scholarly journals Emergence of Non-Canonical Parvalbumin-Containing Interneurons in Hippocampus of a Murine Model of Type I Lissencephaly

2020 ◽  
Author(s):  
Tyler G. Ekins ◽  
Vivek Mahadevan ◽  
Yajun Zhang ◽  
James A. D’Amour ◽  
Timothy Petros ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Brain Structures ◽  
Cellular Migration ◽  
Morphological Development ◽  
Type I ◽  
Hippocampal Ca1 ◽  
Migration Disorder ◽  
Fast Spiking ◽  
And Control ◽  
The Impact

ABSTRACTType I lissencephaly is a neuronal migration disorder caused by haploinsuffiency of the LIS1 gene and is characterized in humans by agyria, mislamination of brain structures, developmental delays, and epilepsy. Here, we investigate the impact of LIS1 mutation on the cellular migration, morphophysiology, microcircuitry and genomics of mouse hippocampal CA1 parvalbumin-containing inhibitory interneurons (PV+INTs). We find that WT PV+INTs consist of two physiological subtypes (80% fast-spiking (FS), 20% non-fast-spiking (NFS)) and four morphological subtypes (basket, axo-axonic, bistratified, radiatum-targeting). We also discover that cell-autonomous mutations within interneurons disrupts morphological development of PV+INTs and results in the emergence of a non-canonical “intermediate spiking (IS)” subset of PV+INTs. In the GlobalLis mutant, IS/NFS cells become the dominant PV+INT subtypes (56%) and the percentage of FS cells shrinks to 44%. We also find that IS/NFS cells are prone to entering depolarizing block, causing them to temporarily lose the ability to initiate action potentials and control network excitation, potentially promoting seizures. Finally, single-cell nuclear RNAsequencing of PV+INTs revealed several misregulated genes related to morphogenesis, cellular excitability, and synapse formation.

scholarly journals Emergence of non-canonical parvalbumin-containing interneurons in hippocampus of a murine model of type I lissencephaly

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tyler G Ekins ◽  
Vivek Mahadevan ◽  
Yajun Zhang ◽  
James A D'Amour ◽  
Gülcan Akgül ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Cellular Migration ◽  
Type I ◽  
Hippocampal Ca1 ◽  
Cellular Excitability ◽  
Neuronal Migration Disorder ◽  
Migration Disorder ◽  
Fast Spiking ◽  
And Control ◽  
The Impact

Type I lissencephaly is a neuronal migration disorder caused by haploinsuffiency of the PAFAH1B1 (mouse: Pafah1b1) gene and is characterized by brain malformation, developmental delays, and epilepsy. Here, we investigate the impact of Pafah1b1 mutation on the cellular migration, morphophysiology, microcircuitry, and transcriptomics of mouse hippocampal CA1 parvalbumin-containing inhibitory interneurons (PV+INTs). We find that WT PV+INTs consist of two physiological subtypes (80% fast-spiking (FS), 20% non-fast-spiking (NFS)) and four morphological subtypes. We find that cell-autonomous mutations within interneurons disrupts morphophysiological development of PV+INTs and results in the emergence of a non-canonical ‘intermediate spiking (IS)’ subset of PV+INTs. We also find that now dominant IS/NFS cells are prone to entering depolarization block, causing them to temporarily lose the ability to initiate action potentials and control network excitation, potentially promoting seizures. Finally, single-cell nuclear RNAsequencing of PV+INTs revealed several misregulated genes related to morphogenesis, cellular excitability, and synapse formation.

scholarly journals Aberrant sorting of hippocampal complex pyramidal cells in Type I Lissencephaly alters topological innervation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
James A D'Amour ◽  
Tyler Ekins ◽  
Stuti Ganatra ◽  
Xiaoqing Yuan ◽  
Chris J McBain
Keyword(s):  
Neurodevelopmental Disorder ◽  
Pyramidal Cells ◽  
Brain Structures ◽  
Oscillatory Activity ◽  
Mammalian Brain ◽  
Type I ◽  
Principal Cells ◽  
Disease States ◽  
Hippocampal Ca1

