22 research outputs found
Erratum: Author Details
No full textThe list of authors of the manuscript titled: Plasma Malondialdehyde Level Correlates with Antioxidant Capacity after Acute Red Wine Consumption in Healthy Young Adults which was published in Volume 34 Number 2, 2013, pages 118-121 of the Nigerian Journal of Nutritional Sciences was not complete. The correct list of authors of this paper, as submitted and accepted for publication were Emokpae MA, Arogundade A and Adumanya SC.We regret the inadvertent omission of the affected author
Things fall into place
No full textThis paper is imperative. A response to an invitation/provocation to think about "things fall apart": the question mark inviting each respondent tio use the iconic title by the iconic author to launch our own musings. The authors choose to present a collage of a number of conversations and reflections that span both years and fleeting moments, that have taken place in person, over the phone, via facebook. Parts of these were presented at the 2013 Africa Day panel discussion,parts were left out and now have the chance to reach beyond ourselves.
PERCEIVED EFFECTS OF PHARMACOLOGICAL ERGOGENIC AIDS ON SPORTS PERFORMANCE AND HEALTH OF NIGERIAN UNIVERSITY ATHLETES
No full textThe study investigates the perceived effects of pharmacological ergogenic aids on health and sports performance of Nigerian university athletes with a view to increasing the credibility of athletes’ performance. The study adopted descriptive survey design. A total of 332 university athletes were randomly sampled during Nigeria University Games from four popular groups of sports: track and field athletics ball/racket and stick games, combat sports and aquatic sports. A self- designed and validated questionnaire which focuses on state and pattern of use of pharmacological ergogenic aids and their perceived effects on sports performance and health was used for this study. Percentage and chi-square statistics were used to analyze the data. The results showed that stimulants, narcotics, anabolic steroids and depressants are types of pharmacological ergogenic aids used by university athletes. The results further showed that the perceived effects of ergogenic aids on health and sports performance was not significant (X2=7.82, p>0.05.The study concluded that ergogenic aids had adverse effects including weight gain and insomnia on both health and sports performance. It was therefore recommended that drug diagnosing laboratory equipment should be available every in NUGA competition to detect doping violators and include drug education in the general school curriculum
Things fall into place
No full textThis paper is imperative. A response to an invitation/provocation to think about "things fall apart": the question mark inviting each respondent tio use the iconic title by the iconic author to launch our own musings. The authors choose to present a collage of a number of conversations and reflections that span both years and fleeting moments, that have taken place in person, over the phone, via facebook. Parts of these were presented at the 2013 Africa Day panel discussion,parts were left out and now have the chance to reach beyond ourselves.
PREreview of "Ciliary ARL13B prevents obesity in mice"
No full textThis Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/8308506.
This review reflects comments and contributions from Femi Arogundade, Elena Sena, Luciana Gallo & Olakunle Jaiyesimi. Review synthesized by Jonny Coates.
This study delves into the function of the ARL13B protein (a regulatory GTPase found in cilia) in maintaining energy balance. By examining mice expressing an altered ARL13B variant lacking ciliary localization, the study uncovers that these mice become obese due to issues with metabolism and overeating. It's suggested that ARL13B has a distinct role within cilia that influences body weight and food consumption, separate from its GEF activity for ARL3.Additionally, the study proposes that ARL13B's interaction with INPP5E in cilia plays a role in energy balance, offering insights into cilia-mediated signaling pathways related to energy regulation.
Major comments:
We do not have any major comments for this article
Minor comments:
Write out in full for first use of POMC and MC4R
Discuss the differences between male and female body weight (fig 1)
Arl13bhnn allele would flow better if written as "Arl13bhnn allele bearing mice". Moreover, when discussing in-text, the term "cilia-excluded ARL13B" would help readers follow better.
Repeating the information that the mutation V358A in ARL13B excludes ARL13B from the cilia when mentioned first in the results would aid in readability.
When discussing fig 1 in-text, the descriptions are shifted (i.e. Fig 1B is described as Fig 1C)
"The feeding behavior in Arl13bV358A/V358A mice implicates the hypothalamus is involved" should read as "The feeding behavior in Arl13bV358A/V358A mice implies that the hypothalamus is involved".
Abbreviations used in the legend of Fig 2 are not used in the figure itself.
