1,721,145 research outputs found
Metabotropic glutamate receptors as targets for novel anxiolytics
No full textAnxiety disorders are highly prevalent psychiatric illnesses posing an important social and economic burden. Their current pharmacotherapy shows short term efficacy, though nearly one third of patients do not achieve sustained remission. There is, therefore, a strong medical need for new therapeutic agents acting through novel mechanisms of action. Considerable work has focused on metabotropic glutamate (mGlu) receptors as potential targets for novel anxiolytics. Ligands acting at mGlu receptors showed promising results in preclinical studies, whereas their efficacy was dubious in clinical trials. Recent preclinical and clinical studies have opened new prospects for targeting mGlu receptors to treat anxiety disorders. This review provides an outlook on these progresses
Subpopulations of neurokinin 1 receptor-expressing neurons in the rat lateral amygdala display a differential pattern of innervation from distinct glutamatergic afferents
Full text linkAbstractSubstance P by acting on its preferred receptor neurokinin 1 (NK1) in the amygdala appears to be critically involved in the modulation of fear and anxiety. The present study was undertaken to identify neurochemically specific subpopulations of neuron expressing NK1 receptors in the lateral amygdaloid nucleus (LA), a key site for regulating these behaviors. We also analyzed the sources of glutamatergic inputs to these neurons. Immunofluorescence analysis of the co-expression of NK1 with calcium binding proteins in LA revealed that ∼35% of NK1-containing neurons co-expressed parvalbumin (PV), whereas no co-localization was detected in the basal amygdaloid nucleus. We also show that neurons expressing NK1 receptors in LA did not contain detectable levels of calcium/calmodulin kinase IIα, thus suggesting that NK1 receptors are expressed by interneurons. By using a dual immunoperoxidase/immunogold-silver procedure at the ultrastructural level, we found that in LA ∼75% of glutamatergic synapses onto NK1-expressing neurons were labeled for the vesicular glutamate transporter 1 indicating that they most likely are of cortical, hippocampal, or intrinsic origin. The remaining ∼25% were immunoreactive for the vesicular glutamate transporter 2 (VGluT2), and may then originate from subcortical areas. On the other hand, we could not detect VGluT2-containing inputs onto NK1/PV immunopositive neurons. Our data add to previous localization studies by describing an unexpected variation between LA and basal nucleus of the amygdala (BA) in the neurochemical phenotype of NK1-expressing neurons and reveal the relative source of glutamatergic inputs that may activate these neurons, which in turn regulate fear and anxiety responses
Metabotropic glutamate receptors
No full textMetabotropic glutamate receptors (mGlus) are a family of G-protein-coupled receptors activated by the neurotransmitter glutamate. Molecular cloning has revealed eight different subtypes (mGlu1-8) with distinct molecular and pharmacological properties. Multiplicity in this receptor family is further generated through alternative splicing. mGlus activate a multitude of signalling pathways important for modulating neuronal excitability, synaptic plasticity and feedback regulation of neurotransmitter release. In this review, we summarize anatomical findings (from our work and that of other laboratories) describing their distribution in the central nervous system. Recent evidence regarding the localization of these receptors in peripheral tissues will also be examined. The distinct regional, cellular and subcellular distribution of mGlus in the brain will be discussed in view of their relationship to neurotransmitter release sites and of possible functional implications. © Springer-Verlag 2006
Sequence-based imitation learning for surgical robot operations
Full text linkAim: This paper aims to advance autonomous surgical operations through imitation learning from video demonstrations. Methods: To address this objective, we propose two main contributions: (1) We introduce a new dataset of virtual kidney tumor environments to train our model on. The dataset is composed of video demonstrations of tumor removal from the kidney, executed in a virtual environment, and kinematic data of the robot tools; (2) We employed an imitation learning architecture composed of vision transformers (ViT) to handle the frames extracted from the videos and of a long short-term memory (LSTM) structure to process surgical motion sequences with a sliding window mechanism. This model processes video frames and prior poses to predict the poses for both robotic arms. A self-generating sequence approach was implemented, where each predicted pose served as the latest element in the sequence, subsequently used as input for the next prediction together with the current frame of the video. The choice of architecture and methodology was guided by the need to effectively model the sequential nature of surgical operations. Results: The model achieved promising results, exhibiting an average position error of 0.5 cm. The model was able to execute correctly 70% of the test tasks. This highlights the sequence-based approach's efficacy in capturing and predicting surgical trajectories. Conclusion: Our study supports imitation learning's viability for acquiring task execution policies in surgical robotics. The sequence-based model, combining ViT and LSTM architectures, successfully handles surgical trajectories
