Physiological temperatures drive glutamate release onto trigeminal superficial dorsal horn neurons

Largent-Milnes, Tally M.; Hegarty, Deborah M.; Aicher, Sue A.; Andresen, Michael

doi:10.1152/jn.00912.2013

Cited by 12 publications

(16 citation statements)

References 55 publications

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“…The present study supports the notion that while TRPV1 channels are present in CTb-labeled corneal neuron cell bodies, and play a prominent role in the peripheral transduction of noxious heat and capsaicin stimulation (Caterina et al, 1997; Caterina et al, 2000; Patapoutian et al, 2009), they may be playing a different role centrally (Kim et al, 2014; Largent-Milnes et al, 2014; Patapoutian et al, 2009; Patwardhan et al, 2009). Unlike our previous study of vesicular glutamate transporters and neuropeptides in corneal afferents (Hegarty et al, 2010), we did not find substantial expression of TRP channels in CTb-ir corneal afferents, nor any topographical differences between caudal and rostral Vc for any of the TRP channels in the present study.…”

Section: Discussionsupporting

confidence: 88%

“…While TRPV1 channels located at the periphery are known to transduce capsaicin stimulation, it is unclear what role TRPV1 channels on the central afferent terminals may play (Kim et al, 2014; Largent-Milnes et al, 2014; Patapoutian et al, 2009; Patwardhan et al, 2009). It is often presumed that primary afferent neurons that contain TRPV1 at peripheral sites also contain the same transducer at central sites.…”

Section: Introductionmentioning

confidence: 99%

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Capsaicin-responsive corneal afferents do not contain TRPV1 at their central terminals in trigeminal nucleus caudalis in rats

Hegarty¹,

Hermes²,

Largent-Milnes³

et al. 2014

Journal of Chemical Neuroanatomy

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We examined the substrates for ocular nociception in adult male Sprague-Dawley rats. Capsaicin application to the ocular surface in awake rats evoked nocifensive responses and suppressed spontaneous grooming responses. Thus, peripheral capsaicin was able to activate the central pathways encoding ocular nociception. Our capsaicin stimulus evoked c-Fos expression in a select population of neurons within rostral trigeminal nucleus caudalis in anesthetized rats. These activated neurons also received direct contacts from corneal afferent fibers traced with cholera toxin B from the corneal surface. However, the central terminals of the corneal afferents that contacted capsaicin-activated trigeminal neurons did not contain TRPV1. To determine if TRPV1 expression had been altered by capsaicin stimulation, we examined TRPV1 content of corneal afferents in animals that did not receive capsaicin stimulation. These studies confirmed that while TRPV1 was present in 30% of CTb-labeled corneal afferent neurons within the trigeminal ganglion, TRPV1 was only detected in 2% of the central terminals of these corneal afferents within the trigeminal nucleus caudalis. Other TRP channels were also present in low proportions of central corneal afferent terminals in unstimulated animals (TRPM8, 2%; TRPA1, 10%). These findings indicate that a pathway from the cornea to rostral trigeminal nucleus caudalis is involved in corneal nociceptive transmission, but that central TRP channel expression is unrelated to the type of stimulus transduced by the peripheral nociceptive endings.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Capsaicin-responsive corneal afferents do not contain TRPV1 at their central terminals in trigeminal nucleus caudalis in rats

Hegarty¹,

Hermes²,

Largent-Milnes³

et al. 2014

Journal of Chemical Neuroanatomy

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“…In the relatively protected locales of these interoreceptors, the role of TRPV1 in these central terminals is unlikely to be nociception. Our studies show that normal physiological temperatures (near 37°C) drive TRPV1 activation to cause spontaneous release of glutamate from cranial afferent terminals (Andresen et al , 2012; Largent-Milnes et al , 2014; Shoudai et al , 2010). This action-potential autonomous TRPV1 activity and glutamate release may help to maintain synapse integrity in normal conditions of silent vagal afferents (Andresen et al , 2012).…”

Section: Discussionmentioning

confidence: 73%

Localization of TRPV1 and P2X3 in unmyelinated and myelinated vagal afferents in the rat

