scholarly journals Genetic Deletion of TrpV1 and TrpA1 Does Not Alter Avoidance of or Patterns of Brainstem Activation to Citric Acid in Mice

2020 ◽  
Vol 45 (7) ◽  
pp. 573-579
Author(s):  
Tian Yu ◽  
Courtney E Wilson ◽  
Jennifer M Stratford ◽  
Thomas E Finger

Abstract Exposure of the oral cavity to acidic solutions evokes not only a sensation of sour, but also of sharp or tangy. Acidic substances potentially stimulate both taste buds and acid-sensitive mucosal free nerve endings. Mice lacking taste function (P2X2/P2X3 double-KO mice) refuse acidic solutions similar to wildtype (WT) mice and intraoral infusion of acidic solutions in these KO animals evokes substantial c-Fos activity within orosensory trigeminal nuclei as well as of the nucleus of the solitary tract (nTS) (Stratford, Thompson, et al. 2017). This residual acid-evoked, non-taste activity includes areas that receive inputs from trigeminal and glossopharyngeal peptidergic (CGRP-containing) nerve fibers that express TrpA1 and TrpV1 both of which are activated by low pH. We compared avoidance responses in WT and TrpA1/V1 double-KO (TRPA1/V1Dbl−/−) mice in brief-access behavioral assay (lickometer) to 1, 3, 10, and 30 mM citric acid, along with 100 µM SC45647 and H2O. Both WT and TRPA1/V1Dbl−/− show similar avoidance, including to higher concentrations of citric acid (10 and 30 mM; pH 2.62 and pH 2.36, respectively), indicating that neither TrpA1 nor TrpV1 is necessary for the acid-avoidance behavior in animals with an intact taste system. Similarly, induction of c-Fos in the nTS and dorsomedial spinal trigeminal nucleus was similar in the WT and TRPA1/V1Dbl−/− animals. Taken together these results suggest non-TrpV1 and non-TrpA1 receptors underlie the residual responses to acids in mice lacking taste function.

2019 ◽  
Author(s):  
Tian Yu ◽  
Courtney E. Wilson ◽  
Jennifer M. Stratford ◽  
Thomas E Finger

ABSTRACTExposure of the oral cavity to acidic solutions evokes not only a sensation of sour, but also of sharp or tangy. Acidic substances potentially stimulate both taste buds and acid-sensitive mucosal free nerve endings. Mice lacking taste function (P2X2/P2X3 double-KO mice) refuse acidic solutions similarly to wildtype mice and intraoral infusion of acidic solutions in these KO animals evokes substantial c-Fos activity within orosensory trigeminal nuclei as well as of the nucleus of the solitary tract (nTS) (Stratford et. al 2017). This residual acid-evoked, non-taste activity includes areas that receive inputs from trigeminal and glossopharyngeal peptidergic (CGRP-containing) nerve fibers that express TrpA1 and TrpV1 both of which are activated by low pH. We compared avoidance responses in wildtype (WT) and TrpA1/V1 double KO (TRPA1/V1Db1-/-) mice in brief-access behavioral assay (lickometer) to 1, 3, 10, 30 mM citric acid, along with 100 μM SC45647 and H2O. Both WT and TRPA1/V1Db1-/- show similar avoidance, including to higher concentrations of citric acid (10 and 30 mM; pH 2.62 and pH 2.36 respectively), indicating that neither TrpA1 nor TrpV1 is necessary for the acid avoidance behavior in animals with an intact taste system. Similarly, induction of c-Fos in the nTS and dorsomedial spinal trigeminal nucleus was similar in the WT and TRPA1/V1Db1-/-animals. Taken together these results suggest non-TrpV1 and non-TrpA1 receptors underlie the residual responses to acids in mice lacking taste function.


Cephalalgia ◽  
2019 ◽  
Vol 39 (7) ◽  
pp. 892-899 ◽  
Author(s):  
Fleur Lerebours ◽  
Kader Boulanouar ◽  
Michèle Barège ◽  
Marie Denuelle ◽  
Fabrice Bonneville ◽  
...  