Figure 2 would benefit from the addition of appropriate blanks to serve as controls for the antibodies used
Additionally, figure 4 would also benefit from a negative control
Suggestions for future studies
Integration of metabolomics analysis for the assessment of metabolic fate will provide molecular mechanisms underlying the phenotypes of interest
Competing interests
The author declares that they have no competing interests
Taxpayers rights protection in Nigeria
No full textThis dissertation provides an overview of the rights of taxpayers in Nigeria. The author analyses the domestic and international framework of taxpayers' rights protection, reviews the history of tax regimes in Nigeria and the broader context of human rights, highlighting those areas that require further attention
PREreview of "NOTCH3 drives meningioma tumorigenesis and resistance to radiotherapy"
No full text<p><strong>This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at <a href="https://prereview.org/reviews/10044659">https://prereview.org/reviews/10044659</a>.</strong></p>
<p>This review reflects comments and contributions from Marta Oliva Santiago & Femi Arogundade. Review synthesized by Arpita Ghosh and Garima Jain.</p><p>The study investigates the role of NOTCH3 in driving the tumorigenesis of meningiomas and their resistance to radiotherapy, highlighting potential therapeutic avenues for treating these tumors. The research encompasses human, dog, and mouse models, uncovering the involvement of NOTCH3 in angiogenesis, cancer stem cell properties, and its relevance across various meningioma grades and molecular groups. The study suggests that NOTCH3 inhibition could be a promising strategy for addressing meningiomas resistant to standard treatments, presenting an opportunity for further research and potential clinical applications.</p><p>Major comments:</p><ul><li><p>The study reports that NOTCH3 plays a critical role in driving the formation of meningiomas and their resistance to radiotherapy. This phenomenon is observed in various cell types across humans, dogs, and mice.</p></li><li><p>The study employs various molecular and genetic techniques to understand the role of NOTCH3 in meningioma development and resistance to therapy. It highlights the potential for NOTCH3 as a therapeutic target and emphasizes the need for further research and clinical testing to validate these findings in human patients.</p></li><li><p>The findings suggest that targeting NOTCH3 could be a new therapeutic strategy to treat meningiomas that do not respond to standard treatments. This could be a significant breakthrough for a common intracranial tumor.</p></li><li><p>The study indicates that the vasculature in meningiomas is composed of both endothelial cells from the microenvironment and tumor cells. NOTCH3 signaling between these mural cells and endothelial cells appears to contribute to meningioma migration into surrounding tissues. This migration pattern could explain why some meningiomas recur after standard treatments.</p></li><li><p>NOTCH3+ meningioma mural cells exhibit characteristics of cancer stem cells, such as promoting cell proliferation, clonogenic growth, angiogenesis, and resistance to treatment. This highlights the significance of NOTCH3 in meningioma pathogenesis.</p></li><li><p>The study acknowledges that other stem or progenitor cells might contribute to meningioma tumorigenesis, especially in meningiomas with intact NF2. The presence of PTGDS cells is mentioned, suggesting heterogeneity in meningioma stem cells.</p></li><li><p>NOTCH3 and NOTCH3 target genes are enriched in high-grade and recurrent meningiomas. However, NOTCH3 signaling and NOTCH3+ cells are identified in meningiomas across all grades and molecular groups.</p></li><li><p>While the safety and efficacy of NOTCH3 inhibition in humans have not been defined, the study suggests that it could be a promising systemic therapy for treating resistant meningiomas, as Notch3 knockout mice are viable and fertile.</p></li></ul><p>Minor comments:</p><ul><li><p>How were the human meningioma tissue samples collected and characterized? Were there any specific criteria for the selection of samples, such as tumor grade or molecular subtypes?</p></li><li><p>What were the specific details of the radiation therapy administered to the experimental models, including the dose, duration, and fractionation scheme?</p></li><li><p>How was the resistance to radiotherapy assessed and quantified in the study?</p></li><li><p>What assays or experiments were conducted to elucidate the mechanisms by which NOTCH3 drives tumorigenesis in meningiomas?</p></li><li><p>How were NOTCH3-positive mural cells' cancer stem cell characteristics determined and characterized?</p></li><li><p>How were the angiogenic properties of NOTCH3+ mural cells and their interactions with endothelial cells assessed and quantified? Were there any additional factors involved in this process that were not discussed in the study?</p></li><li><p>How was patient data integrated with the experimental findings to make the connections between NOTCH3 expression, tumor aggressiveness, and clinical outcomes? Were any specific clinical or genetic factors considered in this integration?