scholarly journals Aberrant Cortical Activity In Multiple GCaMP6-Expressing Transgenic Mouse Lines

2017 ◽  
Author(s):  
Nicholas A. Steinmetz ◽  
Christina Buetfering ◽  
Jerome Lecoq ◽  
Christian R. Lee ◽  
Andrew J. Peters ◽  
...  
Keyword(s):  
Transgenic Mouse ◽  
Activity Patterns ◽  
Neuronal Responses ◽  
Interictal Spikes ◽  
Calcium Sensors ◽  
Generalized Seizures ◽  
Affected Mouse ◽  
Underlying Mechanisms ◽  
And Behavior ◽  
Mouse Lines

AbstractTransgenic mouse lines are invaluable tools for neuroscience but as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically-encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, though rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study.

scholarly journals Transmission of tauopathy strains is independent of their isoform composition

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhuohao He ◽  
Jennifer D. McBride ◽  
Hong Xu ◽  
Lakshmi Changolkar ◽  
Soo-jung Kim ◽  
...  
Keyword(s):  
Human Brain ◽  
Transgenic Mouse ◽  
Mouse Line ◽  
Cell Type ◽  
Transgenic Mouse Line ◽  
Adult Human ◽  
Tau Isoforms ◽  
Underlying Mechanisms ◽  
Mouse Lines

AbstractThe deposition of pathological tau is a common feature in several neurodegenerative tauopathies. Although equal ratios of tau isoforms with 3 (3R) and 4 (4R) microtubule-binding repeats are expressed in the adult human brain, the pathological tau from different tauopathies have distinct isoform compositions and cell type specificities. The underlying mechanisms of tauopathies are unknown, partially due to the lack of proper models. Here, we generate a new transgenic mouse line expressing equal ratios of 3R and 4R human tau isoforms (6hTau mice). Intracerebral injections of distinct human tauopathy brain-derived tau strains into 6hTau mice recapitulate the deposition of pathological tau with distinct tau isoform compositions and cell type specificities as in human tauopathies. Moreover, through in vivo propagation of these tau strains among different mouse lines, we demonstrate that the transmission of distinct tau strains is independent of strain isoform compositions, but instead intrinsic to unique pathological conformations.

scholarly journals Toward Understanding the Diverse Roles of Perisomatic Interneurons in Epilepsy

2021 ◽  
pp. 153575972110536
Author(s):  
Barna Dudok ◽  
Peter M. Klein ◽  
Ivan Soltesz
Keyword(s):  
Transgenic Mouse ◽  
Activity Patterns ◽  
Epileptic Seizures ◽  
Aminobutyric Acid ◽  
Spike Generation ◽  
Basket Cells ◽  
Subcellular Domains ◽  
Mouse Lines ◽  
Epileptic Networks

Epileptic seizures are associated with excessive neuronal spiking. Perisomatic γ-aminobutyric acid (GABA)ergic interneurons specifically innervate the subcellular domains of postsynaptic excitatory cells that are critical for spike generation. With a revolution in transcriptomics-based cell taxonomy driving the development of novel transgenic mouse lines, selectively monitoring and modulating previously elusive interneuron types is becoming increasingly feasible. Emerging evidence suggests that the three types of hippocampal perisomatic interneurons, axo-axonic cells, along with parvalbumin- and cholecystokinin-expressing basket cells, each follow unique activity patterns in vivo, suggesting distinctive roles in regulating epileptic networks.

Generation of inducible hepatitis C virus transgenic mouse lines

2006 ◽  
Vol 44 (01) ◽  
Author(s):  
E Ernst ◽  
K Schönig ◽  
H Bläker ◽  
W Stremmel ◽  
J Encke
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Transgenic Mouse ◽  
Mouse Lines

scholarly journals Sound-identity processing in early areas of the auditory ventral stream in the macaque

2012 ◽  
Vol 107 (4) ◽  
pp. 1123-1141 ◽  
Author(s):  
Paweł Kuśmierek ◽  
Michael Ortiz ◽  
Josef P. Rauschecker
Keyword(s):  
Rhesus Macaques ◽  
Population Analysis ◽  
Activity Patterns ◽  
Dorsal Stream ◽  
Stimulus Onset ◽  
Ventral Stream ◽  
Underlying Mechanisms ◽  
Species Specific ◽  
Rostral Region ◽  
Identity Processing

Auditory cortical processing is thought to be accomplished along two processing streams. The existence of a posterior/dorsal stream dealing, among others, with the processing of spatial aspects of sound has been corroborated by numerous studies in several species. An anterior/ventral stream for the processing of nonspatial sound qualities, including the identification of sounds such as species-specific vocalizations, has also received much support. Originally discovered in anterolateral belt cortex, most recent work on the anterior/ventral pathway has been performed on far anterior superior temporal (ST) areas and on ventrolateral prefrontal cortex (VLPFC). Regions of the anterior/ventral stream near its origin in early auditory areas have been less explored. In the present study, we examined three early auditory regions with different anteroposterior locations (caudal, middle, and rostral) in awake rhesus macaques. We analyzed how well classification based on sound-evoked activity patterns of neuronal populations replicates the original stimulus categories. Of the three regions, the rostral region (rR), which included core area R and medial belt area RM, yielded the greatest classification success across all stimulus classes or between classes of natural sounds. Starting from ∼80 ms past stimulus onset, clustering based on the population response in rR became clearly more successful than clustering based on responses from any other region. Our study demonstrates that specialization for sound-identity processing can be found very early in the auditory ventral stream. Furthermore, the fact that this processing develops over time can shed light on underlying mechanisms. Finally, we show that population analysis is a more sensitive method for revealing functional specialization than conventional types of analysis.