Objective To investigate the functional connectivity of the hypothalamus in chronic migraine compared to interictal episodic migraine in order to improve our understanding of migraine chronification. Methods Using task-free fMRI and ROI-to-ROI analysis, we compared anterior hypothalamus intrinsic connectivity with the spinal trigeminal nucleus in patients with chronic migraine (n = 25) to age- and sex-matched patients with episodic migraine in the interictal phase (n = 22). We also conducted a seed-to-voxel analysis with anterior hypothalamus as a seed. Results All patients with chronic migraine had medication overuse. We found a significant connectivity (T = 2.08, p = 0.024) between anterior hypothalamus and spinal trigeminal nucleus in the chronic group, whereas these two regions were not connected in the episodic group. The strength of connectivity was not correlated with pain intensity (rho: 0.09, p = 0.655). In the seed-to-voxel analysis, three regions were more connected with the anterior hypothalamus in the chronic group: The spinal trigeminal nuclei (MNI coordinate x = 2, y = −44, z = −62), the right dorsal anterior insula (MNI coordinate x = 10, y = 10, z = 18), and the right caudate (MNI coordinate x = 12, y = 28, z = 6). However, these correlations were no longer significant after whole brain FWE correction. Conclusion An increased functional connectivity between the anterior hypothalamus and the spinal trigeminal nucleus, as previously reported in preictal episodic migraine, was demonstrated in chronic migraine with medication overuse. This finding confirms a major role of the anterior hypothalamus in migraine and suggests that chronic migraineurs are locked in the preictal phase.


2021 ◽  
Vol 15 ◽  
Author(s):  
Isabel M. García-Guillén ◽  
Margaret Martínez-de-la-Torre ◽  
Luis Puelles ◽  
Pilar Aroca ◽  
Faustino Marín

The trigeminal column is a hindbrain structure formed by second order sensory neurons that receive afferences from trigeminal primary (ganglionic) nerve fibers. Classical studies subdivide it into the principal sensory trigeminal nucleus located next to the pontine nerve root, and the spinal trigeminal nucleus which in turn consists of oral, interpolar and caudal subnuclei. On the other hand, according to the prosomeric model, this column would be subdivided into segmental units derived from respective rhombomeres. Experimental studies have mapped the principal sensory trigeminal nucleus to pontine rhombomeres (r) r2-r3 in the mouse. The spinal trigeminal nucleus emerges as a plurisegmental formation covering several rhombomeres (r4 to r11 in mice) across pontine, retropontine and medullary hindbrain regions. In the present work we reexamined the issue of rhombomeric vs. classical subdivisions of this column. To this end, we analyzed its subdivisions in an AZIN2-lacZ transgenic mouse, known as a reference model for hindbrain topography, together with transgenic reporter lines for trigeminal fibers. We screened as well for genes differentially expressed along the axial dimension of this structure in the adult and juvenile mouse brain. This analysis yielded genes from multiple functional families that display transverse domains fitting the mentioned rhombomeric map. The spinal trigeminal nucleus thus represents a plurisegmental structure with a series of distinct neuromeric units having unique combinatorial molecular profiles.


Neuroscience ◽  
1994 ◽  
Vol 61 (3) ◽  
pp. 587-595 ◽  
Author(s):  
M. Takemura ◽  
S. Wakisaka ◽  
A. Yoshida ◽  
Y. Nagase ◽  
Y.C. Bae ◽  
...  

1995 ◽  
Vol 269 (3) ◽  
pp. R647-R661 ◽  
Author(s):  
K. Nakamura ◽  
R. Norgren

The activity of single taste neurons was recorded from the nucleus of the solitary tract before (n = 41) and after (n = 58) awake, behaving rats were switched to a sodium-free diet. During sodium deprivation, the spontaneous activity of the neurons increased (142%), but responses to water and sapid stimuli decreased. For all neurons in the sample, the mean response to water decreased to 72% of its predeprivation level, NaCl dropped to 53%, sucrose to 41%, citric acid to 68%, and quinine HCl to 84%. Despite the drop in magnitude, the response profiles of the taste neurons were not changed by the dietary condition. In the Na-replete state, 61% of the activity elicited by NaCl occurred in NaCl-best cells and 33% in sucrose-best neurons. In the depleted state, these values were 60 and 26%, respectively. Nevertheless, at the highest concentrations tested, deprivation did alter the relative responsiveness of the gustatory neurons to sucrose and NaCl in specific categories of neurons. Compared with acute preparations, dietary sodium deprivation in awake, behaving rats produced a more general reduction in the gustatory responses of neurons in the nucleus of the solitary tract. The largest reductions in elicited activity occurred for the "best stimulus" of a particular neuron, thus leading to smaller differences in response magnitude across stimuli, particularly at the highest concentrations tested.


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