Kv3.1b and Kv3.3 channel subunit expression in murine spinal dorsal horn GABAergic interneurones

Nowak, Anna K.; Mathieson, Hannah R.; Chapman, Rebecca; Janzsó, G.; Yanagawa, Yuchio; Obata, Kunihiko; Szabó, Gábor; King, Anne E.

doi:10.1016/j.jchemneu.2011.02.003

Cited by 14 publications

(21 citation statements)

References 46 publications

(47 reference statements)

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“…In our experiments, neurons in lamina II labeled genetically with eGFP under the GAD-65 promoter exhibited three distinct firing modes in response to depolarizing pulses (initial, tonic, and gap/delay). Previous work using either genetic labeling or peptide co-localization suggested that delayed or gap firing is a hallmark of excitatory interneurons, while tonic firing is more characteristic of inhibitory interneurons (Heinke et al 2004; Nowak et al 2011; Punnakkal et al 2014; Yasaka et al 2010), however our data indicate that nearly a quarter of neurons labeled in the GAD-65 reporter mouse exhibit delayed/gap firing. Here we have referred to these neurons as GABAergic for convenience, but recognize that approximately 20% of our recordings likely represent another cell class since approximately 80% of neurons labeled in this mouse are GABA immunopositive (Cui et al 2011).…”

Section: Discussioncontrasting

confidence: 81%

“…Notably, in GAD-65 mice only 60% of all lamina II GABAergic neurons are labelled, suggesting that studies using GAD-67 labeled neurons likely only sample a partially overlapping population (Cui et al 2011). GAD-65 labeled neurons (unlike most GAD-67 labeled cells) co-express c-fos after treatment with peripheral capsaicin, however, emphasizing the likely participation of the GAD-65 neurons we used in peripheral inflammatory processes (Nowak et al 2011).…”

Section: Discussionmentioning

confidence: 98%

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NMDA receptor activation induces long-term potentiation of glycine synapses

Kloc

Pradier

Chirila

et al. 2019

Preprint

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Of the fast ionotropic synapses, glycinergic synapses are the least well understood, but are vital for the maintenance of inhibitory signaling in the brain and spinal cord. Glycinergic signaling comprises half of the inhibitory signaling in the spinal cord, and glycinergic synapses are likely to regulate local nociceptive processing as well as the transmission to the brain of peripheral nociceptive information. Here we have investigated the rapid and prolonged potentiation of glycinergic synapses in the superficial dorsal horn of young male and female mice after brief activation of NMDA receptors (NMDARs). Glycinergic inhibitory postsynaptic currents (IPSCs) evoked with lamina II-III stimulation in identified GABAergic neurons in lamina II were potentiated by bath-applied Zn 2+ and were depressed by the prostaglandin PGE2, consistent with the presence of both GlyRα1-and GlyRα3-containing receptors. NMDA application rapidly potentiated synaptic glycinergic currents. Whole-cell currents evoked by exogenous glycine were also rapidly potentiated by NMDA, indicating that the potentiation results from altered numbers or conductance of postsynaptic glycine receptors. Repetitive depolarization alone of the postsynaptic GABAergic neuron also potentiated glycinergic synapses, and intracellular EGTA prevented both NMDA-induced and depolarization-induced potentiation of glycinergic IPSCs. Driving trpv1 lineage afferents optogenetically also triggered NMDAR-dependent potentiation of glycinergic synapses. Our results suggest that during peripheral injury or inflammation, nociceptor firing during injury is likely to potentiate glycinergic synapses on GABAergic neurons. This disinhibition mechanism may be engaged rapidly, altering dorsal horn circuitry to promote the transmission of nociceptive information to the brain. Significance:Of the fast ionotropic synapses, glycinergic synapses are the least well understood, yet glycinergic synapses comprise half of the inhibition in the spinal cord, and are likely to regulate local nociceptive processing as well as the transmission to the brain of peripheral nociceptive information. Here we report that bath applied NMDA, repetitive postsynaptic depolarization, or optogenetic activation of primary nociceptor afferents all produce LTP at superficial dorsal horn synapses. During peripheral injury or inflammation, nociceptor firing is likely to engage this mechanism in inhibitory neurons, rapidly altering dorsal horn circuitry to promote the transmission of nociceptive information to the brain.

