ABSTRACT
Confirming the direct link between neural circuit activity and animal behavior has been a principal aim of neuroscience. The genetically encoded calcium indicator (GECI), which binds to calcium ions and emits fluorescence visualizing intracellular calcium concentration, enables detection of in vivo neuronal firing activity. Various GECIs have been developed and can be chosen for diverse purposes. These GECI-based signals can be acquired by several tools including two-photon microscopy and microendoscopy for precise or wide imaging at cellular to synaptic levels. In addition, the images from GECI signals can be analyzed with open source codes including constrained non-negative matrix factorization for endoscopy data (CNMF_E) and miniscope 1-photon-based calcium imaging signal extraction pipeline (MIN1PIPE), and considering parameters of the imaged brain regions (e.g., diameter or shape of soma or the resolution of recorded images), the real-time activity of each cell can be acquired and linked with animal behaviors. As a result, GECI signal analysis can be a powerful tool for revealing the functions of neuronal circuits related to specific behaviors.
Subject(s)
Animals , Behavior, Animal , Brain , Calcium Channels , Calcium , Carisoprodol , Endoscopy , Fires , Fluorescence , Ions , Microscopy , Neuronal Calcium-Sensor Proteins , Neurons , Neurosciences , Statistics as TopicABSTRACT
BACKGROUND:Neuronal calcium sensor-1 protein has a variety of different neuronal functions and has a high distribution in different areas of the brain. A single residue R102Q mutation in human neuronal calcium sensor-1 protein is demonstrated to be associated with autism disease. The experiment studies have reported that this R102Q mutant has essential conformation changes in local area of the neuronal calcium sensor-1. OBJECTIVE: To wel understand the specific reasons of the R102Q mutation of the neuronal calcium sensor-1 to the conformational dynamic changes. METHODS:Six independent extensive al-atom molecule dynamic simulations during 0-450 ns were conducted. RESULTS AND CONCLUSION: We have found that (1) there is no obvious recombination during the simulations between wild type and mutant type, but R102Q mutant alters the helix and makes the structure of the protein more stable; (2) R102Q mutation alters the salt bridges, reduces the flexibility of L2, and makes L3 extend in hydrophobic crevice. These results reveal that the helix plays an important role in the structural stability, and salt bridge is the important reason for the dynamic changes of neuronal calcium sensor-1 protein. This study may provide a structural insight into the function of protein deficiency associated with R102Q mutant.
ABSTRACT
BACKGROUND:Research front and hotspots of neuronal calcium sensor-1 are always the focus for the researchers in this field. OBJECTIVE:To probe the research front and hotspots of neuronal calcium sensor-1 with the methods of quantitative analysis. METHODS:The methods of co-cited articles analysis and word frequency analysis were used in the article. The objects were 363 articles from Web of Science by US Institute for Scientific Information (ISI) about the neuronal calcium sensor-1 from 1982 to 2014. The network of co-cited articles and keywords was showed in visualization mapping by using CiteSpace III in which the burst nodes represented the high impact hot papers and the most frequently used keywords, and revealed the research frontier and the hot spots of neuronal calcium sensor-1. RESULTS AND CONCLUSION:The physiological functions of neuronal calcium sensor-1 are the research frontier and the hot spots. The transformational point in time spot of the hotspots is during 1994 to 1996, 2000, 2008, 2012;and the different research focus showed in each stage:the structure and characterization of the protein during 1992-2000 and the protein function and the role during 2004-2012 are the research hotspots, while during 2008-2014 the hotspots place extra emphasis on the higher function (e.g. memory) and several diseases(such as schizophrenia, cancer, autism, depression, senile dementia, neuron damage, etc). The determination of the research frontier domains and hot spots of neuronal calcium sensor-1 wil indicate the goal and direction for the further studies.