Properties of Primary Sensory (Lemniscal) Synapses in the Ventrobasal Thalamus and the Relay of High-Frequency Sensory Inputs

2002 ◽  
Vol 87 (2) ◽  
pp. 946-953 ◽  
Author(s):  
Manuel A. Castro-Alamancos

The main role of the thalamus is to relay sensory inputs to the neocortex. In the primary somatosensory thalamus (ventrobasal thalamus), sensory inputs deliver tactile information through the medial lemniscus tract. The transmission of sensory information through this pathway is affected by behavioral state. For instance, the relay of high-frequency somatosensory inputs through the thalamus is suppressed during anesthesia or quiescent states but allowed during behaviorally activated states. This change may be due to the effects of modulators on the efficacy of lemniscal synapses. Here I show that lemniscal synapses of adult rodents studied in vitro produce large amplitude-highly secure unitary excitatory postsynaptic potentials (EPSPs), which depress in response to repetitive stimulation at frequencies >2 Hz. Acetylcholine and norepinephrine, which are important thalamic modulators, have no effect on the efficacy of lemniscal EPSPs but reduce evoked inhibitory postsynaptic potentials and corticothalamic EPSPs. Although acetylcholine and norepinephrine do not affect lemniscal synapses, the postsynaptic depolarization they produce on thalamocortical neurons serves to warrant the relay of lemniscal inputs at high-frequency rates by bringing the depressed lemniscal EPSPs close to firing threshold. In conclusion, acetylcholine and norepinephrine released during activated states selectively enhance sensory transmission through the lemniscal pathway by depolarizing thalamocortical neurons and simultaneously depressing the other afferent pathways.

2012 ◽  
Vol 108 (3) ◽  
pp. 709-711 ◽  
Author(s):  
Yann Thibaudier ◽  
Marie-France Hurteau

Propriospinal pathways are thought to be critical for quadrupedal coordination by coupling cervical and lumbar central pattern generators (CPGs). However, the mechanisms involved in relaying information between girdles remain largely unexplored. Using an in vitro spinal cord preparation in neonatal rats, Juvin and colleagues ( Juvin et al. 2012 ) have recently shown sensory inputs from the hindlimbs have greater influence on forelimb CPGs than forelimb sensory inputs on hindlimb CPGs, in other words, a bottom-up control system. However, results from decerebrate cats suggest a top-down control system. It may be that both bottom-up and top-down control systems exist and that the dominance of one over the other is task or context dependent. As such, the role of sensory inputs in controlling quadrupedal coordination before and after injury requires further investigation.


1983 ◽  
Vol 50 (3) ◽  
pp. 658-670 ◽  
Author(s):  
A. D. McClellan

The buccal mass of the gastropod Pleurobranchaea is used during a regurgitation response that consists of a writhing phase interrupted by brief periodic bouts of a vomiting phase (17, 20). During transitions from writhing to vomiting, specific changes occur in the motor pattern (19, 20). Evidence is presented suggesting that at least some of the initiation or "command" neurons for vomiting reside in the buccal ganglia. The present paper examines the role of two candidate vomiting-initiation cells, the ventral white cells (VWC) and midganglionic cells (MC), in the buccal ganglia of isolated nervous systems. Stimulation of single VWCs activates a vomiting motor pattern, consisting in part of alternating buccal root activity. Furthermore, the VWCs fire in high-frequency bursts during episodes (i.e., bouts) of this same vomiting pattern. Mutual reexcitation between the VWCs and motor pattern generator (MPG) appears to produce the accelerated buildup and maintenance of vomiting rhythms. Brief stimulation of single MCs "triggers" bouts of a vomiting motor pattern, but the membrane potential of this cell is only modulated during this same pattern, at least in the isolated nervous system. It is proposed that in intact animals the MCs are activated by sensory inputs and briefly excite the VWC-MPG network, thereby turning on the mutual reexcitatory mechanism mentioned above and switching the output pattern. A general implication for gastropod research is that higher order neurons that activate buccal root activity cannot automatically be given the function of "feeding command neuron," as some cells clearly control other responses, such as vomiting.


2008 ◽  
Vol 294 (1) ◽  
pp. G130-G138 ◽  
Author(s):  
Klaus Bielefeldt ◽  
Brian M. Davis

Using a recently developed in vitro preparation of vagal afferent pathways, we examined the role of TRPV1 and ASIC3 on the mechano- and chemosensitive properties of gastroesophageal sensory neurons. Esophagus, stomach, and the intact vagus nerves up to the central terminations were carefully dissected from TRPV1 and ASIC3 knockout mice and wild-type controls. The organ preparation was placed in a superfusion chamber to obtain intracellular recordings from the soma of nodose neurons during luminal stimulation of esophagus and stomach. The proximal esophagus and distal stomach were separately intubated to allow perfusion and graded luminal distension. In wild-type mice, mechanosensitive neurons were activated by low distension pressures and encoded stimulus intensity over the entire range tested. Luminal acidification significantly transiently increased the resting frequency but did not alter responses to subsequent mechanical stimulation. ASIC3 and TRPV1 knockout significantly blunted responses to distension compared with wild-type controls, with deletion of TRPV1 having a more significant effect than ASIC3 deletion. Luminal acidification did not activate mechanosensory neurons in ASIC3 and TRPV1 knockout mice. Our data demonstrate a role of TRPV1 in chemo- and mechanosensation of gastroesophageal afferents. ASIC3 may contribute to acid sensation but plays a more subtle role in responses to distending stimuli. Considering the importance of acid in dyspeptic symptoms and gastroesophageal reflux, TRPV1 or ASIC3 may be an attractive target for treatment strategies in patients who do not respond to acid suppressive therapy.


