Central Sensory Neurons Detect and Combat Pathogens Invading the Cerebrospinal Fluid

Prendergast, Andrew; Jim, Kin Ki; Marnas, Hugo; Desban, Laura; Quan, Feng B.; Djenoune, Lydia; Roussel, Julian; Cantaut-Belarif, Yasmine; Sahu, Shubham; Bardet, Pierre-Luc; Beek, Diederik van de; Vandenbroucke-Grauls, Christina M. J. E.; Wyart, Claire

doi:10.2139/ssrn.3404255

Cited by 5 publications

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“…Although mechanosensory signals would be generated during treadmill locomotion or ladder walking, these should be further investigated in future studies. Other chemosensory signals, such as pH changes or compounds proposed to be generated in respiratory changes, excess neural activities, fatigue, autonomic, or immune responses, may also be involved ( Huang et al, 2006 ; Jalalvand et al, 2016b ; Prendergast et al, 2019 ). Such signals are currently poorly understood in mammals.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid-contacting neuron tracing reveals structural and functional connectivity for locomotion in the mouse spinal cord

Nakamura

Kurabe

Matsumoto

et al. 2023

eLife

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Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lying along the central canal of the spinal cord. Recent studies in zebrafish larvae and lampreys have shown that CSF-cNs control postures and movements via spinal connections. However, the structures, connectivity, and functions in mammals remain largely unknown. Here we developed a method to genetically target mouse CSF-cNs that highlighted structural connections and functions. We first found that intracerebroventricular injection of adeno-associated virus with a neuron-specific promoter and Pkd2l1-Cre mice specifically labeled CSF-cNs. Single-cell labeling of 71 CSF-cNs revealed rostral axon extensions of over 1800 μm in unmyelinated bundles in the ventral funiculus and terminated on CSF-cNs to form a recurrent circuitry, which was further determined by serial electron microscopy and electrophysiology. CSF-cNs were also found to connect with axial motor neurons and premotor interneurons around the central canal and within the axon bundles. Chemogenetic CSF-cNs inactivation reduced speed and step frequency during treadmill locomotion. Our data revealed the basic structures and connections of mouse CSF-cNs to control spinal motor circuits for proper locomotion. The versatile methods developed in this study will contribute to further understanding of CSF-cN functions in mammals.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid-contacting neuron tracing reveals structural and functional connectivity for locomotion in the mouse spinal cord

Nakamura

Kurabe

Matsumoto

et al. 2023

eLife

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“…5 CSF-cNs form inhibitory synapses onto presynaptic boutons of the Mauthner cell axons that are the site of action potential propagation and presynaptic release. 81,82 At baseline, CSF-cNs exhibit low levels of asynchronous firing 34,103 that could hyperpolarize the Mauthner presynaptic boutons and enhance synaptic release via a mechanism known as hyperpolarization-induced analog-digital facilitation. 104 In brief, a hyperpolarization of the presynaptic site can enhance excitatory postsynaptic potentials (EPSPs) of postsynaptic cells via an increase of the calcium influx in the Mauthner cell presynaptic bouton, leading to a larger depolarization and faster spiking of MNs.…”

Section: Csf-cn Mechanosensory Feedback Can Modulate Descending Commands From the Hindbrain To The Spinal Cordmentioning

confidence: 99%

Spinal sensory neurons project onto the hindbrain to stabilize posture and enhance locomotor speed

Carbó-Tano

Mirat

et al. 2021

Current Biology

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“…Although mechanosensory signals would be generated during treadmill locomotion, these should be further investigated in future studies. Other chemosensory signals such as pH changes or compounds proposed to be generated in respiratory changes, excess neural activities, fatigue, autonomic, or immune responses, may also be involved (Huang et al, 2006; Jalalvand et al, 2016b; Prendergast et al, 2021). Such signals are currently poorly understood in mammals.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid-contacting neuron tracing reveals structural and functional connectivity for locomotion in the mouse spinal cord

Nakamura

Kurabe

Matsumoto

et al. 2022

Preprint

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Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lying along the central canal of the spinal cord. Recent studies in zebrafish larvae and lampreys have shown that CSF-cNs control postures and movements via spinal connections. However, the structures, connectivity, and functions in mammals remain largely unknown. Here we developed a method to genetically target mouse CSF-cNs that highlighted structural connections and functions. We first found that intracerebroventricular injection of adeno-associated virus with a neuron-specific promoter and Pkd2l1-Cre mice specifically labeled CSF-cNs. Single-cell labeling of 71 CSF-cNs revealed rostral axon extensions of over 1800 um in unmyelinated bundles in the ventral funiculus and terminated on CSF-cNs to form a recurrent circuitry, which was further determined by serial electron microscopy and electrophysiology. CSF-cNs were also found to connect with axial motor neurons and premotor interneurons around the central canal and within the axon bundles. Chemogenetic CSF-cNs inactivation reduced speed and step frequency during treadmill locomotion. Our data revealed the basic structures and connections of mouse CSF-cNs to control spinal motor circuits for proper locomotion. The versatile methods developed in this study will contribute to further understanding of CSF-cNs functions in mammals.

show abstract

Central Sensory Neurons Detect and Combat Pathogens Invading the Cerebrospinal Fluid

Cited by 5 publications

References 0 publications

Cerebrospinal fluid-contacting neuron tracing reveals structural and functional connectivity for locomotion in the mouse spinal cord

Cerebrospinal fluid-contacting neuron tracing reveals structural and functional connectivity for locomotion in the mouse spinal cord

Spinal sensory neurons project onto the hindbrain to stabilize posture and enhance locomotor speed

Cerebrospinal fluid-contacting neuron tracing reveals structural and functional connectivity for locomotion in the mouse spinal cord

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