Optoactivation of parvalbumin neurons in the spinal dorsal horn evokes GABA release that is regulated by presynaptic GABAB receptors

Yang, Kun; Ma, Rui; Wang, Qian; Jiang, Ping; Li, Yunqing

doi:10.1016/j.neulet.2015.03.050

Cited by 25 publications

(14 citation statements)

References 33 publications

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“…9 In laminae I-II, electrophysiological studies performed in rat demonstrated that the exogenous or endogenous activation of presynaptic GABA B Rs inhibits the release of peptides and glutamate from the primary afferent terminals of Aδ and C types 5,10–14 and decreases the release of GABA and glycine from the spinal inhibitory interneurons. 14–16 The depression of neurotransmitter release mediated by GABA B Rs derives from the concurrent inhibition of presynaptic calcium channels 17–19 and release machinery downstream Ca 2+ entry into the nerve terminals. 20 …”

Section: Introductionmentioning

confidence: 99%

GABA_B receptors-mediated tonic inhibition of glutamate release from Aβ fibers in rat laminae III/IV of the spinal cord dorsal horn

2017

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Presynaptic GABAB receptors (GABABRs) are highly expressed in dorsal root ganglion neurons and spinal cord dorsal horn. GABABRs located in superficial dorsal horn play an important antinociceptive role, by acting at both pre- and postsynaptic sites. GABABRs expressed in deep dorsal horn could be involved in the processing of touch sensation and possibly in the generation of tactile allodynia in chronic pain. The objective of this study was to characterize the morphological and functional properties of GABABRs expressed on Aβ fibers projecting to lamina III/IV and to understand their role in modulating excitatory synaptic transmission. We performed high-resolution electron microscopic analysis, showing that GABAB2 subunit is expressed on 71.9% of terminals in rat lamina III-IV. These terminals were engaged in axodendritic synapses and, for the 46%, also expressed glutamate immunoreactivity. Monosynaptic excitatory postsynaptic currents, evoked by Aβ fiber stimulation and recorded from lamina III/IV neurons in spinal cord slices, were strongly depressed by application of baclofen (0.1–2.5 µM), acting as a presynaptic modulator. Application of the GABABR antagonist CGP 55845 caused, in a subpopulation of neurons, the potentiation of the first of two excitatory postsynaptic currents recorded with the paired-pulse protocol, showing that GABABRs are endogenously activated. A decrease in the paired-pulse ratio accompanied the effect of CGP 55845, implying the involvement of presynaptic GABABRs. CGP 55845 facilitated only the first excitatory postsynaptic current also during a train of four consecutive stimuli applied to Aβ fibers. These results suggest that GABABRs tonically inhibit glutamate release from Aβ fibers at a subset of synapses in deep dorsal horn. This modulation specifically affects only the early phase of synaptic excitation in lamina III-IV neurons.

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Section: Introductionmentioning

confidence: 99%

GABA_B receptors-mediated tonic inhibition of glutamate release from Aβ fibers in rat laminae III/IV of the spinal cord dorsal horn

2017

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“…While this approach has been very powerful in the brain (Adamantidis et al, 2015; Boyden, 2015; Deisseroth, 2015), and peripheral nervous system (Copits et al, 2016; Iyer et al, 2014; Montgomery et al, 2016), the application of optogenetic control in the mammalian spinal cord has been largely restricted to ex vivo slice preparations (Carr and Zachariou, 2014; Dougherty et al, 2013; Foster et al, 2015; Hägglund et al, 2013, 2010; Talpalar et al, 2011; Wang and Zylka, 2009; Yang et al, 2015; Zhang et al, 2014), which do not allow for direct analysis of the behavioral consequences of neural control.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Interrogation of Spinal Mechanosensory Circuits

et al. 2016

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Summary Spinal dorsal horn circuits receive, process, and transmit somatosensory information. To understand how specific components of these circuits contribute to behavior, it is critical to be able to directly modulate their activity in unanesthetized in vivo conditions. Here, we develop experimental tools that enable optogenetic control of spinal circuitry in freely moving mice using commonly available materials. We use these tools to examine mechanosensory processing in the spinal cord, and observe that optogenetic activation of somatostatin+ interneurons facilitates both mechanosensory and itch-related behavior, while reversible chemogenetic inhibition of these neurons suppresses mechanosensation. These results extend recent findings regarding processing of mechanosensory information in the spinal cord and indicate the potential for activity-induced release of the somatostatin neuropeptide to affect processing of itch. The spinal implant approach we describe here is likely to enable a wide range of studies to elucidate spinal circuits underlying pain, touch, itch, and movement.

