scholarly journals Single neuron serotonin receptor subtype gene expression correlates with behaviour within and across three molluscan species

2018 ◽  
Vol 285 (1885) ◽  
pp. 20180791 ◽  
Author(s):  
A. N. Tamvacakis ◽  
A. Senatore ◽  
P. S. Katz

The marine mollusc, Pleurobranchaea californica varies daily in whether it swims and this correlates with whether serotonin (5-HT) enhances the strength of synapses made by the swim central pattern generator neuron, A1/C2. Another species, Tritonia diomedea , reliably swims and does not vary in serotonergic neuromodulation. A third species, Hermissenda crassicornis , never produces this behaviour and lacks the neuromodulation. We found that expression of particular 5-HT receptor subtype (5-HTR) genes in single neurons correlates with swimming. Orthologues to seven 5-HTR genes were identified from whole-brain transcriptomes. We isolated individual A1/C2 neurons and sequenced their RNA or measured 5-HTR gene expression using absolute quantitative PCR. A1/C2 neurons isolated from Pleurobranchaea that produced a swim motor pattern just prior to isolation expressed 5-HT2a and 5-HT7 receptor genes, as did all Tritonia samples. These subtypes were absent from A1/C2 isolated from Pleurobranchaea that did not s wim on that day and from Hermissenda A1/C2 neurons. Expression of other receptors was not correlated with swimming. This suggests that these 5-HTRs may mediate the modulation of A1/C2 synaptic strength and play an important role in swimming. Furthermore, it suggests that regulation of receptor expression could underlie daily changes in behaviour as well as evolution of behaviour.

2017 ◽  
Author(s):  
A.N. Tamvacakis ◽  
A. Senatore ◽  
P.S. Katz

AbstractThe marine mollusc, Pleurobranchaea californica varies daily in whether it swims and this correlates with whether serotonin (5-HT) enhances the strength of synapses made by the swim central pattern generator neuron, C2. Another species, Tritonia diomedea, reliably swims and does not vary in serotonergic neuromodulation. A third species, Hermissenda crassicornis, never produces this behavior and lacks the neuromodulation. We found that expression of particular 5-HT receptor genes in C2 correlates with swimming. Seven 5-HT receptor subtype genes were identified from whole-brain transcriptomes. We isolated individual C2 neurons and sequenced their RNA or measured 5-HT receptor gene expression using quantitative PCR. C2 neurons isolated from Pleurobranchaea individuals that produced a swim motor pattern just prior to isolation expressed the 5-HT2a and 5-HT7 receptor genes, as did the Tritonia samples. These subtypes were absent from C2 neurons isolated from Pleurobranchaea individuals that did not swim that day and from Hermissenda C2 neurons. Expression of other receptors did not correlate with swimming. This suggests that 5-HT2a and 5-HT7 receptors mediate the modulation of C2 synaptic strength and play an important role in swimming. Furthermore, the results suggest that regulation of receptor expression might underlie daily changes in behavior as well as behavioral evolution.


2014 ◽  
Vol 281 (1796) ◽  
pp. 20141532 ◽  
Author(s):  
Cheng-Yu Li ◽  
Ryan L. Earley ◽  
Shu-Ping Huang ◽  
Yuying Hsu

Contest decisions are influenced by the outcomes of recent fights (winner–loser effects). Steroid hormones and serotonin are closely associated with aggression and therefore probably also play important roles in mediating winner–loser effects. In mangrove rivulus fish, Kryptolebias marmoratus , individuals with higher testosterone (T), 11-ketotestosterone and cortisol levels are more capable of winning, but titres of these hormones do not directly mediate winner–loser effects. In this study, we investigated the effects of winning/losing experiences on brain expression levels of the receptor genes for androgen (AR), oestrogen α/β (ER α/β ), glucocorticoid (GR) and serotonin (5-HT 1A R). The effect of contest experience on AR gene expression depended on T levels: repeated losses decreased, whereas repeated wins increased AR gene expression in individuals with low T but not in individuals with medium or high T levels. These results lend strong support for AR being involved in mediating winner–loser effects, which, in previous studies, were more detectable in individuals with lower T. Furthermore, the expression levels of ER α/β , 5-HT 1A R and GR genes were higher in individuals that initiated contests against larger opponents than in those that did not. Overall, contest experience, underlying endocrine state and hormone and serotonin receptor expression patterns interacted to modulate contest decisions jointly.


