Microglial modulators reduce respiratory rhythm long-term facilitation in vitro

Camacho-Hernández, Neira Polet; Lorea-Hernández, Jonathan Julio; Peña‐Ortega, Fernando

doi:10.1016/j.resp.2018.07.012

Cited by 21 publications

(25 citation statements)

References 99 publications

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“…Several other studies have investigated bath application of LPS on respiratory activity. Continuous bath application of LPS decreased respiratory activity in rhythmic slice preparations (Camacho-Hernández et al, 2019;Lorea-Hernández et al, 2016;Lu et al, 2012), although the effects on amplitude and frequency depended on the concentration. Similar to the results shown here, respiratory amplitude decreased after bath application of LPS (200 ng/ml LPS, Lorea-Hernández et al, 2016), while frequency decreased after 5 μg/ml bath-applied LPS (Lu et al, 2012), also demonstrating dose-dependent impairment in respiratory activity.…”

Section: Discussionmentioning

confidence: 90%

“…To understand the temporal and dose-dependency of systemic neonatal inflammation on respiratory activity, we investigated the effect of increasing LPS dose (0.1-10mg /kg) at 1h and 3h on fictive respiratory activity. Although neonatal infections can have deadly consequences (Heron, 2018) and neonatal respiratory impairment during infection is common (Campion et al, 2006;Fetter et al, 1995;Hofstetter et al, 2008;Ollikainen et al, 1993), the effect of neonatal inflammation on neural circuitry controlling breathing remains poorly understood (Camacho-Hernández et al, 2019;Lorea-Hernández et al, 2016;Lu et al, 2012). Further, we know little about the impact of timing and magnitude of early life inflammation on neonatal respiratory activity.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Time and dose-dependent impairment of neonatal respiratory motor activity after systemic inflammation

Morrison

Johnson

Hocker

et al. 2020

Respiratory Physiology & Neurobiology

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Time and dose-dependent impairment of neonatal respiratory motor activity after systemic inflammation

Morrison

Johnson

Hocker

et al. 2020

Respiratory Physiology & Neurobiology

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“…Thus, microglia are implicated in a wide range of processes, rendering these cells important contributors to the assembly and refinement of central neuronal circuits during ontogenesis. In the context of breathing control, the possible roles of microglia have so far been mainly investigated in relation to inflammatory responsiveness and its impact on rhythm generation, autoresuscitation, chemoreception and plasticity at post-natal ages (Huxtable et al, 2011; Huxtable et al, 2013; Tadmouri et al, 2014; Lorea-Hernandez et al, 2016; Camacho-Hernandez et al, 2019; Beyeler et al, 2020). Here, in a first description of the distribution and role of microglia in the embryonic hindbrain, we provide new data on the contribution of microglia to the early anatomical and functional development of brainstem networks responsible for respiratory rhythmogenesis.…”

Section: Discussionmentioning

confidence: 99%

Microglia shape the embryonic development of mammalian respiratory networks

Cabirol

Cardoit

Courtand

et al. 2022

Preprint

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Microglia, brain-resident macrophages, play key roles during prenatal development in defining neural circuitry function, including ensuring proper synaptic wiring and maintaining homeostasis. Mammalian breathing rhythmogenesis arises from interacting brainstem neural networks that are assembled during embryonic development, but the specific role of microglia in this process remains unknown. Here, we investigated the anatomical and functional consequences of respiratory circuit formation in the absence of microglia. We first established the normal distribution of microglia within the wild-type (WT, Pu.1+/+) mouse brainstem at embryonic ages when the respiratory networks are known to emerge (embryonic day (E) 14.5 for the parafacial respiratory group (epF) and E16.5 for the preBötzinger complex (preBötC)). In transgenic mice depleted of microglia (Pu.1-/- mutant), we performed anatomical staining, calcium imaging and electrophysiological recordings of neuronal activities in vitro to assess the status of these circuits at their respective times of functional emergence. Spontaneous respiratory-related activity recorded from reduced in vitro preparations showed an abnormally slow rhythm frequency expressed by the epF at E14.5, the preBötC at E16.5 and in the phrenic motor nerves from E16.5 onwards. These deficits were associated with a reduced number of active epF neurons, defects in commissural projections that couple the bilateral preBötC half-centers, and an accompanying decrease in their functional coordination. These abnormalities probably contribute to eventual neonatal death, since plethysmography revealed that E18.5 Pu.1-/- embryos are unable to sustain breathing activity ex utero. Our results thus point to a crucial contribution of microglia in the proper establishment of the central respiratory command during embryonic development.

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“…Microglia are the resident phagocytic and immunocompetent cells of the nervous system that have been mostly associated with pathological conditions (Eyo & Wu, 2019). However, normal functional communication between neurons and microglia is involved in a plethora of physiological processes during development and adulthood (Bessis et al, 2007; Kettenmann et al, 2013; Szepesi et al, 2018), including the regulation of neural network excitability (Camacho‐Hernández et al, 2019; Lorea‐Hernández et al, 2016). Microglia maintain close bidirectional interaction with neighboring neurons through a myriad of mediators including chemokines, neurotrophic factors, neurotransmitters and neuromodulators (Kettenmann et al, 2011; Pocock & Kettenmann, 2007; Szepesi et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…, including the regulation of neural network excitability (Camacho-Hernández et al, 2019;Lorea-Hernández et al, 2016). Microglia maintain close bidirectional interaction with neighboring neurons through a myriad of mediators including chemokines, neurotrophic factors, neurotransmitters and neuromodulators (Kettenmann et al, 2011;Pocock & Kettenmann, 2007;Szepesi et al, 2018).…”

mentioning

confidence: 99%

Abnormal innate and learned behavior induced by neuron–microglia miscommunication is related to CA3 reconfiguration

Méndez-Salcido

Torres-Flores

Ordaz

et al. 2022

Glia

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Neuron-microglia communication through the Cx3cr1-Cx3cl1 axis is essential for the development and refinement of neural circuits, which determine their function into adulthood. In the present work we set out to extend the behavioral characterization of Cx3cr1 À/À mice evaluating innate behaviors and spatial navigation, both dependent on hippocampal function. Our results show that Cx3cr1-deficient mice, which show some changes in microglial and synaptic terminals morphology and density, exhibit alterations in activities of daily living and in the rapid encoding of novel spatial information that, nonetheless, improves with training. A neural substrate for these cognitive deficiencies was found in the form of synaptic dysfunction in the CA3 region of the hippocampus, with a marked impact on the mossy fiber (MF) pathway. A network analysis of the CA3 microcircuit reveals the effect of these synaptic alterations on the functional connectivity among CA3 neurons with diminished strength and topological reorganization in Cx3cr1-deficient mice. Neonatal population activity of the CA3 region in Cx3cr1-deficient mice shows a marked reorganization around the giant depolarizing potentials, the first form of network-driven activity of the hippocampus, suggesting that alterations found in adult subjects arise early on in postnatal development, a critical period of microglia-dependent neural circuit refinement. Our results show that interruption of the Cx3cr1-Cx3cl1/neuronmicroglia axis leads to changes in CA3 configuration that affect innate and learned behaviors.

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Microglial modulators reduce respiratory rhythm long-term facilitation in vitro

Cited by 21 publications

References 99 publications

Time and dose-dependent impairment of neonatal respiratory motor activity after systemic inflammation

Time and dose-dependent impairment of neonatal respiratory motor activity after systemic inflammation

Microglia shape the embryonic development of mammalian respiratory networks

Abnormal innate and learned behavior induced by neuron–microglia miscommunication is related to CA3 reconfiguration

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