Layering has been a long-appreciated feature of higher order mammalian brain structures but the extent to which it plays an instructive role in synaptic specification remains unknown. Here we examine the formation of synaptic circuitry under cellular heterotopia in hippocampal CA1, using a mouse model of the human neurodevelopmental disorder Type I Lissencephaly. We identify calbindin-expressing principal cells which are mispositioned under cellular heterotopia. Ectopic calbindin-expressing principal cells develop relatively normal morphological features and stunted intrinsic physiological features. Regarding network development, a connectivity preference for cholecystokinin-expressing interneurons to target calbindin-expressing principal cells is diminished. Moreover, in vitro gamma oscillatory activity is less synchronous across heterotopic bands and mutants are less responsive to pharmacological inhibition of cholecystokinin-containing interneurons. This study will aid not only in our understanding of how cellular networks form but highlight vulnerable cellular circuit motifs that might be generalized across disease states.

scholarly journals Aberrant sorting of hippocampal complex pyramidal cells in Type I Lissencephaly alters topological innervation

2020 ◽  
Author(s):  
James A. D’Amour ◽  
Tyler G. Ekins ◽  
Stuti Ghanatra ◽  
Xiaoqing Yuan ◽  
Chris J. McBain
Keyword(s):  
Neurodevelopmental Disorder ◽  
Pyramidal Cells ◽  
Brain Structures ◽  
Oscillatory Activity ◽  
Mammalian Brain ◽  
Type I ◽  
Principal Cells ◽  
Disease States ◽  
Hippocampal Ca1

AbstractLayering has been a long-appreciated feature of higher order mammalian brain structures but the extent to which it plays an instructive role in synaptic specification remains unknown. Here we examine the formation of synaptic circuitry under cellular heterotopia in hippocampal CA1, using a mouse model of the human neurodevelopmental disorder Type I Lissencephaly. We identify calbindin-expressing principal cells which are mispositioned under cellular heterotopia. Ectopic calbindin-expressing principal cells develop relatively normal morphological features and stunted intrinsic physiological features. Regarding network development, a connectivity preference for cholecystokinin-expressing interneurons to target calbindin expressing principal cells is diminished. Moreover, in vitro gamma oscillatory activity is less synchronous across heterotopic bands and mutants are less responsive to pharmacological antagonism of cholecystokinin-containing interneurons. This study will aid not only in our understanding of how cellular networks form but highlight vulnerable cellular circuit motifs that might be generalized across disease states.

Suppressed, but Not Forgotten

2011 ◽  
Vol 70 (1) ◽  
pp. 5-11 ◽  
Author(s):  
Beat Meier ◽  
Anja König ◽  
Samuel Parak ◽  
Katharina Henke
Keyword(s):  
Memory Trace ◽  
Thought Suppression ◽  
Test Phase ◽  
Indirect Test ◽  
Final Test ◽  
Test Experiment ◽  
And Control ◽  
Cue Words ◽  
The Impact

This study investigates the impact of thought suppression over a 1-week interval. In two experiments with 80 university students each, we used the think/no-think paradigm in which participants initially learn a list of word pairs (cue-target associations). Then they were presented with some of the cue words again and should either respond with the target word or avoid thinking about it. In the final test phase, their memory for the initially learned cue-target pairs was tested. In Experiment 1, type of memory test was manipulated (i.e., direct vs. indirect). In Experiment 2, type of no-think instructions was manipulated (i.e., suppress vs. substitute). Overall, our results showed poorer memory for no-think and control items compared to think items across all experiments and conditions. Critically, however, more no-think than control items were remembered after the 1-week interval in the direct, but not in the indirect test (Experiment 1) and with thought suppression, but not thought substitution instructions (Experiment 2). We suggest that during thought suppression a brief reactivation of the learned association may lead to reconsolidation of the memory trace and hence to better retrieval of suppressed than control items in the long term.