</p></li><li><p>What specific therapeutic approaches could be developed based on the findings in this study, and what is their potential impact on patient outcomes?</p></li><li><p>The study mentions that the safety and efficacy of selective NOTCH3 inhibition have not been defined in humans. What would be the next steps in terms of preclinical and clinical trials to assess the safety and efficacy of NOTCH3 inhibition in treating meningiomas? Are there any potential side effects or risks associated with targeting NOTCH3 that need to be investigated?</p></li></ul><p>Comments on reporting:</p><ul><li><p>The paper contains extensive information, and it would be beneficial to summarize the key findings in the discussion section, emphasizing the clinical and biological implications of the results.</p></li></ul><p>Suggestions for future studies:</p><ul><li><p>Perform high-throughput drug screening to identify potential therapeutic agents that can target specific pathways identified in this study. Developing targeted therapies that can overcome NOTCH3-mediated resistance to radiotherapy could be a significant breakthrough.</p></li><li><p>Investigate the role of other genetic and epigenetic alterations in meningioma development. This could include whole-genome sequencing, epigenome mapping, and transcriptome profiling to identify additional genetic and epigenetic drivers of meningioma progression.</p></li><li><p>Investigate the potential of immunotherapy in treating meningiomas. Understanding the immune microenvironment in these tumors and exploring immunotherapeutic strategies, such as immune checkpoint inhibitors or tumor-infiltrating lymphocyte therapies, could be promising.</p></li><li><p>Conduct prospective, large-scale clinical studies to validate the findings of this preprint in a broader patient population. This would help determine the clinical relevance of NOTCH3 as a therapeutic target and resistance factor for radiotherapy.</p></li><li><p>Undertake long-term follow-up studies of meningioma patients to assess the recurrence rates, survival outcomes, and late effects of radiotherapy, especially in cases involving NOTCH3 mutations. This will provide insights into the clinical relevance and long-term consequences of therapy resistance.</p></li><li><p>Identify and validate predictive biomarkers for therapy response and resistance. Understanding which patients are more likely to benefit from specific treatments can help personalize therapeutic strategies.</p></li><li><p>Explore the possibility of molecular subtyping of meningiomas to tailor treatment strategies. Different meningioma subtypes may have distinct genetic profiles and responses to therapy.</p></li><li><p>Assess patient-reported outcomes and quality of life in long-term meningioma survivors, particularly those who have received radiotherapy. This can provide valuable insights into the patient experience and guide treatment decisions.</p></li></ul>
<h2>Competing interests</h2>
<p>
The author declares that they have no competing interests.
</p>
PREreview of "Dynein and dynactin move long-range but are delivered separately to the axon tip"
No full textThis Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/8362691.
This review reflects comments and contributions from Kamaldeep Singh, Prithviraj Rajebhosale, Luciana Gallo, Ryan Cubero & Femi Arogundade. Review synthesized by Kamaldeep Singh.
In this study, Fellows et al. investigated the motility of endogenously-tagged dynein motors and its regulators along the length of the axons using live imaging of neuron-inducible human-stem cell lines (iNeurons) as a model system. Using highly inclined and laminated optical sheet (HILO) imaging of iNeurons, they show that dynein and dynactin are transported at different speeds to the distal tip of the axon. Further, use of SNAP and Halo-tag conjugated with highly stable fluorophores also allowed them to show that single molecules of dynein and dynactin can traverse the entire length of the axon (>500 um). In summary, this study has contributed in advancing the cell biological understanding of dynein and its regulators in mammalian axons.
We believe that the following positive aspects make the findings of the study strong and convincing:
Use of neuron-inducible human stem cell-derived iNeurons as a model system is a significant advantage as it provides a better understanding of mammalian cell biology for studying axonal transport compared to traditional cancer cell lines.
Use of microfluidic devices to separate axons from the somatodendritic compartments allows a convincing and clear demonstration of retrograde and anterograde transport in the axons and dynamics thereof.
Use of CRISPR to endogenously tag the dynein heavy chain and the ARP11 subunit of dynactin with a SNAP and HaloTag allowed the authors to selectively label the motos with high spatio-temporal resolution. This not only aided in imaging dynein/dynactin at a near single-molecule level but also allowed them to figure that single molecules of dynein and dynactin can traverse the entire length of the axon (>500um).
