TRPM8-Dependent Dynamic Response in a Mathematical Model of Cold Thermoreceptor

Olivares, Erick; Salgado, Simón; Maidana, Jean Paul; Herrera, Gaspar; Campos, Matías; Madrid, Rodolfo; Orio, Patricio

doi:10.1371/journal.pone.0139314

Cited by 31 publications

(44 citation statements)

References 45 publications

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“…Stochastic skipping is also known from auditory nerve fibers (e.g., refs. 60 and 72) and cold receptors (63,73,74) and relies on the right amount of intrinsic noise (75). This similarity with P units suggests that in these systems a synchrony code is also possible.…”

Section: Readout Of Electrosensory Information In the Weakly Electricmentioning

confidence: 83%

“…This similarity with P units suggests that in these systems a synchrony code is also possible. In cold receptors, however, temperature modulations change the frequency of the driving oscillation and thereby change the timescale on which synchronous spikes could be read out (63,73,74). In the auditory system, on the other hand, where auditory nerve fibers encode amplitude modulations in similar ways to P units, a synchrony code might indeed be exploited by neurons in the cochlear nucleus.…”

Section: Readout Of Electrosensory Information In the Weakly Electricmentioning

confidence: 99%

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Synchronous spikes are necessary but not sufficient for a synchrony code in populations of spiking neurons

Grewe

Kruscha

Lindner

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Synchronous activity in populations of neurons potentially encodes special stimulus features. Selective readout of either synchronous or asynchronous activity allows formation of two streams of information processing. Theoretical work predicts that such a synchrony code is a fundamental feature of populations of spiking neurons if they operate in specific noise and stimulus regimes. Here we experimentally test the theoretical predictions by quantifying and comparing neuronal response properties in tuberous and ampullary electroreceptor afferents of the weakly electric fish Apteronotus leptorhynchus. These related systems show similar levels of synchronous activity, but only in the more irregularly firing tuberous afferents a synchrony code is established, whereas in the more regularly firing ampullary afferents it is not. The mere existence of synchronous activity is thus not sufficient for a synchrony code. Single-cell features such as the irregularity of spiking and the frequency dependence of the neuron's transfer function determine whether synchronous spikes possess a distinct meaning for the encoding of time-dependent signals. Because of the strong nonlinearity of the spiking threshold, neural noise can be beneficial by improving the representation of stimuli in populations of spiking neurons (3-7). Noise reduces the precision with which spikes lock to the stimulus (1). In populations of neurons that share a common input, for example by having overlapping receptive fields, noise as well as population heterogeneity has the advantage to decorrelate the responses (8, 9). That is, only those stimulus features that drive the population strongest could synchronize the response across neurons and thereby signal the presence of a particularly important stimulus.The role of synchronous activity in the cortex is widely discussed (6, 10-12), e.g., as a possible solution for the binding problem (for review see, e.g., refs. 13 and 14), as a separate information channel to relay visual information from thalamus to visual cortex (15), as a mechanism for gain control in visual cortex (16), or as a code for odor categories in zebrafish olfactory bulb (17).A synchrony code requires that asynchronously firing populations are synchronized or, vice versa, synchronization is escaped under certain conditions or by specific stimuli. In weakly electric fish, changes in the level of synchronization are considered an important cue for the detection of communication signals on the level of the receptor afferents (18-21) and subsequent processing in hind-and midbrain neurons (22,23). Middleton et al. (24) demonstrated that reading out population activity of electrosensory neurons with either integrators or coincidence detectors results in two distinct representations of sensory stimuli. Integrators encode low stimulus frequencies, approximately matching frequencies characteristic of prey detection and navigation. Coincidence detectors discard low-frequency information and encode predominantly higher frequencies matching the ones of c...

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Section: Readout Of Electrosensory Information In the Weakly Electricmentioning

confidence: 83%

Section: Readout Of Electrosensory Information In the Weakly Electricmentioning

confidence: 99%

Synchronous spikes are necessary but not sufficient for a synchrony code in populations of spiking neurons

Grewe

Kruscha

Lindner

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Furthermore, TRPM8 likely contributes to the ongoing activity of corneal cold thermoreceptors (Parra et al, ). Together, these findings suggest a high expression of TRPM8 in the strongly fluorescent, beaded axons; their predominately complex endings are possibly a biophysical reason for their characteristic spontaneous firing, low threshold and vigorous response to cooling typical of HB‐LT cold thermoreceptors (Carr et al, ; González‐González et al, ; Madrid et al, ; Olivares et al, ; Parra et al, ; Teichert et al, ).…”

