Possible role of calcitonin gene‐related peptide in trigeminal modulation of glomerular microcircuits of the rodent olfactory bulb

Abstract

Chemosensation in the mammalian nose comprises detection of odorants, irritants and pheromones. While the traditional view assigned one distinct sub-system to each stimulus type, recent research has produced a more complex picture. Odorants are not only detected by olfactory sensory neurons but also by the trigeminal system. Irritants, in turn, may have a distinct odor, and some pheromones are detected by the olfactory epithelium. Moreover, it is well established that irritants change odor perception and vice versa. A wealth of psychophysical evidence on olfactory-trigeminal interactions in humans contrasts with a paucity of structural insight. In particular, it is unclear whether the two systems communicate just by sharing stimuli, or whether neuronal connections mediate cross-modal signaling. One connection could exist in the olfactory bulb that performs the primary processing of olfactory signals and receives trigeminal innervation. In the present study, neuroanatomical tracing of the mouse ethmoid system illustrates how peptidergic fibers enter the glomerular layer of the olfactory bulb, where local microcircuits process and filter the afferent signal. Biochemical assays reveal release of calcitonin gene-related peptide from olfactory bulb slices and attenuation of cAMP signaling by the neuropeptide. In the non-stimulated tissue, the neuropeptide specifically inhibited the basal activity of calbindin-expressing periglomerular interneurons, but did not affect the basal activity of neurons expressing calretinin, parvalbumin, or tyrosine hydroxylase, nor the activity of astrocytes. This study represents a first step towards understanding trigeminal neuromodulation of olfactory-bulb microcircuits and provides a working hypothesis for trigeminal inhibition of olfactory signal processing. This article is protected by copyright. All rights reserved.

Photoactivation of olfactory sensory neurons does not affect action potential conduction in individual trigeminal sensory axons innervating the rodent nasal cavity

“…CGRP-positive axons are evident in the olfactory bulb and are of trigeminal origin as evidence by their absence following lesion of the ophthalmic division [63]. Ethmoid peptidergic axons presumably enter the olfactory bulb together with the olfactory tract but may also span the leptomeninges from the olfactory dura mater as observed in rat pups [22,64]. Since our recordings from the ethmoid nerve necessitated removal of the olfactory bulb, we were not able to test the possibility of trigeminal axon branching into the olfactory bulb.…”

“…Most studies have focused on the suppressive effect of trigeminal stimuli that elicit sensations of pungency on the perception of odorants. Similarly, in animal models, the impact of trigeminal activation on olfactory signaling has been examined and release of calcitonin gene-related peptide (CGRP) from trigeminal afferents can suppress excitatory signals in olfactory sensory neurons [5,22]. However, olfactory signaling can also influence signaling in trigeminal sensory neurons [23,24].…”

Linalool odor‐induced analgesia is triggered by TRPA1-independent pathway in mice

“…The exact location of the interaction between the two systems is not yet determined. But several anatomical areas such as the olfactory epithelium, the olfactory bulb, the mediodorsal thalamus, the piriform cortex, the orbitofrontal cortex and the insula cortex have been proposed as the site [5,7,11,[16][17][18].…”

“…In addition to the classical main olfactory pathway, the trigeminal nerve pathway contributes to the detection of odorous compounds in the nostril [4]. The ethmoidal nerve arising from the ophthalmic division of the trigeminal nerve projects into the nasal cavity and makes free end terminals in the epithelium [5][6][7][8]. The central projections of the ethmoidal nerve terminate on the superficial laminae of the medullary dorsal horn [9,10] with collateral branches which reach directly to the olfactory bulb [7,11].…”

Photoactivation of olfactory sensory neurons does not affect action potential conduction in individual trigeminal sensory axons innervating the rodent nasal cavity

“…Most studies have focused on the suppressive effect of trigeminal stimuli that elicit sensations of pungency, on the perception of odorants. Similarly, in animal models, the impact of trigeminal activation on olfactory signaling has been examined and release of calcitonin gene-related peptide (CGRP) from trigeminal afferents can suppress excitatory signals in olfactory sensory neurons [5,23]. However, it is also possible that olfactory signaling can influence signaling in trigeminal sensory neurons [24,25].…”