The photobleaching analysis on dynein spots in iNeurons provides valuable insights into the possible number of dynein molecules per cargo (which also agrees well with recent measurements of dynein number on endosomes in literature) and supports the claim of detecting single molecules under the given experimental conditions.
We also noted several points regarding the study and the manuscript (as major or minor comments) which if addressed, could possibly make the study better:
Major comments:
The authors observed mostly 1 and 2 step bleaching for dynein (Figure 2). Here, while they commented on the two step events being predominant and representative of the cytoplasmic dynein dimer, an explanation for the single bleaching events is lacking. Is it possible that these could be Halo-tagged dynein molecules dimerized with endogenous, untagged dynein from monoallelic targeting by CRISPR? It would therefore be nice to clarify and show the data that validates their CRISPR knock-in efficiency.
The authors mention: "We saw many distinct dynein spots in the axonal compartment, most of which were diffusing, often along microtubules (Fig S2A, Video 4)." How did the authors determine that these events were diffusive and that they occured along microtubules?
Minor comments:
Figure 3 is incorrectly labeled as Figure 2 in the legend. Kindly correct this.
"Thought" is misspelled as "thught" in the last paragraph of Introudction section.
Fig 3C is incorrectly addressed as "Fig 3B" under the results section "Dynein moves long range".
In the videos attached along with the manuscript: It would be nice if there could be additional markers - for instance arrows tracking the particles (just like box on the spot where photobleaching was performed) - to help readers focus on the main point the authors are trying to make with respect to a given video.
While the microfluidic devices utilized in the study might be standard in the trafficking field, it would be nice if the authors could provide a detailed description such as the devices' exact dimensions and manufacturer/supplier details.
Authors have already hinted towards many unanswered questions, possible experiments and also listed anticipated outcomes for many such questions. Here are a few suggestions for lines of investigation that one could undertake in the future research:
As it has already been emphasized by authors, LIS1 is an important regulator of dynein activation. Therefore, simultaneous imaging of LIS1 and dynein might allow authors to identify whether the pausing of dynein is due to exchange of LIS1 within the complexes. Similar studies conducted with dynein together with other dynein cofactors, activators, or even kinesins will be useful to address many unanswered questions in the field.
Given that the authors can compartmentalize the somatodendrites and axons, it would also be interesting to know whether supply of dynein at the distal tip is regulated in response to different stimuli for e.g. in response to perturbations in neuronal activity.
We wish the authors best of luck for all of their future research endeavours!
Competing interests
The author declares that they have no competing interests
PREreview of "A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria"
No full text<p><strong>This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at <a href="https://prereview.org/reviews/8431146">https://prereview.org/reviews/8431146</a>.</strong></p>
<p>This review reflects comments and contributions from Marina Schernthanner, Femi Arogundade and Pablo Ranea-Robles. Review synthesized by Jonny Coates.</p>
<p>The study leverages the phenotype presented by the renal Glut2 KO mice (glycosuria with normal glycemia) to investigate how the body senses this glucose loss and the mechanisms behind metabolic homeostasis processes that lead to enhanced glucose production so glycemia remains stable. The use of a genetically modified mouse model with renal Glut2 knockout provides a controlled system for studying the specific role of renal glucose transporters in glucose homeostasis. The study involves various methods, including measurements of glucose production, metabolomics, gene expression related to the hypothalamic-pituitary-adrenal axis, afferent renal nerve ablation, and analysis of secreted proteins. The authors point to a kidney/hypothalamus axis and suggest the involvement of different acute phase proteins in this homeostatic response. The limitations of the study are acknowledged, and further research is suggested to delve deeper into the role of secretory proteins and the specific source of endogenous glucose production after afferent renal denervation. The manuscript is well written and the results are potentially of interest. The study's findings have potential implications for the field of diabetes treatment, as they suggest a mechanism that may explain why SGLT2 inhibitors don't achieve their full potential in lowering blood glucose levels. However, we think that some of the conclusions are merely based on descriptive assessments of changes occurring in the renal Glut2 KO mice. There are a lack of details in the reporting of some of the results and, in particular, in the discussion section, that would also require a bit more explanation from the authors. Right now, it could be hard for the reader to place this research in context. We have summarized our comments below</p>