Section: Discussionmentioning

confidence: 97%

Morphological and functional changes in TRPM8‐expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice

Alcalde

Íñigo-Portugués

González-González

et al. 2018

J of Comparative Neurology

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Morphological and functional alterations of peripheral somatosensory neurons during the aging process lead to a decline of somatosensory perception. Here, we analyze the changes occurring with aging in trigeminal ganglion (TG), TRPM8-expressing cold thermoreceptor neurons innervating the mouse cornea, which participate in the regulation of basal tearing and blinking and have been implicated in the pathogenesis of dry eye disease (DED). TG cell bodies and axonal branches were examined in a mouse line (TRPM8 -EYFP) expressing a fluorescent reporter. In 3 months old animals, about 50% of TG cold thermoreceptor neurons were intensely fluorescent, likely providing strongly fluorescent axons and complex corneal nerve terminals with ongoing activity at 34°C and low-threshold, robust responses to cooling. The remaining TRPM8 corneal axons were weakly fluorescent with nonbeaded axons, sparsely ramified nerve terminals, and exhibited a low-firing rate at 34°C, responding moderately to cooling pulses as do weakly fluorescent TG neurons. In aged (24 months) mice, the number of weakly fluorescent TG neurons was strikingly high while the morphology of TRPM8 corneal axons changed drastically; 89% were weakly fluorescent, unbranched, and often ending in the basal epithelium. Functionally, 72.5% of aged cold terminals responded as those of young animals, but 27.5% exhibited very low-background activity and abnormal responsiveness to cooling pulses. These morpho-functional changes develop in parallel with an enhancement of tear's basal flow and osmolarity, suggesting that the aberrant sensory inflow to the brain from impaired peripheral cold thermoreceptors contributes to age-induced abnormal tearing and to the high incidence of DED in elderly people.

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“…The activity of HB-LT cold thermoreceptors is also inhibited by hypo-osmotic solutions [101]. This finding suggests that under basal conditions tear film osmolarity provides a stimulus to the cold thermoreceptors that contributes to maintaining their ongoing nerve activity [67,105]. …”

Section: Neurobiological Features In Normal/non Dry Eye Diseasementioning

confidence: 99%

TFOS DEWS II pain and sensation report

et al. 2017

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Pain associated to mechanical and chemical irritation of the eye surface is mediated by trigeminal ganglia mechano- and polymodal nociceptor neurons while cold thermoreceptors detect wetness and reflexly maintain basal tear production and blinking rate. These neurons project into two regions of the trigeminal brain stem nuclear complex: ViVc, activated by changes in the moisture of the ocular surface and VcC1, mediating sensory-discriminative aspects of ocular pain and reflex blinking. ViVc ocular neurons project to brain regions that control lacrimation and spontaneous blinking and to the sensory thalamus. Secretion of the main lacrimal gland is regulated dominantly by autonomic parasympathetic nerves, reflexly activated by eye surface sensory nerves. These also evoke goblet cell secretion through unidentified efferent fibers. Neural pathways involved in the regulation of Meibonian gland secretion or mucins release have not been identified. In dry eye disease, reduced tear secretion leads to inflammation and peripheral nerve damage. Inflammation causes sensitization of polymodal and mechano-nociceptor nerve endings and an abnormal increase in cold thermoreceptor activity, altogether evoking dryness sensations and pain. Long-term inflammation and nerve injury alter gene expression of ion channels and receptors at terminals and cell bodies of trigeminal ganglion and brainstem neurons, changing their excitability, connectivity and impulse firing. Perpetuation of molecular, structural and functional disturbances in ocular sensory pathways ultimately leads to dysestesias and neuropathic pain referred to the eye surface. Pain can be assessed with a variety of questionaires while the status of corneal nerves is evaluated with esthesiometry and with in vivo confocal microscopy.

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TRPM8-Dependent Dynamic Response in a Mathematical Model of Cold Thermoreceptor

Cited by 31 publications

References 45 publications

Synchronous spikes are necessary but not sufficient for a synchrony code in populations of spiking neurons

Synchronous spikes are necessary but not sufficient for a synchrony code in populations of spiking neurons

Morphological and functional changes in TRPM8‐expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice

TFOS DEWS II pain and sensation report

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