Reproduction ◽  
2003 ◽  
pp. 689-699 ◽  
Author(s):  
PA Fowler ◽  
T Sorsa-Leslie ◽  
W Harris ◽  
HD Mason

When gonadotrophin-stimulated IVF methods were being developed in the 1970s and 1980s, understanding of the physiology of FSH improved. In addition to its classic actions of stimulating aromatase activity and oestradiol secretion by ovarian granulosa cells, FSH was found to stimulate the ovarian production of an uncharacterized hormone known by its specific effect of reducing pituitary responsiveness to GnRH. This hormone has been called gonadotrophin surge-attenuating factor (GnSAF), gonadotropin surge-inhibiting factor (GnSIF), various abbreviations (GnSAF/IF, GnSIF/AF) and also attenuin. Although first described in the 1980s, GnSAF has still not been convincingly characterized and no published candidate amino acid sequences conclusively relate to GnSAF bioactivity. On the basis of superovulation studies and in vitro experimentation into the roles of steroids in regulating LH, GnRH and GnRH self-priming, the concept that GnSAF has a role in the regulation of LH secretion, the timing of the LH surge and the prevention of premature luteinization developed. For at least a decade, understanding of the specific GnSAF effects of reducing pituitary sensitivity to GnRH, especially GnRH self-priming and antagonizing the stimulatory effects of oestradiol on GnRH-induced LH secretion, supported this concept. However, improved knowledge of the changes in GnSAF bioactivity in follicular fluid and serum in women requires revision of this concept. The present authors propose that the main role of GnSAF is probably the negative regulation of pulsatile LH secretion, mainly during the first half of the follicular phase, indicating a critical role in the regulation of folliculogenesis and oestradiol secretion.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Mariana Norton ◽  
Simon C Cork ◽  
Aldara Martin Alonso ◽  
Anna G Roberts ◽  
Yateen S Patel ◽  
...  

Abstract The existence of a vago-vagal entero-pancreatic pathway, where sensory information from the gut can signal via vagal afferents to the brain to mediate changes in pancreatic function, has been recognised for over a century, and investigated extensively with regards to pancreatic exocrine secretions. However, the role of such pathways in pancreatic endocrine secretions has received less attention. The secretion of insulin and glucagon in response to protein and amino acids is conserved across species. This effect is thought to promote amino acid uptake into tissues without concomitant hypoglycaemia. We found that the essential amino acid L-Phenylalanine potently stimulates glucagon secretion, even when administered directly into the gut at small doses unlikely to significantly raise systematic levels. Administration of L-Phenylalanine also increased neuronal activation in the rat and mouse dorsal vagal complex, the central nervous system region directly innervated by vagal afferents. L-Phenylalanine modulates the activity of the calcium sensing receptor (CaSR), a nutrient sensor more commonly known for its role in calcium homeostasis, but which is thought to also act as a sensor of aromatic amino acids. Interestingly, the CaSR is one of the few nutrient sensors expressed in vagal afferents and in vitro calcium imaging revealed CaSR synthetic agonists activate subpopulations of vagal afferents. The role of CaSR in vivo was investigated further by selectively knocking down the CaSR in vagal afferents. Briefly, CaSR floxed mice were bilaterally injected directly into the nodose ganglion, where the cell bodies of vagal afferents are located, with a cre expressing adeno-associated virus. CaSR knockdown did not interfere with normal food intake, nor the vagal-dependent anorectic effects of cholecystokinin, or of L-Phenylalanine. However, it did blunt protein-induced glucagon secretion, suggesting involvement of the CaSR in the vagus nerve in protein sensing and glucose homeostasis. Future studies are required to determine the importance of vagal CaSR in protein induced pancreatic endocrine secretions, and the possibility of exploiting this circuit to develop new anti-diabetic therapies.


2019 ◽  
Vol 20 (6) ◽  
pp. 1443 ◽  
Author(s):  
Marcin Magacz ◽  
Karolina Kędziora ◽  
Jacek Sapa ◽  
Wirginia Krzyściak

Lactoperoxidase (LPO) present in saliva are an important element of the nonspecific immune response involved in maintaining oral health. The main role of this enzyme is to oxidize salivary thiocyanate ions (SCN−) in the presence of hydrogen peroxide (H2O2) to products that exhibit antimicrobial activity. LPO derived from bovine milk has found an application in food, cosmetics, and medical industries due to its structural and functional similarity to the human enzyme. Oral hygiene products enriched with the LPO system constitute an alternative to the classic fluoride caries prophylaxis. This review describes the physiological role of human salivary lactoperoxidase and compares the results of clinical trials and in vitro studies of LPO alone and complex dentifrices enriched with bovine LPO. The role of reactivators and inhibitors of LPO is discussed together with the possibility of using nanoparticles to increase the stabilization and activity of this enzyme.