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Section: Discussioncontrasting

confidence: 81%

Section: Discussionmentioning

confidence: 98%

NMDA receptor activation induces long-term potentiation of glycine synapses

Kloc

Pradier

Chirila

et al. 2019

Preprint

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“…As expected from their electrophysiological properties, Kv3.3 channels are expressed in neurons that fire at high rates, particularly in the brainstem and cerebellum (Li et al 2001;Chang et al 2007;Puente et al 2010). High levels are also found in inhibitory parvalbumin-containing cortical interneurons that typically are capable of firing at hundreds of hertz, as well as in GABA-ergic interneurons in other parts of the nervous system (Chang et al 2007;Alonso-Espinaco et al 2008;Nowak et al 2011). Many such neurons also express the Kv3.1 channel, and the high voltage-activated channels in such neurons may be heteromeric channels containing both Kv3.3 and Kv3.1.…”

Section: What Do Kv33 Channels Do and Where Are They?mentioning

confidence: 83%

“…; Nowak et al . ). Many such neurons also express the Kv3.1 channel, and the high voltage‐activated channels in such neurons may be heteromeric channels containing both Kv3.3 and Kv3.1.…”

Section: Introductionmentioning

confidence: 97%

Kv3.3 potassium channels and spinocerebellar ataxia

Zhang

Kaczmarek

2015

The Journal of Physiology

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The voltage-dependent potassium channel subunit Kv3.3 is expressed at high levels in cerebellar Purkinje cells, in auditory brainstem nuclei and in many other neurons capable of firing at high rates. In the cerebellum, it helps to shape the very characteristic complex spike of Purkinje cells. Kv3.3 differs from other closely related channels in that human mutations in the gene Abstract figure legend Mutations in the Kv3.3 potassium channels produce spinocerebellar ataxia type 13, a disease that results in progressive degeneration of the cerebellum.

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“…The GAD67-GFP mice have been used for the identification of GABAergic neurons in the central nervous system (CNS) including spinal dorsal horn [17, 42]. In addition, since nearly all glycinergic dorsal horn neurons in laminae I-III also contain GABA, the GFP signal is a reliable marker for the identification of inhibitory neurons in this region [46].…”

Section: Resultsmentioning

confidence: 99%

Characterization of a mouse model of headache

Huang

Ren

Qiu

et al. 2016

Pain

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Migraine and other primary headache disorders affect a large population and cause debilitating pain. Establishing animal models that display behavioral correlates of long-lasting and ongoing headache, the most common and disabling symptom of migraine, is vital for the elucidation of disease mechanisms as well as the identification of drug targets. We have developed a mouse model of headache, using dural application of capsaicin along with a mixture of inflammatory mediators (IScap) to simulate the induction of a headache episode. This elicited intermittent head-directed wiping and scratching as well as the phosphorylation of c-Jun N-terminal kinase in trigeminal ganglion neurons. Interestingly, dural application of IScap preferentially induced FOS protein expression in the excitatory but not inhibitory cervical/medullary dorsal horn neurons. The duration of IScap-induced behavior and the number of FOS-positive neurons correlated positively in individual mice; both were reduced to the control level by the pretreatment of anti-migraine drug sumatriptan. Dural application of CGRP(8–37), the calcitonin gene-related peptide (CGRP) receptor antagonist, also effectively blocked IScap-induced behavior, suggesting that the release of endogenous CGRP in dura is necessary for IScap-induced nociception. These data suggest that dural IScap-induced nocifensive behavior in mice may be mechanistically related to the ongoing headache in humans. In addition, dural application of IScap increased resting time in female mice.. Taken together, we present here the first detailed study using dural application of IScap in mice. This headache model can be applied to genetically modified mice to facilitate the research for the mechanisms and therapeutic targets for migraine headache.

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Kv3.1b and Kv3.3 channel subunit expression in murine spinal dorsal horn GABAergic interneurones

Cited by 14 publications

References 46 publications

NMDA receptor activation induces long-term potentiation of glycine synapses

NMDA receptor activation induces long-term potentiation of glycine synapses

Kv3.3 potassium channels and spinocerebellar ataxia

Characterization of a mouse model of headache

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