<p>Major comments:</p>
<ul>
<li>
<p>The study mentions the use of male and female mice, but it's important to know the sample sizes for each experimental group and how gender might influence the results. Additionally, the authors should provide more details about the control groups and their matching criteria to ensure the validity of comparisons. Moreover, the exact genetic information for the knockout mice i.e. what is the CreER driver that makes it kidney-specific? Is missing. It is currently inconsistent in terms of sex and age of mice used for different experiments. </p>
</li>
</ul>
<p>Minor comments:</p>
<ul>
<li>
<p>While the metabolomics analysis is described, more information is needed about the biological significance of the changes observed in the metabolites. How do these changes relate to the compensatory glucose production, and are they causally linked?</p>
</li>
<li>
<p>The paper would benefit from improved organization and clarity, particularly in the results and discussion sections. </p>
</li>
<li>
<p>Crh+ cells in control image of fig 2 are not clear. The authors could consider highlighting the are where these cells are present, or add an inset showing a zoomed image of some positive cells</p>
</li>
<li>
<p>How specific is the use of capsaicin to selectively suppress afferent renal nerve activity? Does this impact other neurons? Either citations or experimental data should be included here. </p>
</li>
<li>
<p>The conditions of mice in Sup Fig. 1 are not clear and should be stated clearly in this part of the text and in the figure legend.</p>
</li>
<li>
<p>The study is transparent about its limitations and raises important questions for future research. This acknowledgment of limitations contributes to the scientific rigor of the work.</p>
</li>
<li>
<p>While control groups are mentioned, it's not clear how these controls were chosen or matched to the experimental group. Further information is needed on how these controls were used to make valid comparisons.</p>
</li>
<li>
<p>While the study describes the experimental procedures in detail, it's essential to provide information on how many times these experiments were replicated to assess the reproducibility of the results. This is especially crucial given the complex methods used.</p>
</li>
<li>
<p>Blocking the HPA axis and assessing responses in KO and WT mice would strengthen the data in Fig 2</p>
</li>
<li>
<p>Investigating or showing the levels of glucagon and adrenaline to delineate mechanisms of tissue-specific glucose production would further strengthen the data presented. </p>
</li>
<li>
<p>Is it possible to measure glucose production under denervation conditions? That would support the conclusion if the increased glucose production is blunted </p>
</li>
<li>
<p>Not everyone might be familiar with the abbreviation 2D-DIGE. Explaining this before first use would be beneficial. </p>
</li>
<li>
<p>Supp fig 2 could be fused with Fig 4 to make the argument more convincing.</p>
</li>
<li>
<p>The authors state that "It is possible that afferent renal denervation in the present study attenuated only hepatic glucose production through the hypothalamus without affecting the compensatory increase in renal (local) glucose production". Addressing this would significantly strengthen the manuscript, particularly given that the title includes "hypothalamus-kidney axis". </p>
</li>
</ul>
<p>Comments on reporting:</p>
<ul>
<li>
<p>The paper mentions the use of statistical tests but lacks information on the specific statistical tests performed for each analysis. It's crucial to provide details on the tests used, assumptions made, and how p-values were adjusted for multiple comparisons, if applicable.</p>
</li>
</ul>
<p>Suggestions for future studies:</p>
<ul>
<li>
<p>Extend the research to human subjects, particularly individuals with diabetes treated with SGLT2 inhibitors. Investigate whether similar mechanisms and pathways are at play in humans, and whether these findings have clinical relevance.</p>
</li>
<li>
<p>Investigate the specific roles of secreted proteins, such as acute phase proteins and major urinary proteins, in glucose regulation and potential interactions with the kidney-hypothalamus axis.</p>
</li>
<li>
<p>Explore how the kidney-hypothalamus axis integrates with other nervous system and endocrine signals involved in glucose regulation, such as insulin and glucagon.</p>
</li>
<li>
<p>Conduct in-depth studies on the impact of afferent renal nerve activity on glucose homeostasis and the signaling pathways involved. Investigate the role of sensory nerves in detecting glycosuria and triggering compensatory responses.</p>
</li>
</ul>
<p>Competing interests</p>
<p>The author declares that they have no competing interests.</p>
PREreview of "The synapsin-dependent vesicle cluster is crucial for presynaptic plasticity at a glutamatergic synapse in male mice"
No full textThis Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/8376891.
