167 research outputs found
Using Knockout and Transgenic Mice to Study Neurophysiology and Behavior
No full textPicciotto, Marina R., and Kevin Wickman. Using Knockout and Transgenic Mice to Study Neurophysiology and Behavior. Physiol. Rev. 78: 1131–1163, 1998. — Reverse genetics, in which detailed knowledge of a gene of interest permits in vivo modification of its expression or function, provides a powerful method for examining the physiological relevance of any protein. Transgenic and knockout mouse models are particularly useful for studies of complex neurobiological problems. The primary aims of this review are to familiarize the nonspecialist with the techniques and limitations of mouse mutagenesis, to describe new technologies that may overcome these limitations, and to illustrate, using representative examples from the literature, some of the ways in which genetically altered mice have been used to analyze central nervous system function. The goal is to provide the information necessary to evaluate critically studies in which mutant mice have been used to study neurobiological problems.</jats:p
Serotonin 2C Receptor Activates a Distinct Population of Arcuate Pro-opiomelanocortin Neurons via TRPC Channels
No full textSummarySerotonin 2C receptors (5-HT2CRs) expressed by pro-opiomelanocortin (POMC) neurons of hypothalamic arcuate nucleus regulate food intake, energy homeostasis and glucose metabolism. However, the cellular mechanisms underlying the effects of 5-HT to regulate POMC neuronal activity via 5-HT2CRs have not yet been identified. In the present study, we found the putative transient receptor potential C (TRPC) channels mediate the activation of a subpopulation of POMC neurons by mCPP (a 5-HT2CR agonist). Interestingly, mCPP-activated POMC neurons were found to be a distinct population from those activated by leptin. Together, our data suggest that 5-HT2CR and leptin receptors are expressed by distinct subpopulations of arcuate POMC neurons and that both 5-HT and leptin exert their actions in POMC neurons via TRPC channels.Video Abstrac
GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice.
No full textIt is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated that optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake and/or energy expenditure (EE). However, little is known about intrinsic molecules regulating NPY/AgRP neuronal excitability to affect long-term metabolic function. Here, we found that the G protein-gated inwardly rectifying K+ (GIRK) channels are key to stabilize NPY/AgRP neurons and that NPY/AgRP neuron-selective deletion of the GIRK2 subunit results in a persistently increased excitability of the NPY/AgRP neurons. Interestingly, increased body weight and adiposity observed in the NPY/AgRP neuron-selective GIRK2 knockout mice were due to decreased sympathetic activity and EE, while food intake remained unchanged. The conditional knockout mice also showed compromised adaptation to coldness. In summary, our study identified GIRK2 as a key determinant of NPY/AgRP neuronal excitability and driver of EE in physiological and stress conditions
The Communication Strategies and Customer's Requirements Definition at the Early Design Stages: An Empirical Study on Italian Luxury Automotive Brands
No full textAbstractAt the early stages of the product development, it is important to set up customer's requirements and translate these into the technical specifications with the highest level of precision since the changes in the late design phases have extremely high cost. These requirements are directly dependent on the correct and complete definition of perceived quality attributes. Such attention to the details is vital for the luxury car manufacturers since they are seeking to fulfill customer requirements with the high level of personalization. This research based on the perceived quality framework and presents findings from the empirical study of leading Italian luxury vehicle manufacturers. This research contributes to the existing debate regarding the correct definition of the customer's requirements and communication strategies. Moreover, it highlights possible ways to reduce information asymmetry between car manufacturers and customers
Clark Memorandum: Spring 2017
No full textA Graduate Program of Real Consequence (Kevin J Worthen) Promoting Religious Freedom in a Secular Age (Elder Lance B. Wickman) Religious Liberty Versus Secularity (Matthew S. Holland) Audacious Faith (Brett G. Scharffs)https://digitalcommons.law.byu.edu/clarkmemorandum/1060/thumbnail.jp
GPCR-dependent biasing of GIRK channel signaling dynamics by RGS6 in mouse sinoatrial nodal cells