Research Participation Experiences of Informants of Suicide and Control Cases

Crisis ◽  
2010 ◽  
Vol 31 (5) ◽  
pp. 238-246 ◽  
Author(s):  
Paul W. C. Wong ◽  
Wincy S. C. Chan ◽  
Philip S. L. Beh ◽  
Fiona W. S. Yau ◽  
Paul S. F. Yip ◽  
...  
Keyword(s):  
Ethical Issues ◽  
Research Participation ◽  
Self Report ◽  
Initial Contact ◽  
Psychological Autopsy ◽  
Autopsy Study ◽  
The People ◽  
And Control ◽  
The Impact

Background: Ethical issues have been raised about using the psychological autopsy approach in the study of suicide. The impact on informants of control cases who participated in case-control psychological autopsy studies has not been investigated. Aims: (1) To investigate whether informants of suicide cases recruited by two approaches (coroners’ court and public mortuaries) respond differently to the initial contact by the research team. (2) To explore the reactions, reasons for participation, and comments of both the informants of suicide and control cases to psychological autopsy interviews. (3) To investigate the impact of the interviews on informants of suicide cases about a month after the interviews. Methods: A self-report questionnaire was used for the informants of both suicide and control cases. Telephone follow-up interviews were conducted with the informants of suicide cases. Results: The majority of the informants of suicide cases, regardless of the initial route of contact, as well as the control cases were positive about being approached to take part in the study. A minority of informants of suicide and control cases found the experience of talking about their family member to be more upsetting than expected. The telephone follow-up interviews showed that none of the informants of suicide cases reported being distressed by the psychological autopsy interviews. Limitations: The acceptance rate for our original psychological autopsy study was modest. Conclusions: The findings of this study are useful for future participants and researchers in measuring the potential benefits and risks of participating in similar sensitive research. Psychological autopsy interviews may be utilized as an active engagement approach to reach out to the people bereaved by suicide, especially in places where the postvention work is underdeveloped.

Using Work Domain Analysis to Evaluate the Impact of Digitization on Command and Control

2008 ◽  
Author(s):  
Daniel P. Jenkins ◽  
Neville A. Stanton ◽  
Paul M. Salmon ◽  
Guy H. Walker
Keyword(s):  
Command And Control ◽  
Domain Analysis ◽  
Work Domain Analysis ◽  
And Control ◽  
The Impact ◽  
Work Domain

Experimental Study of the Impact of Alisma plantago-aquatica Secretions on Pathogenic Bacteria

2014 ◽  
Vol 1 (3) ◽  
pp. 3-7
Author(s):  
O. Zhukorskyy ◽  
O. Hulay
Keyword(s):  
Pathogenic Bacteria ◽  
Initial Density ◽  
Biologically Active ◽  
Erysipelothrix Rhusiopathiae ◽  
Natural Focus ◽  
Test Species ◽  
Popula Tions ◽  
And Control ◽  
The Impact

Aim. To estimate the impact of in vivo secretions of water plantain (Alisma plantago-aquatica) on the popula- tions of pathogenic bacteria Erysipelothrix rhusiopathiae. Methods. The plants were isolated from their natural conditions, the roots were washed from the substrate residues and cultivated in laboratory conditions for 10 days to heal the damage. Then the water was changed; seven days later the selected samples were sterilized using fi lters with 0.2 μm pore diameter. The dilution of water plantain root diffusates in the experimental samples was 1:10–1:10,000. The initial density of E. rhusiopathiae bacteria populations was the same for both experimental and control samples. The estimation of the results was conducted 48 hours later. Results. When the dilution of root diffusates was 1:10, the density of erysipelothrixes in the experimental samples was 11.26 times higher than that of the control, on average, the dilution of 1:100 − 6.16 times higher, 1:1000 – 3.22 times higher, 1:10,000 – 1.81 times higher, respectively. Conclusions. The plants of A. plantago-aquatica species are capable of affecting the populations of E. rhusiopathiae pathogenic bacteria via the secretion of biologically active substances into the environment. The consequences of this interaction are positive for the abovementioned bacteria, which is demon- strated by the increase in the density of their populations in the experiment compared to the control. The intensity of the stimulating effect on the populations of E. rhusiopathiae in the root diffusates of A. plantago-aquatica is re- ciprocally dependent on the degree of their dilution. The investigated impact of water plantain on erysipelothrixes should be related to the topical type of biocenotic connections, the formation of which between the test species in the ecosystems might promote maintaining the potential of natural focus of rabies. Keywords: Alisma plantago-aquatica, in vivo secretions, Erysipelothrix rhusiopathiae, population density, topical type of connections.

