Oral thermosensing by murine trigeminal neurons: modulation by capsaicin, menthol and mustard oil.

KEY POINTS: Orosensory thermal trigeminal afferent neurons respond to cool, warm, and nociceptive hot temperatures with the majority activated in the cool range. Many of these thermosensitive trigeminal orosensory afferent neurons also respond to capsaicin, menthol, and/or mustard oil (allyl isothiocyanate) at concentrations found in foods and spices. There is significant but incomplete overlap between afferent trigeminal neurons that respond to oral thermal stimulation and to the above chemesthetic compounds. Capsaicin sensitizes warm trigeminal thermoreceptors and orosensory nociceptors; menthol attenuates cool thermoresponses. ABSTRACT: When consumed with foods, mint, mustard, and chili peppers generate pronounced oral thermosensations. Here we recorded responses in mouse trigeminal ganglion neurons to investigate interactions between thermal sensing and the active ingredients of these plants - menthol, allyl isothiocyanate (AITC), and capsaicin, respectively - at concentrations found in foods and commercial hygiene products. We carried out in vivo confocal calcium imaging of trigeminal ganglia in which neurons express GCaMP3 or GCAMP6s and recorded their responses to oral stimulation with thermal and the above chemesthetic stimuli. In the V3 (oral sensory) region of the ganglion, thermoreceptive neurons accounted for ∼10% of imaged neurons. We categorized them into three distinct classes: cool-responsive and warm-responsive thermosensors, and nociceptors (responsive only to temperatures ≥43-45 °C). Menthol, AITC, and capsaicin also elicited robust calcium responses that differed markedly in their latencies and durations. Most of the neurons that responded to these chemesthetic stimuli were also thermosensitive. Capsaicin and AITC increased the numbers of warm-responding neurons and shifted the nociceptor threshold to lower temperatures. Menthol attenuated the responses in all classes of thermoreceptors. Our data show that while individual neurons may respond to a narrow temperature range (or even bimodally), taken collectively, the population is able to report on graded changes of temperature. Our findings also substantiate an explanation for the thermal sensations experienced when one consumes pungent spices or mint.

Quantitative estimation of the nonstationary behavior of neural spontaneous activity.

The "stationarity time" (ST) of neuronal spontaneous activity signals of rat embryonic cortical cells, measured by means of a planar Multielectrode Array (MEA), was estimated based on the "Detrended Fluctuation Analysis" (DFA). The ST is defined as the mean time interval during which the signal under analysis keeps its statistical characteristics constant. An upgrade on the DFA method is proposed, leading to a more accurate procedure. Strong statistical correlation between the ST, estimated from the Absolute Amplitude of Neural Spontaneous Activity (AANSA) signals and the Mean Interburst Interval (MIB), calculated by classical spike sorting methods applied to the interspike interval time series, was obtained. In consequence, the MIB may be estimated by means of the ST, which further includes relevant biological information arising from basal activity. The results point out that the average ST of MEA signals lies between 2-3 seconds. Furthermore, it was shown that a neural culture presents signals that lead to different statistical behaviors, depending on the relative geometric position of each electrode and the cells. Such behaviors may disclose physiological phenomena, which are possibly associated with different adaptation/facilitation mechanisms.