs with a similar temporal structure and thu...

The coronavirus disease 2019 (COVID-19) outbreak in North, Central, and South America has become the epicenter of the current pandemic. We have suggested previously that the infection rate of this virus might be lower in people living at high altitude (over 2,500 m) compared to that in the lowlands. Based on data from official sources, we performed a new epidemiological analysis of the development of the pandemic in 23 countries on the American continent as of May 23, 2020. Our results confirm our previous finding, further showing that the incidence of COVID-19 on the American continent decreases significantly starting at 1,000 m above sea level (masl). Moreover, epidemiological modeling indicates that the virus transmission rate is lower in the highlands (>1,000 masl) than in the lowlands (<1,000 masl). Finally, evaluating the differences in the recovery percentage of patients, the death-to-case ratio, and the theoretical fraction of undiagnosed cases, we found that the severity of COVID-19 is also decreased above 1,000 m. We conclude that the impact of the COVID-19 decreases significantly with altitude.