scholarly journals Perceptual detection depends on spike count integration

2019 ◽  
Author(s):  
Jackson J. Cone ◽  
Morgan L. Bade ◽  
Nicolas Y. Masse ◽  
Elizabeth A. Page ◽  
David J. Freedman ◽  
...  
Keyword(s):  
Neural Networks ◽  
Cerebral Cortex ◽  
Visual Cortex ◽  
Recurrent Neural Networks ◽  
Neural Circuit ◽  
Visual Detection ◽  
Spike Count ◽  
Neuronal Responses ◽  
Neuronal Populations ◽  
And Behavior

AbstractWhenever the retinal image changes some neurons in visual cortex increase their rate of firing, while others decrease their rate of firing. Linking specific sets of neuronal responses with perception and behavior is essential for understanding mechanisms of neural circuit computation. We trained mice to perform visual detection tasks and used optogenetic perturbations to increase or decrease neuronal spiking primary visual cortex (V1). Perceptual reports were always enhanced by increments in V1 spike counts and impaired by decrements, even when increments and decrements were delivered to the same neuronal populations. Moreover, detecting changes in cortical activity depended on spike count integration rather than instantaneous changes in spiking. Recurrent neural networks trained in the task similarly relied on increments in neuronal activity when activity was costly. This work clarifies neuronal decoding strategies employed by cerebral cortex to translate cortical spiking into percepts that can be used to guide behavior.

Social Epigenetics of Human Behavior

2018 ◽  
Author(s):  
Daniel E. Adkins ◽  
Kelli M. Rasmussen ◽  
Anna R. Docherty
Keyword(s):  
Social Dynamics ◽  
Black Box ◽  
Mediating Role ◽  
Current State ◽  
Genome Wide ◽  
Social Adversity ◽  
Underlying Mechanisms ◽  
And Behavior ◽  
Negative Health Outcomes ◽  
Downstream Gene Expression

It is well established that extreme social adversity can lead to negative health outcomes decades after the resolution of the precipitating environmental insult. Although the underlying mechanisms through which such adversity gets “under the skin” to become biologically embedded have long been considered a black box, recent research has indicated an important mediating role for epigenetic mechanisms—molecular modifications that regulate gene activity without changing the DNA sequence. With technical and scientific developments now enabling genome-wide epigenetic studies in humans, behavioral researchers have an unprecedented opportunity to empirically map the ways in which social dynamics become epigenetically embedded, influencing downstream gene expression, health, and behavior. This chapter examines the current state of social epigenetics research and discusses the opportunities and challenges facing this emerging field.

A regulatory region from the mouse Hox-2.2 promoter directs gene expression into developing limbs

Development ◽  
1991 ◽  
Vol 112 (3) ◽  
pp. 807-811 ◽  
Author(s):  
K. Schughart ◽  
C.J. Bieberich ◽  
R. Eid ◽  
F.H. Ruddle
Keyword(s):  
Gene Expression ◽  
Transgenic Mouse ◽  
Reporter Gene ◽  
Developmental Stages ◽  
Regulatory Region ◽  
Homeobox Gene ◽  
Regulatory Elements ◽  
Body Region ◽  
Lacz Gene ◽  
Mouse Lines

To characterize cis-acting regulatory elements of the murine homeobox gene, Hox-2.2, transgenic mouse lines were generated that contained the LacZ reporter gene under the control of different fragments from the presumptive Hox-2.2 promoter. A promoter region of 3600 base pairs (bp) was identified, which reproducibly directed reporter gene expression into specific regions of developing mouse embryos. At 8.5 days postcoitum (p.c.) reporter gene activity was detected in posterior regions of the lateral mesoderm and, in subsequent developmental stages, expression of the LacZ gene was restricted to specific regions of the developing limb buds and the mesenchyme of the ventrolateral body region. This pattern of Hox-2.2-LacZ expression was found in all transgenic embryos that have been generated with the 3.6 kb promoter fragment (two founder embryos and embryos from five transgenic lines). In addition, embryos from two transgenic mouse lines expressed the reporter gene at low levels in the developing central nervous system (CNS). Our results are consistent with the idea that in addition to their presumptive role in CNS and vertebrae development, Hox-2.2 gene products are involved in controlling pattern formation in developing limbs.

scholarly journals Characterization of Learning, Motivation, and Visual Perception in Five Transgenic Mouse Lines Expressing GCaMP in Distinct Cell Populations

2020 ◽  
Vol 14 ◽  
Author(s):  
Peter A. Groblewski ◽  
Douglas R. Ollerenshaw ◽  
Justin T. Kiggins ◽  
Marina E. Garrett ◽  
Chris Mochizuki ◽  
...  
Keyword(s):  
Visual Perception ◽  
Transgenic Mouse ◽  
Learning Motivation ◽  
Cell Populations ◽  
Distinct Cell ◽  
Mouse Lines
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