Vacuolar H+-ATPases (V-ATPases) transport protons across cellular membranes to acidify various organelles. ATP6V0A1 encodes the a1-subunit of the V0 domain of V-ATPases, which is strongly expressed in neurons. However, its role in brain development is unknown. Here we report four individuals with developmental and epileptic encephalopathy with ATP6V0A1 variants: two individuals with a de novo missense variant (R741Q) and the other two individuals with biallelic variants comprising one almost complete loss-of-function variant and one missense variant (A512P and N534D). Lysosomal acidification is significantly impaired in cell lines expressing three missense ATP6V0A1 mutants. Homozygous mutant mice harboring human R741Q (Atp6v0a1R741Q) and A512P (Atp6v0a1A512P) variants show embryonic lethality and early postnatal mortality, respectively, suggesting that R741Q affects V-ATPase function more severely. Lysosomal dysfunction resulting in cell death, accumulated autophagosomes and lysosomes, reduced mTORC1 signaling and synaptic connectivity, and lowered neurotransmitter contents of synaptic vesicles are observed in the brains of Atp6v0a1A512P/A512P mice. These findings demonstrate the essential roles of ATP6V0A1/Atp6v0a1 in neuronal development in terms of integrity and connectivity of neurons in both humans and mice.

/pdf/atp6v0a1-encoding-the-a1-subunit-of-the-v0-domain-of-32ipqwe2bg.pdf

ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H + -ATPases is essential for brain development in humans and mice.

CaMKII and long-term potentiation (LTP) were discovered within a decade of each other and have been inextricably intertwined ever since. However, like many marriages, it has had its up and downs. Based on the unique biochemical properties of CaMKII, it was proposed as a memory molecule before any direct physiological linkage was made to LTP. This review will assess the state of this marriage 40 years on. How well does the physiological evidence support the role of CaMKII in synaptic memory and what are the remaining outstanding issues?

Synaptic memory and CaMKII: a review.

Blockade of adenosine A2A receptor alleviates cognitive dysfunction after chronic exposure to intermittent hypoxia in mice

https://doi.org/10.1016/j.isci.2023.106664

Neuronal SNAP-23 is critical for synaptic plasticity and spatial memory independently of NMDA receptor regulation

Improvement of synaptic plasticity by nanoparticles and the related mechanisms: Applications and prospects.

Recent evidence suggests that SNARE fusion machinery play critical roles in postsynaptic neurotransmitter receptor trafficking, which is essential for synaptic plasticity. However, the key SNAREs involved remain highly controversial; syntaxin-3 and syntaxin-4 are leading candidates for the syntaxin isoform underlying postsynaptic plasticity. In a previous study, we showed that pyramidal-neuron specific conditional knockout (cKO) of syntaxin-4 significantly reduces basal transmission, synaptic plasticity and impairs postsynaptic receptor trafficking. However, this does not exclude a role for syntaxin-3 in such processes. Here, we generated and analyzed syntaxin-3 cKO mice. Extracellular field recordings in hippocampal slices showed that syntaxin-3 cKO did not exhibit significant changes in CA1 basal neurotransmission or in paired-pulse ratios. Importantly, there were no observed differences during LTP in comparison to control mice. Syntaxin-3 cKO mice performed similarly as the controls in spatial and contextual learning tasks. Consistent with the minimal effects of syntaxin-3 cKO, syntaxin-3 mRNA level was very low in hippocampal and cortex pyramidal neurons, but strongly expressed in the corpus callosum and caudate axon fibers. Together, our data suggest that syntaxin-3 is dispensable for hippocampal basal neurotransmission and synaptic plasticity, and further supports the notion that syntaxin-4 is the major isoform mediating these processes.

/pdf/syntaxin-3-is-dispensable-for-basal-neurotransmission-and-2pngfvc9ez.pdf

Syntaxin-3 is dispensable for basal neurotransmission and synaptic plasticity in postsynaptic hippocampal CA1 neurons.

Voa protein is a subunit of V-ATPase proton pump which is essential to acidify intracellular organelles including synaptic vesicles. Voa1 is one of the four isoforms of Voa family with strong expression in neurons. Our present study was aimed to examine the role of Voa1 protein in mammalian brain neurons. To circumvent embryonic lethality, we generated conditional Voa1 knockout mice in which Voa1 was selectively deleted from forebrain pyramidal neurons. We performed experiments in the Voa1 knockout mice of ages 5-6 months to assess the persistent effects of Voa1 deletion. We found that the Voa1 knockout mice exhibited poor performance in the Morris water maze test compared to control mice. In addition, synaptic field potentials of the hippocampal CA1 region were greatly diminished in the Voa1 knockout mice when examined in brain slices in vitro. Furthermore, brain histological experiments showed severe degeneration of dorsal hippocampal CA1 neurons while CA3 neurons were largely preserved. The CA1 neurodegeneration was associated with general brain atrophy as overall hemispheric areas were reduced in the Voa1 cKO mice. Despite the CA1 degeneration and dysfunction, electroencephalographic recordings from the hippocampal CA3 area revealed aberrant spikes and non-convulsive discharges in the Voa1 knockout mice but not in control mice. These hippocampal spikes were suppressed by single intra-peritoneal injection of diazepam which is a benzodiazepine GABAA receptor enhancer. Together these results suggest that Voa1 related activities are essential for the survival of the targeted neurons in the dorsal hippocampal CA1 as well as other forebrain areas. We postulate that the Voa1 knockout mice may serve as a valuable model for further investigation of V-ATPase dysfunction related neuronal degeneration and functional abnormalities in forebrain areas particularly the hippocampus.

/pdf/observations-from-a-mouse-model-of-forebrain-voa1-knockout-1i3jm1z9h6.pdf

Observations From a Mouse Model of Forebrain Voa1 Knockout: Focus on Hippocampal Structure and Function.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Shan Shi

Author Tools

Chat about Author

Papers

Syntaxin-3 is dispensable for basal neurotransmission and synaptic plasticity in postsynaptic hippocampal CA1 neurons.

Observations From a Mouse Model of Forebrain Voa1 Knockout: Focus on Hippocampal Structure and Function.