2019 ◽  
Author(s):  
Min Tae M. Park ◽  
Peter Jeon ◽  
Ali R. Khan ◽  
Kara Dempster ◽  
M. Mallar Chakravarty ◽  
...  

AbstractObjectiveThe hippocampus is considered a putative marker in schizophrenia with early volume deficits of select subfields. Certain subregions are thought to be more vulnerable due to a glutamate-driven mechanism of excitotoxicity, hypermetabolism, and then degeneration. Here, we explored whether hippocampal anomalies in first-episode psychosis (FEP) correlate with glutamate receptor density via a serotonin receptor proxy by leveraging structural neuroimaging, spectroscopy (MRS), and gene expression.MethodsHigh field 7T brain MR images were collected from 27 control, 41 FEP participants, along with 1H-MRS measures of glutamate. Automated methods were used to delineate the hippocampus and atlases of the serotonin receptor system were used to map receptor density across the hippocampus and subfields. We used gene expression data from the Allen Human Brain Atlas to test for correlations between serotonin and glutamate receptor genes.ResultsWe found reduced hippocampal volumes in FEP, replicating previous findings. Amongst the subfields, CA4-dentate gyrus showed greatest reductions. Gene expression analysis indicated 5-HTR1A and 5-HTR4 receptor subtypes as predictors of AMPA and NMDA receptor expression, respectively. Volumetric differences in the subfields correlated most strongly with 5-HT1A (R=0.64, p=4.09E-03) and 5-HT4 (R=0.54, p=0.02) densities as expected, and replicated using previously published data from two FEP studies. Measures of individual structure-receptor alignment were derived through normative modeling of hippocampal shape and correlations to receptor distributions, termed Receptor-Specific Morphometric Signatures (RSMS). Right-sided 5-HT4 RSMS was correlated with glutamate (R=0.357, p=0.048).ConclusionsWe demonstrate glutamate-driven hippocampal remodeling in FEP through a receptor-density gated mechanism, thus providing a mechanistic explanation of how redox dysregulation affects brain structure and symptomatic heterogeneity in schizophrenia.


1999 ◽  
Vol 70 (2) ◽  
pp. 282-287 ◽  
Author(s):  
Joyce L.W Yau ◽  
Tommy Olsson ◽  
June Noble ◽  
Jonathan R Seckl

2005 ◽  
Vol 18 (2) ◽  
pp. 113
Author(s):  
Myung Ha Yoon ◽  
Hong Buem Bae ◽  
Jeong Il Choi ◽  
Seok Jae Kim ◽  
Chang Mo Kim ◽  
...  

2021 ◽  
Vol 22 (10) ◽  
pp. 5285
Author(s):  
Kazuhiro Mio ◽  
Shoko Fujimura ◽  
Masaki Ishihara ◽  
Masahiro Kuramochi ◽  
Hiroshi Sekiguchi ◽  
...  

Serotonin receptors play important roles in neuronal excitation, emotion, platelet aggregation, and vasoconstriction. The serotonin receptor subtype 2A (5-HT2AR) is a Gq-coupled GPCR, which activate phospholipase C. Although the structures and functions of 5-HT2ARs have been well studied, little has been known about their real-time dynamics. In this study, we analyzed the intramolecular motion of the 5-HT2AR in living cells using the diffracted X-ray tracking (DXT) technique. The DXT is a very precise single-molecular analytical technique, which tracks diffraction spots from the gold nanocrystals labeled on the protein surface. Trajectory analysis provides insight into protein dynamics. The 5-HT2ARs were transiently expressed in HEK 293 cells, and the gold nanocrystals were attached to the N-terminal introduced FLAG-tag via anti-FLAG antibodies. The motions were recorded with a frame rate of 100 μs per frame. A lifetime filtering technique demonstrated that the unliganded receptors contain high mobility population with clockwise twisting. This rotation was, however, abolished by either a full agonist α-methylserotonin or an inverse agonist ketanserin. Mutation analysis revealed that the “ionic lock” between the DRY motif in the third transmembrane segment and a negatively charged residue of the sixth transmembrane segment is essential for the torsional motion at the N-terminus of the receptor.