Metabotropic glutamate 1 receptor: Current concepts and perspectives
No full textAlmost 25 years after the first report that glutamate can activate receptors coupled to heterotrimeric G-proteins, tremendous progress has been made in the field of metabotropic glutamate receptors. Now, eight members of this family of glutamate receptors, encoded by eight different genes that share distinctive structural features have been identified. The first cloned receptor, the metabotropic glutamate (mGlu) receptor mGlu1 has probably been the most extensively studied mGlu receptor, and in many respects it represents a prototypical subtype for this family of receptors. Its biochemical, anatomical, physiological, and pharmacological characteristics have been intensely investigated. Together with subtype 5, mGlu1 receptors constitute a subgroup of receptors that couple to phospholipase C and mobilize Ca2+ from intracellular stores. Several alternatively spliced variants of mGlu1 receptors, which differ primarily in the length of their C-terminal domain and anatomical localization, have been reported. Use of a number of genetic approaches and the recent development of selective antagonists have provided a means for clarifying the role played by this receptor in a number of neuronal systems. In this article we discuss recent advancements in the pharmacology and concepts about the intracellular transduction and pathophysiological role of mGlu1 receptors and review earlier data in view of these novel findings. The impact that this new and better understanding of the specific role of these receptors may have on novel treatment strategies for a variety of neurological and psychiatric disorders is considered. Copyright © 2008 by The American Society for Pharmacology and Experimental Therapeutics
MyWelder: A collaborative system for intuitive robot-assisted welding
No full textWelding is an industrial application where automation is always increasing. The reasons behind this are twofold: on one hand the shortage of experienced welding professionals, on the other hand the gain in process quality and productivity. However, fully automated solutions, like the use of industrial robots dedicated to welding, are difficult to be exploited, especially in small and medium-sized enterprises, due to the complexity of robot programming. In this paper, we propose MyWelder, a robot-assisted welding solution for automated MIG/MAG welding. The system is intuitive and easily programmable and ensures high productivity even with small production batches. An extended experimental validation with professional welders has been carried out to evaluate the performance of the system and its usability
Energy optimization for a robust and flexible interaction control
No full textThe possibility of adapting online the way a robot interacts with the environment is becoming more and more important. In this paper we introduce the tank based admittance controller. We show that all the admittance controllers can be modeled as an energy optimization problem and then we introduce a novel admittance control strategy that allows to change online the interactive behavior while preserving a stable interaction with the environment. The effectiveness of the proposed architecture is experimentally validated
Differential expression of SAPK isoforms in the rat brain. An in situ hybridisation study in the adult rat brain and during post-natal development
No full textMAPK pathways transduce a broad variety of extracellular signals into cellular responses. Despite their pleiotropic effects and their ubiquitous distribution, surprisingly little is known about their involvement in the communication network of nerve cells. As a first step to elucidate the role of MAPK pathways in neuronal signalling, we studied the distribution of SAPK α/JNK2, SAPK β/JNK3, and SAPK γ/JNK1, three isoforms of SAPK/JNK, a stress-activated MAPK subfamily. We compared the mRNA localisation of the three main isoforms in the adult and developing rat brain using in situ hybridisation. In the adult brain, SAPK α and β were widely but heterogeneously distributed, reproducing the pattern of a probe that does not discriminate the isoforms. Differently, high labelling for the SAPK γ probe was exclusively localised in the endopiriform nucleus and medial habenula. Intermediate staining was detected in the hippocampus. During post-natal development, SAPK β showed the same localisation as in the adult. Nevertheless, the semi-quantitative analysis of optical densities showed significantly different mRNA levels. In the adult, SAPK γ signal was weak, whereas in newborn rats the labelling was intense and widely distributed. SAPK γ mRNA levels decreased during development, to reach the low signals detected in the adult. These results suggest that in the central nervous system SAPK-type MAP kinases perform significant physiological functions which are particularly relevant during post-natal development. The distinct distribution patterns of SAPK isoforms in the adult rat brain support the hypothesis that separate functions are performed by the products of the three SAPK genes
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