This review reflects comments and contributions from Alberto J. Gonzalez-Hernandez, Ryan Cubero & Femi Arogundade. Review synthesized by Ryan Cubero.
The study builds up on a previous study (Owe et al., 2009) that observed impaired frequency facilitation and reduced distal vesicle density in symptomatic synapsin I/II double knockout mice, and fills the gap by unraveling the role of synapsins in the presynaptic mediated plasticity by evaluating the effects of the total loss of synapsins using a triple KO for synapsin I, II and III (SynTKO) in a region of the brain which expresses synapsin III isoform in adult male mice (hippocampal mossy fibers - CA3 glutamatergic synapses). The study follows rigorous ethical and methodological guidelines, utilizing various experimental techniques, including electrophysiological recordings and transmission electron microscopy, to comprehensively analyze synaptic properties in synapsin triple knockout mice. The study reveals that the absence of all synapsin isoforms leads to altered excitability, vesicle organization, and plasticity in mossy fiber boutons, providing insights into the critical role of synapsins in synaptic function and plasticity.
Positive aspects of the paper:
The findings offer valuable insights into how the absence of all synapsin isoforms affects synaptic properties, potentially advancing our knowledge of neurological conditions related to synaptic dysfunction.
The study employs a well-structured study design, utilizing two age groups (presymptomatic and symptomatic) and comparing C57BL/6J control mice with SynTKO mice. This design allows for the investigation of changes before and after the onset of epileptic seizures in SynTKO animals.
The study rigorously examines synaptic function and structure, employing various assays and statistical analyses. This scientific rigor strengthens the validity of the results.
The use of blinding during data analysis is a positive aspect of the study. The experimenter was blinded to the treatment of slices, ensuring that the analysis is objective and not influenced by prior knowledge.
The authors reported the study in accordance with the SAGER guidelines and ARRIVE guidelines 2.0. Such practices should be recognized and highly commended.
Aspects that need to be addressed:
The measurements of Paired Pulse Ratio need to be improved. In Figure 1-2 panels b and c, the SynTKO condition has a replicate out of the range (which could be a potential outlier). This can be potentially addressed by increasing the number of replicates to really depict a better representation of the data dispersion. Furthermore, for panel c, the representative traces should be replaced to ones that represent the median. Ideally, the point of the condition selected for the trace can be highlighted in the graph (e.g. clear fill and same color outline).
In Figure 3c, the authors find a peculiar normalized fEPSP dynamics in SynTKO mice where the fEPSP slowly reaches a peak and slowly decreases, compared to control mice where the peak is reached immediately and decreases abruptly. Perhaps, the authors can discuss what could cause this altered LTP maintenance, given that there is reduced facilitation and PTP, but unimpaired paired-pulse ratio.
Minor comments:
In Figure 1c, the related text says "In SynTKO the amplitudes reached a plateau after 15 stimuli, whereas in WT animals, the amplitudes increased until the end of the 1 Hz stimulation". However, in the plot, there is a plateau for the WT condition around 20-25 stimuli. This sentence needs to be clarified or omitted if the data did not clearly depict this continuous increase.
As a general but minor comment, the representative traces of individual experiments should represent points close to the median (or average) and the point where the trace comes from can be highlighted in the plot.
The TEM images seem to show altered structural abnormalities in mossy fiber boutons in SynTKO mice compared to controls. Were there observed differences in synaptic bouton density?
Comments on reporting:
The statistical analyses are reported correctly in the methods section and table 5. Excluded recordings were also properly justified and detailed in table 6.
Suggestions for future studies:
In this mossy fiber-CA3 synapse, which has been reported to be highly plastic, it would be interesting to also explore what happens in the SynTKO model in presynaptic long term depression (caused by a low frequency stimulation protocol).
Inspecting potential differences in glutamate receptors in mossy fiber presynaptic boutons between SynTKO and control mice could help elucidate the observed differences in synaptic physiology.
Future experiments aiming to understand the role of synapsins (or the lack thereof) in inhibitory neurons will give us a clearer picture of the role of synapsins in synaptic function. It will also be interesting to explore how network connectivity is altered due to total loss of synapsins.
Competing interests
The author declares that they have no competing interests