2006 ◽  
Vol 190 (2) ◽  
pp. 373-384 ◽  
Author(s):  
Shannon M Gifford ◽  
Fu-Xian Yi ◽  
Ian M Bird

Uterine artery endothelial cells (UAEC) derived from pregnant (P-UAEC) and nonpregnant (NP-UAEC) ewes retain pregnancy-specific differences in cell signaling as well as vasodilator production through passage 4. In particular, when P- and NP-UAEC are stimulated with ATP over a 2.5 min recording period, they exhibit similar initial transient peaks in the intracellular free Ca2+ concentration ([Ca2+]i), but the P-UAEC show a heightened sustained phase. In order to establish whether thiswas due to an altered subclass of purinergic receptor (P2), both the dose dependencyof [Ca2+]i responses to ADP and UTP and the profile of purinergic receptor expression are determined in NP- and P-UAEC. Our findings indicate that while several isoforms of P2X and P2Y receptors are present, it is P2Y2 that is responsible for the ATP-induced initial transient peak in both cell types. We also characterized several key components of the ATP-induced Ca2+ signaling cascade, including the inositol 1,4,5-trisphosphate receptor and G-proteins, but could not confirm any pregnancy-specific variation in the protein expression that correlated with pregnancy-specific differences in prolonged Ca2+ signaling. We thus investigated whether such a difference may be inherent to the cell itself rather than specific to the purinergic receptor-signaling pathway. Using thapsigargin (Tg), we were able to demonstrate that the initial Tg-sensitive intracellular pool of Ca2+is nearly identical with the capacity in both cell types, but the P-UAEC is nonetheless capable of greater capacitative Ca2+ entry (CCE) than NP-UAEC. Furthermore, CCE induced by Tg could be dramatically inhibited by 2-aminoethoxydiphenyl borate, suggesting a role for store-operated channels in the ATP-induced [Ca2+]i response. We conclude that changes at the level of capacitative entry mechanisms rather than switching of receptor subtype or coupling to phospholipase C underlies pregnancy adaptation of UAEC at the level of Ca2+signaling.


Endocrinology ◽  
2005 ◽  
Vol 146 (11) ◽  
pp. 4878-4886 ◽  
Author(s):  
Michelle Breuiller-Fouché ◽  
Catherine Morinière ◽  
Emmanuelle Dallot ◽  
Stéphanie Oger ◽  
Régis Rebourcet ◽  
...  

Proinflammatory cytokines produced at the fetomaternal interface, such as IL-1β, have been implicated in preterm and term labor. The present study was performed to evaluate the influence of IL-1β on the endothelin (ET)/ET receptor system in human myometrial cells. We report that myometrial cells under basal conditions not only respond to but also secrete ET-1, one of the main regulators of uterine contractions. Prolonged exposure of the cells to IL-1β led to a decrease in prepro-ET-1 and ET-3 mRNA correlated with a decrease in immunoreactive ET-1 and ET-3 levels in the culture medium. Whereas ETA receptor expression at both protein and mRNA levels was not affected by IL-1β treatment, we demonstrated an unexpected predominance of the ETB receptor subtype under this inflammatory condition. Whereas the physiological function of ETB remains unclear, we confirmed that only ETA receptors mediate ET-1-induced myometrial cell contractions under basal conditions. By contrast, prolonged exposure of the cells to IL-1β abolished the contractile effect induced by ET-1. Such a regulation of IL-1β on the ET release and the balance of ETA to ETB receptors leading to a loss of ET-1-induced myometrial cell contractions suggest that complex regulatory mechanisms take place to constraint the onset of infection-induced premature contractions.


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