2021 ◽  
Vol 65 (4) ◽  
pp. 12-19
Author(s):  
Z. Kiššová ◽  
Ľ. Tkáčiková

Abstract Dendritic cells (DC) are specialized antigen presenting cells which have the unique ability to activate naive T-lymphocytes. Their role in the immune system is much more sophisticated than it seems, as they do not kill the pathogens directly, but provide a long-lasting antigen specific immune response thanks to that sufficiently bridging the innate and the adaptive immunity. In recent years, there has been a growing interest in studies of their role in immune regulation, autoimmune reactions, as well as in immune responses against pathogens and tumours. Processing and presentation capabilities of a highly specific and unique tumour antigen makes them an interesting tool for stimulating effective anti-tumour immunity. In vitro generations of DC represent a preferred model for more detailed studies of DC biology in other fields. The aim of this review was to discuss the main role of dendritic cells in the body as well as their current use as experimental models for further scientific studies.


2020 ◽  
Author(s):  
Yunuen Moreno ◽  
Charlotte Bichara ◽  
Philippe Isope ◽  
Matilde Cordero-Erausquin

It is generally assumed that the main function of the corticospinal tract (CST) is to convey motor commands to bulbar or spinal motoneurons. Yet the CST has also been shown to modulate sensory signals at their entry point in the spinal cord, through primary afferent depolarization (PAD). By sequentially investigating different routes of corticofugal pathways, we here demonstrate that motor and PAD commands in mice belong to segregated paths within the CST. PAD is carried out exclusively by the CST via a population of lumbar interneurons located in the deep dorsal horn. In contrast, the cortex conveys the motor command via a relay in the upper spinal cord or supraspinal motor centers. At lumbar level, the main role of the CST is thus the modulation of sensory inputs, which is an essential component of the selective tuning of sensory feedback, to ensure well-coordinated and skilled movement.


2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Constanze Kurschat ◽  
Arlena Metz ◽  
Susanne Kirschnek ◽  
Georg Häcker

AbstractMitochondrial apoptosis regulates survival and development of hematopoietic cells. Prominent roles of some Bcl-2-family members in this regulation have been established, for instance for pro-apoptotic Bim and anti-apoptotic Mcl-1. Additional, mostly smaller roles are known for other Bcl-2-members but it has been extremely difficult to obtain a comprehensive picture of the regulation of mitochondrial apoptosis in hematopoietic cells by Bcl-2-family proteins. We here use a system of mouse ‘conditionally immortalized’ lymphoid-primed hematopoietic progenitor (LMPP) cells that can be differentiated in vitro to pro-B cells, to analyze the importance of these proteins in cell survival. We established cells deficient in Bim, Noxa, Bim/Noxa, Bim/Puma, Bim/Bmf, Bax, Bak or Bax/Bak and use specific inhibitors of Bcl-2, Bcl-XL and Mcl-1 to assess their importance. In progenitor (LMPP) cells, we found an important role of Noxa, alone and together with Bim. Cell death induced by inhibition of Bcl-2 and Bcl-XL entirely depended on Bim and could be implemented by Bax and by Bak. Inhibition of Mcl-1 caused apoptosis that was independent of Bim but strongly depended on Noxa and was completely prevented by the absence of Bax; small amounts of anti-apoptotic proteins were co-immunoprecipitated with Bim. During differentiation to pro-B cells, substantial changes in the expression of Bcl-2-family proteins were seen, and Bcl-2, Bcl-XL and Mcl-1 were all partially in complexes with Bim. In differentiated cells, Noxa appeared to have lost all importance while the loss of Bim and Puma provided protection. The results strongly suggest that the main role of Bim in these hematopoietic cells is the neutralization of Mcl-1, identify a number of likely molecular events during the maintenance of survival and the induction of apoptosis in mouse hematopoietic progenitor cells, and provide data on the regulation of expression and importance of these proteins during differentiation along the B cell lineage.


Crystals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 644 ◽  
Author(s):  
Alexandre V. Ivachtchenko ◽  
Oleg D. Mitkin ◽  
Dmitry V. Kravchenko ◽  
Sergiy M. Kovalenko ◽  
Svitlana V. Shishkina ◽  
...  

A method for the synthesis of 4- (1H-benzo[d]imidazole-2-yl)-1-phenyl-1H-1,2,3-triazole-5-amine was developed, and the electronic and spatial structure of this molecule was studied theoretically and experimentally. The study of interaction energies between molecules by quantum-chemical calculations allows us to recognize different levels of crystal structure organization and describe the interaction types causing their formation. The classic N-H…N and C-H…N hydrogen bonds play the main role in all the studied crystals forming the primary basic structural motif. Their role is comparable with the role of the stacking interactions. The molecular docking study predicted that the studied compound may exhibit anti-hepatitis B activity, and experimental in vitro studies confirmed that it is a potent HBV inhibitor with IC50 in a low micromolar range.


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