Hermes

Andresen

Aicher

2016

Journal of Chemical Neuroanatomy

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The vagus nerve is dominated by afferent fibers that convey sensory information from the viscera to the brain. Most vagal afferents are unmyelinated, slow-conducting C-fibers, while a smaller portion are myelinated, fast-conducting A-fibers. Vagal afferents terminate in the nucleus tractus solitarius (NTS) in the dorsal brainstem and regulate autonomic and respiratory reflexes, as well as ascending pathways throughout the brain. Vagal afferents form glutamatergic excitatory synapses with postsynaptic NTS neurons that are modulated by a variety of channels. The organization of vagal afferents with regard to fiber type and channels is not well understood. In the present study, we used tract tracing methods to identify distinct populations of vagal afferents to determine if key channels are selectively localized to specific groups of afferent fibers. Vagal afferents were labeled with isolectin B4 (IB4) or cholera toxin B (CTb) to detect unmyelinated and myelinated afferents, respectively. We find that TRPV1 channels are preferentially found in unmyelinated vagal afferents identified with IB4, with almost half of all IB4 fibers showing co-localization with TRPV1. These results agree with prior electrophysiological findings. In contrast, we found that the ATP-sensitive channel P2X3 is found in a subset of both myelinated and unmyelinated vagal afferent fibers. Specifically, 18% of IB4 and 23% of CTb afferents contained P2X3. The majority of CTb-ir vagal afferents contained neither channel. Since neither channel was found in all vagal afferents, there are likely further degrees of heterogeneity in the modulation of vagal afferent sensory input to the NTS beyond fiber type.

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“…While the canonical threshold for gating TRPV1 is ∼43°C in peripheral somatic afferents, physiological temperatures near 37°C may be more relevant at central synapses [ 7 ]. At brainstem central primary synapses, normal physiological temperatures activate TRPV1 and increases spontaneous glutamate release [ 7 , 8 , 10 ]. Consequently, small fluctuations in temperature alter the frequency of spontaneous glutamate release at TRPV1 expressing synapses.…”

Section: Introductionmentioning

confidence: 99%

Temperature Differentially Facilitates Spontaneous but Not Evoked Glutamate Release from Cranial Visceral Primary Afferents

et al. 2015

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Temperature is fundamentally important to all biological functions including synaptic glutamate release. Vagal afferents from the solitary tract (ST) synapse on second order neurons in the nucleus of the solitary tract, and glutamate release at this first central synapse controls autonomic reflex function. Expression of the temperature-sensitive Transient Receptor Potential Vanilloid Type 1 receptor separates ST afferents into C-fibers (TRPV1+) and A-fibers (TRPV1-). Action potential-evoked glutamate release is similar between C- and A-fiber afferents, but TRPV1 expression facilitates a second form of synaptic glutamate release in C-fibers by promoting substantially more spontaneous glutamate release. The influence of temperature on different forms of glutamate release is not well understood. Here we tested how temperature impacts the generation of evoked and spontaneous release of glutamate and its relation to TRPV1 expression. In horizontal brainstem slices of rats, activation of ST primary afferents generated synchronous evoked glutamate release (ST-eEPSCs) at constant latency whose amplitude reflects the probability of evoked glutamate release. The frequency of spontaneous EPSCs in these same neurons measured the probability of spontaneous glutamate release. We measured both forms of glutamate from each neuron during ramp changes in bath temperature of 4–5°C. Spontaneous glutamate release from TRPV1+ closely tracked with these thermal changes indicating changes in the probability of spontaneous glutamate release. In the same neurons, temperature changed axon conduction registered as latency shifts but ST-eEPSC amplitudes were constant and independent of TRPV1 expression. These data indicate that TRPV1-operated glutamate release is independent of action potential-evoked glutamate release in the same neurons. Together, these support the hypothesis that evoked and spontaneous glutamate release originate from two pools of vesicles that are independently modulated and are distinct processes.

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Physiological temperatures drive glutamate release onto trigeminal superficial dorsal horn neurons

Cited by 12 publications

References 55 publications

Capsaicin-responsive corneal afferents do not contain TRPV1 at their central terminals in trigeminal nucleus caudalis in rats

Capsaicin-responsive corneal afferents do not contain TRPV1 at their central terminals in trigeminal nucleus caudalis in rats

Localization of TRPV1 and P2X3 in unmyelinated and myelinated vagal afferents in the rat

Temperature Differentially Facilitates Spontaneous but Not Evoked Glutamate Release from Cranial Visceral Primary Afferents

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