Changes in the Population Density of Pathogenic Microorganisms in Response to the Allelopathic Effect of Thypha Latifolia

2014 ◽  
Vol 1 (1) ◽  
pp. 31-36 ◽  
Author(s):  
O. Zhukorskiy ◽  
O. Gulay ◽  
V. Gulay ◽  
N. Tkachuk
Keyword(s):  
Cell Density ◽  
Allelopathic Effect ◽  
Pathogenic Microorganisms ◽  
Sterile Water ◽  
Erysipelothrix Rhusiopathiae ◽  
Pathogenic Leptospira ◽  
Favorable Conditions ◽  
And Control ◽  
The Impact ◽  
Control Samples

Aim. To determine the response of the populations of Erysipelothrix rhusiopathiae and Leptospira interrogans pathogenic microorganisms to the impact of broadleaf cattail (Thypha latifolia) root diffusates. Methods. Aqueous solutions of T. latifolia root diffusates were sterilized by vacuum fi ltration through the fi lters with 0.2-micron pore diameter. The experimental samples contained cattail secretions, sterile water, and cultures of E. rhusiopathiae or L. interrogans. The same amount of sterile water, as in the experimental samples, was used for the purpose of control, and the same quantity of microbial cultures was added in it. After exposure, the density of cells in the experimental and control samples was determined. Results. Root diffusates of T. latifolia caused an increase in cell density in the populations of E. rhusiopathiae throughout the whole range of the studied dilutions (1:10–1:10000). In the populations of the 6 studied serological variants of L. interrogans spirochetes (pomona, grippotyphosa, copenhageni, kabura, tarassovi, canicola), the action of broadleaf cattail root diffusates caused the decrease in cell density. A stimulatory effect was marked in the experimental samples of the pollonica serological variant of leptospira. Conclusions. The populations of E. rhusiopathiae and L. interrogans pathogenic microorganisms respond to the allelopathic effect of Thypha latifolia by changing the cell density. The obtained results provide the background to assume that broadleaf cattail thickets create favorable conditions for the existence of E. rhusiopathiae pathogen bacteria. The reduced cell density of L. interrogans in the experimental samples compared to the control samples observed under the infl uence of T. latifolia root diffusates suggests that reservoirs with broadleaf cattail thickets are marked by the unfavorable conditions for the existence of pathogenic leptospira (except L. pollonica).

Pengaruh Lama Pengasinan Terhadap Kadar Protein Putih Telur Itik

2014 ◽  
Vol 1 (1) ◽  
pp. 36 ◽  
Author(s):  
Siti Fatimah ◽  
Muji Rahayu ◽  
Siti Aminah
Keyword(s):  
Protein Level ◽  
Egg White ◽  
Special Treatment ◽  
Egg White Protein ◽  
Protein Levels ◽  
Duck Egg ◽  
Egg Period ◽  
Graph Presentation ◽  
And Control ◽  
The Impact

Background : Egg  is one of the animal protein source, which has delicious taste, easy to digest and highly nutritious. Besides its affordable price, its supply availability is unquestionable as well. However, due to its short storability, it requires special treatment, such as preserving, to store it for long period. One way to preserve the egg is by pickling egg, which generally requires seven to ten days of marinating. During the process of marinating, there will be a visual change of egg white and yolk. Their structures  will be more solid (the occurrence of thickening process) because salinization will lead to protein denaturalization. Consequently, it has an influence as well towards the content of egg white protein of duck egg. This study is aimed to explore the impact of various time of pickling egg towards egg white protein of duck egg. Method  : The study where takes place in a laboratories, is a true experimental study for the reason that the researcher must provide intervention, hence all of potentially confounding variables are manageable. Samples that had been used in this study are duck eggs which were bought from North Brebes. This study is expected to generate data from four various time of pickling egg and control (no treatment). Since there are four samples, accordingly the number of data resulted are twenty. The resulted data will be descriptively presented in table, graph, presentation, and narration. Result  : Protein level examination within duck white egg shows changes  in protein levels that occurs in every variation of pickling egg time, where the average results of the assay of duck egg white protein is 14.94% without treatment (control), in five days of pickling time is 13.68%, in seven days of pickling time is 13.29%, in nine days of pickling time is 12.87% and eleven days of pickling time is 12.78%. Conclusion  : There is a significant impact among the period of pickling time to the protein level degradation of duck white egg. Keywords : Duck egg, period of pickling time, level protein of duck white egg.

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