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“…Transgenic animals allowing for optogenetic modulation of either spinal (Yang et al . ) or peripheral (Towne et al . ) neurons have enabled the activation of neural circuits to a level of precision not previously possible.…”

Section: Discussionmentioning

confidence: 99%

“…; Abraira & Ginty, ) and is composed of a series of functionally distinct laminae, cytoarchitecturally classified (Sengul, ), which have been investigated with a range of techniques to help understand their functions and interactions (Yang et al . ; Ran et al . ; Hachisuka et al .…”

Section: Introductionmentioning

confidence: 99%

“…The dorsal horn (DH) of the spinal cord is the primary site of sensory processing within the central nervous system Abraira & Ginty, 2013) and is composed of a series of functionally distinct laminae, cytoarchitecturally classified (Sengul, 2015), which have been investigated with a range of techniques to help understand their functions and interactions (Yang et al 2015;Ran et al 2016;Hachisuka et al 2016). The DH receives sensory information from cutaneous and visceral structures via primary afferent neurons and is also the target of descending projections emanating from structures within the brain, particularly the brainstem, that modulate spinal excitability (Hathway et al 2009).…”

Section: Introductionmentioning

confidence: 99%

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Lamina‐specific population encoding of cutaneous signals in the spinal dorsal horn using multi‐electrode arrays

Greenspon

Battell

Devonshire

et al. 2018

The Journal of Physiology

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Key points Traditional, widely used in vivo electrophysiological techniques for the investigation of spinal processing of somatosensory information fail to account for the diverse functions of each lamina.To overcome this oversimplification, we have used multi‐electrode arrays, in vivo, to simultaneously record neuronal activity across all laminae of the spinal dorsal horn.Multi‐electrode arrays are sensitive enough to detect lamina‐ and region‐specific encoding of different subtypes of afferent fibres and to detect short‐lived changes in synaptic plasticity as measured by the application of cutaneous electrical stimulation of varying intensity and frequency.Differential encoding of innocuous and noxious thermal and mechanical stimuli were also detected across the laminae with the technique, as were the effects of the application of capsaicin.This new approach to the study of the dorsal spinal cord produces significantly more information per experiment, permitting accelerated research whilst also permitting the effects of pharmacological tools to modulate network responses. AbstractThe dorsal horn (DH) of the spinal cord is a complex laminar structure integrating peripheral signals into the central nervous system. Spinal somatosensory processing is commonly measured electrophysiologically in vivo by recording the activity of individual wide‐dynamic‐range neurons in the deep DH and extrapolating their behaviour to all cells in every lamina. This fails to account for the specialized processes that occur in each lamina and the considerable heterogeneity in cellular phenotype within and between laminae. Here we overcome this oversimplification by employing linear multi‐electrode arrays (MEAs) in the DH of anaesthetized rats to simultaneously measure activity across all laminae. The MEAs, comprising 16 channels, were inserted into the lumbar dorsal horn and peripheral neurons activated electrically via transcutaneous electrodes and ethologically with von Frey hairs (vFHs) or an aluminium heating block. Ascending electrical stimuli showed fibre thresholds with distinct dorsoventral innervation profiles. Wind up was observed across the DH during the C‐fibre and post‐discharge latencies following 0.5 Hz stimulation. Intrathecal application of morphine (5 ng/50 μl) significantly reduced Aδ‐ and C‐fibre‐evoked activity in deep and superficial DH. Light vFHs (≤10 g) predominantly activated intermediate and deep laminae whereas noxious vFHs (26 g) also activated the superficial laminae. Noxious heat (55°C) induced significantly greater activity in the superficial and deep laminae than the innocuous control (30°C). The application of these arrays produced the first description of the processing of innocuous and noxious stimuli throughout the intact DH.

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Optoactivation of parvalbumin neurons in the spinal dorsal horn evokes GABA release that is regulated by presynaptic GABAB receptors

Cited by 25 publications

References 33 publications

GABA_B receptors-mediated tonic inhibition of glutamate release from Aβ fibers in rat laminae III/IV of the spinal cord dorsal horn

GABA_B receptors-mediated tonic inhibition of glutamate release from Aβ fibers in rat laminae III/IV of the spinal cord dorsal horn

In Vivo Interrogation of Spinal Mechanosensory Circuits

Lamina‐specific population encoding of cutaneous signals in the spinal dorsal horn using multi‐electrode arrays

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Optoactivation of parvalbumin neurons in the spinal dorsal horn evokes GABA release that is regulated by presynaptic GABAB receptors

Cited by 25 publications

References 33 publications

GABAB receptors-mediated tonic inhibition of glutamate release from Aβ fibers in rat laminae III/IV of the spinal cord dorsal horn

GABAB receptors-mediated tonic inhibition of glutamate release from Aβ fibers in rat laminae III/IV of the spinal cord dorsal horn

In Vivo Interrogation of Spinal Mechanosensory Circuits

Lamina‐specific population encoding of cutaneous signals in the spinal dorsal horn using multi‐electrode arrays

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Product

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GABA_B receptors-mediated tonic inhibition of glutamate release from Aβ fibers in rat laminae III/IV of the spinal cord dorsal horn

GABA_B receptors-mediated tonic inhibition of glutamate release from Aβ fibers in rat laminae III/IV of the spinal cord dorsal horn