Inner ear lesion and the differential roles of hypoxia and hypercarbia in triggering active movements: Potential implication for the Sudden Infant Death Syndrome

Ramirez, Sanja; Allen, Travis; Villagracia, Lindsay; Chae, Yooree; Ramírez, Jan Marino; Rubens, Daniel

doi:10.1016/j.neuroscience.2016.08.054

Cited by 9 publications

(6 citation statements)

References 42 publications

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“…A major contributor to SIDS is the failure to arouse in response to hypoxic and hypercapnic conditions (Garcia, Koschnitzky, & Ramirez, ), which may occur when babies sleep in the prone position (Horne, Franco, Adamson, Groswasser, & Kahn, ). Much work on the neuropathology of SIDS has focused on the role of brainstem serotonin signaling (Haynes et al, ; Kinney, Richerson, Dymecki, Darnall, & Nattie, ), and the link to chemosensation (Buchanan, Smith, MacAskill, & Richerson, ; Ray et al, ), the hypoxic response of the respiratory network (J. M. Ramirez, Folkow, & Blix, ; S. Ramirez et al, ; Tryba, Pena, & Ramirez, ), and arousal (Buchanan & Richerson, ; Iwasaki et al, ; Mateika, Komnenov, Pop, & Kuhn, ). Yet many aspects of cardiorespiratory control also depend on cholinergic mechanisms, and are altered by nicotine exposure (Cerpa et al, ; Shao & Feldman, ; Vivekanandarajah, Waters, & Machaalani, ), including the respiratory chemosensory response (Coddou, Bravo, & Eugenin, ; Eugenin et al, ), and multiple aspects of upper airway control (Cholanian, Powell, Levine, & Fregosi, ; Cholanian, Wealing, Levine, & Fregosi, ; Powell, Levine, Frazier, & Fregosi, ; Wollman, Levine, & Fregosi, ).…”

Section: Discussionmentioning

confidence: 99%

Dual recombinase fate mapping reveals a transient cholinergic phenotype in multiple populations of developing glutamatergic neurons

Nasirova¹,

Quina²,

Agosto‐Marlin³

et al. 2019

J of Comparative Neurology

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Cholinergic transmission shapes the maturation of glutamatergic circuits, yet the developmental sources of acetylcholine have not been systematically explored. Here, we have used Cre‐recombinase‐mediated genetic labeling to identify and map both mature and developing CNS neurons that express choline acetyltransferase (ChAT). Correction of a significant problem with a widely used ChatCre transgenic line ensures that this map does not contain expression artifacts. ChatCre marks all known cholinergic systems in the adult brain, but also identifies several brain areas not usually regarded as cholinergic, including specific thalamic and hypothalamic neurons, the subiculum, the lateral parabrachial nucleus, the cuneate/gracilis nuclei, and the pontocerebellar system. This ChatCre fate map suggests transient developmental expression of a cholinergic phenotype in areas important for cognition, motor control, and respiration. We therefore examined expression of ChAT and the vesicular acetylcholine transporter in the embryonic and early postnatal brain to determine the developmental timing of this transient cholinergic phenotype, and found that it mirrored the establishment of relevant glutamatergic projection pathways. We then used an intersectional genetic strategy combining ChatCre with Vglut2Flp to show that these neurons adopt a glutamatergic fate in the adult brain. The transient cholinergic phenotype of these glutamatergic neurons suggests a homosynaptic source of acetylcholine for the maturation of developing glutamatergic synapses. These findings thus define critical windows during which specific glutamatergic circuits may be vulnerable to disruption by nicotine in utero, and suggest new mechanisms for pediatric disorders associated with maternal smoking, such as sudden infant death syndrome.

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Section: Discussionmentioning

confidence: 99%

Dual recombinase fate mapping reveals a transient cholinergic phenotype in multiple populations of developing glutamatergic neurons

Nasirova¹,

Quina²,

Agosto‐Marlin³

et al. 2019

J of Comparative Neurology

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“…Under hypoxic conditions, healthy mice show marked escape movements, but following ITG (which most probably disables the transient system selectively)—mice in the same hypoxic conditions show little escape movement (126–128). The neural pathways by which the transient system triggers escape behavior is not at all clear, but the possible significance of these results demands replication.…”

