Dataset Information

A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins.

ABSTRACT: Pain thresholds are, in part, set as a function of emotional and internal states by descending modulation of nociceptive transmission in the spinal cord. Neurons of the rostral ventromedial medulla (RVM) are thought to critically contribute to this process; however, the neural circuits and synaptic mechanisms by which distinct populations of RVM neurons facilitate or diminish pain remain elusive. Here we used in vivo opto/chemogenetic manipulations and trans-synaptic tracing of genetically identified dorsal horn and RVM neurons to uncover an RVM-spinal cord-primary afferent circuit controlling pain thresholds. Unexpectedly, we found that RVM GABAergic neurons facilitate mechanical pain by inhibiting dorsal horn enkephalinergic/GABAergic interneurons. We further demonstrate that these interneurons gate sensory inputs and control pain through temporally coordinated enkephalin- and GABA-mediated presynaptic inhibition of somatosensory neurons. Our results uncover a descending disynaptic inhibitory circuit that facilitates mechanical pain, is engaged during stress, and could be targeted to establish higher pain thresholds. VIDEO ABSTRACT.

SUBMITTER: Francois A

PROVIDER: S-EPMC7354674 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins.

François Amaury A Low Sarah A SA Sypek Elizabeth I EI Christensen Amelia J AJ Sotoudeh Chaudy C Beier Kevin T KT Ramakrishnan Charu C Ritola Kimberly D KD Sharif-Naeini Reza R Deisseroth Karl K Delp Scott L SL Malenka Robert C RC Luo Liqun L Hantman Adam W AW Scherrer Grégory G

Neuron 20170202 4

Pain thresholds are, in part, set as a function of emotional and internal states by descending modulation of nociceptive transmission in the spinal cord. Neurons of the rostral ventromedial medulla (RVM) are thought to critically contribute to this process; however, the neural circuits and synaptic mechanisms by which distinct populations of RVM neurons facilitate or diminish pain remain elusive. Here we used in vivo opto/chemogenetic manipulations and trans-synaptic tracing of genetically ident ...[more]

PMID: 28162807

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Project description:Key pointsInhibitory-interneuron networks, consisting of multiple forms of circuit motifs including reciprocal (inhibitory interneurons inhibiting other interneurons) and feedforward (inhibitory interneurons inhibiting principal neurons) connections, are crucial in processing sensory information. The present study applies a statistical method to in vivo multichannel spike trains of dorsal cochlear nucleus neurons to disentangle reciprocal and feedforward-inhibitory motifs. After inducing input-specific plasticity, reciprocal and feedforward inhibition are found to be differentially regulated, and the combined effect synergistically modulates circuit output. The findings highlight the interplay among different circuit motifs as a key element in neural computation.AbstractInhibitory interneurons play an essential role in neural computations by utilizing a combination of reciprocal (interneurons inhibiting each other) and feedforward (interneuron inhibiting the principal neuron) inhibition to process information. To disentangle the interplay between the two inhibitory-circuit motifs and understand their effects on the circuit output, in vivo recordings were made from the guinea pig dorsal cochlear nucleus, a cerebellar-like brainstem circuit. Spikes from inhibitory interneurons (cartwheel cell) and principal output neurons (fusiform cell) were compared before and after manipulating their common multimodal input. Using a statistical model based on the Cox method of modulated renewal process of spike train influence, reciprocal- and feedforward-inhibition motifs were quantified. In response to altered multimodal input, reciprocal inhibition was strengthened while feedforward inhibition was weakened, and the two motifs combined to modulate fusiform cell output and acoustic-driven responses. These findings reveal the cartwheel cell's role in auditory and multimodal processing, as well as illustrated the balance between different inhibitory-circuit motifs as a key element in neural computation.

Dataset Information

A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins.

Publications

A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins.

Similar Datasets

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