No full textHow G protein-coupled receptors (GPCRs) evoke specific biological outcomes while utilizing a limited array of G proteins and effectors is poorly understood, particularly in native cell systems. Here, we examined signaling evoked by muscarinic (M2R) and adenosine (A1R) receptor activation in the mouse sinoatrial node (SAN), the cardiac pacemaker. M2R and A1R activate a shared pool of cardiac G protein-gated inwardly rectifying K+ (GIRK) channels in SAN cells from adult mice, but A1R-GIRK responses are smaller and slower than M2R-GIRK responses. Recordings from mice lacking Regulator of G protein Signaling 6 (RGS6) revealed that RGS6 exerts a GPCRdependent influence on GIRK-dependent signaling in SAN cells, suppressing M2R-GIRK coupling efficiency and kinetics and A1R-GIRK signaling amplitude. Fast kinetic bioluminescence resonance energy transfer assays in transfected HEK cells showed that RGS6 prefers Gαoover Gαi as a substrate for its catalytic activity and that M2R signals preferentially via Gαo, while A1R does not discriminate between inhibitory G protein isoforms. The impact of atrial/SAN-selective ablation of Gαoor Gai2 was consistent with these findings. Gai2ablation hadminimal impact onM2R-GIRK and A1R-GIRK signaling in SAN cells. In contrast, Gαoablation decreased the amplitude and slowed the kinetics of M2R-GIRK responses, while enhancing the sensitivity and prolonging the deactivation rate of A1R-GIRK signaling. Collectively, our data show that differences in GPCR-G protein coupling preferences, and the Gαosubstrate preference of RGS6, shape A1R- and M2R-GIRK signaling dynamics in mouse SAN cells.Fil: Anderson, Allison. University of Minnesota; Estados UnidosFil: Masuho, Ikuo. The Scripps Research Institute; Estados UnidosFil: Marron Fernandez de Velasco, Ezequiel. University of Minnesota; Estados UnidosFil: Nakano, Atsushi. University of California at Los Angeles; Estados UnidosFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Martemyanov, Kirill A.. The Scripps Research Institute; Estados UnidosFil: Wickman, Kevin. University of Minnesota; Estados Unido
Skating in a life context: examining the significance of aesthetic experience in sport using practical epistemology analysis
No full textThe purpose of this article is to suggest and illustrate a methodological approach for studies of learning in physical education (PE) and sport pedagogy in order to investigate and clarify the relation between how people learn and the settings or context in which they learn. Drawing on the work of John Dewey, the later works of Ludwig Wittgenstein and socio-cultural approaches, a practical epistemology analysis (PEA) with a focus on aesthetic judgements is suggested as a way of developing a valuable approach for investigating situated learning. The approach is illustrated by an analysis of a biographical story written by the English author Jenny Diski. As can be seen from the illustration, the significance of aesthetic experience for learning is visible when an author tells us about skating as a child. By using PEA to examine aesthetic experience-operationalised through the aesthetic judgements the author includes in the story-we can shed light on the relation between the skater and the situation in which skating takes place. The fact that aesthetic judgements are used by the author normatively to decide what is to be included and excluded in skating, and also that aesthetic judgements are used to make relations between the skater and her life as a whole, facilitates an exploration of the relation between the sports learner and the life situation in which learning is situated.</p
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No full textIn the hippocampus, the inhibitory neurotransmitter GABA shapes the activity of the output pyramidal neurons and plays important role in cognition. Most of its inhibitory effects are mediated by signaling from GABAB receptor to the G protein-gated Inwardly-rectifying K+ (GIRK) channels. Here, we show that RGS7, in cooperation with its binding partner R7BP, regulates GABABR-GIRK signaling in hippocampal pyramidal neurons. Deletion of RGS7 in mice dramatically sensitizes GIRK responses to GABAB receptor stimulation and markedly slows channel deactivation kinetics. Enhanced activity of this signaling pathway leads to decreased neuronal excitability and selective disruption of inhibitory forms of synaptic plasticity. As a result, mice lacking RGS7 exhibit deficits in learning and memory. We further report that RGS7 is selectively modulated by its membrane anchoring subunit R7BP, which sets the dynamic range of GIRK responses. Together, these results demonstrate a novel role of RGS7 in hippocampal synaptic plasticity and memory formation. DOI: http://dx.doi.org/10.7554/eLife.02053.001
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