Section: Sustained and Transient Aspects Of Behavioral Responsesmentioning

confidence: 99%

Sustained and Transient Vestibular Systems: A Physiological Basis for Interpreting Vestibular Function

et al. 2017

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Otolithic afferents with regular resting discharge respond to gravity or low-frequency linear accelerations, and we term these the static or sustained otolithic system. However, in the otolithic sense organs, there is anatomical differentiation across the maculae and corresponding physiological differentiation. A specialized band of receptors called the striola consists of mainly type I receptors whose hair bundles are weakly tethered to the overlying otolithic membrane. The afferent neurons, which form calyx synapses on type I striolar receptors, have irregular resting discharge and have low thresholds to high frequency (e.g., 500 Hz) bone-conducted vibration and air-conducted sound. High-frequency sound and vibration likely causes fluid displacement which deflects the weakly tethered hair bundles of the very fast type I receptors. Irregular vestibular afferents show phase locking, similar to cochlear afferents, up to stimulus frequencies of kilohertz. We term these irregular afferents the transient system signaling dynamic otolithic stimulation. A 500-Hz vibration preferentially activates the otolith irregular afferents, since regular afferents are not activated at intensities used in clinical testing, whereas irregular afferents have low thresholds. We show how this sustained and transient distinction applies at the vestibular nuclei. The two systems have differential responses to vibration and sound, to ototoxic antibiotics, to galvanic stimulation, and to natural linear acceleration, and such differential sensitivity allows probing of the two systems. A 500-Hz vibration that selectively activates irregular otolithic afferents results in stimulus-locked eye movements in animals and humans. The preparatory myogenic potentials for these eye movements are measured in the new clinical test of otolith function—ocular vestibular-evoked myogenic potentials. We suggest 500-Hz vibration may identify the contribution of the transient system to vestibular controlled responses, such as vestibulo-ocular, vestibulo-spinal, and vestibulo-sympathetic responses. The prospect of particular treatments targeting one or the other of the transient or sustained systems is now being realized in the clinic by the use of intratympanic gentamicin which preferentially attacks type I receptors. We suggest that it is valuable to view vestibular responses by this sustained-transient distinction.

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“…This mechanism may be part of the processes which induce a person to move when there is a hypoxic condition. The role of this mechanism in Sudden Infant Death Syndrome (SIDS) has been considered as potentially relevant ( Allen et al, 2013 ; Ramirez et al, 2016 ). Also, a high expression level of NHE in the brain stem is associated with an increase in incidence of deaths by SIDS ( Wiemann et al, 2008 ).…”

Section: Evidence Of the Role Of H + In Synaptic Tmentioning

confidence: 99%

Protons as Messengers of Intercellular Communication in the Nervous System

Soto

Ortega-Ramírez

Vega

2018

Front. Cell. Neurosci.

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In this review, evidence demonstrating that protons (H+) constitute a complex, regulated intercellular signaling mechanisms are presented. Given that pH is a strictly regulated variable in multicellular organisms, localized extracellular pH changes may constitute significant signals of cellular processes that occur in a cell or a group of cells. Several studies have demonstrated that the low pH of synaptic vesicles implies that neurotransmitter release is always accompanied by the co-release of H+ into the synaptic cleft, leading to transient extracellular pH shifts. Also, evidence has accumulated indicating that extracellular H+ concentration regulation is complex and implies a source of protons in a network of transporters, ion exchangers, and buffer capacity of the media that may finally establish the extracellular proton concentration. The activation of membrane transporters, increased production of CO2 and of metabolites, such as lactate, produce significant extracellular pH shifts in nano- and micro-domains in the central nervous system (CNS), constituting a reliable signal for intercellular communication. The acid sensing ion channels (ASIC) function as specific signal sensors of proton signaling mechanism, detecting subtle variations of extracellular H+ in a range varying from pH 5 to 8. The main question in relation to this signaling system is whether it is only synaptically restricted, or a volume modulator of neuron excitability. This signaling system may have evolved from a metabolic activity detection mechanism to a highly localized extracellular proton dependent communication mechanism. In this study, evidence showing the mechanisms of regulation of extracellular pH shifts and of the ASICs and its function in modulating the excitability in various systems is reviewed, including data and its role in synaptic neurotransmission, volume transmission and even segregated neurotransmission, leading to a reliable extracellular signaling mechanism.

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Inner ear lesion and the differential roles of hypoxia and hypercarbia in triggering active movements: Potential implication for the Sudden Infant Death Syndrome

Cited by 9 publications

References 42 publications

Dual recombinase fate mapping reveals a transient cholinergic phenotype in multiple populations of developing glutamatergic neurons

Dual recombinase fate mapping reveals a transient cholinergic phenotype in multiple populations of developing glutamatergic neurons

Sustained and Transient Vestibular Systems: A Physiological Basis for Interpreting Vestibular Function

Protons as Messengers of Intercellular Communication in the Nervous System

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