Ketogenic diet dampens excitatory neurotransmission by shrinking synaptic vesicle pools

The ketogenic diet (KD) is a common dietary intervention for treating seizures in intractable childhood epilepsies and has been proposed to improve disease outcome in neurodegenerative disorders. Despite its clinical applications, we know little about how this diet impacts brain circuitry and neuronal function to elicit its protective effects. Here, we examined the impact of the KD on hippocampal function through integrative analysis of gene expression, epigenetics, and neurotransmission.  We found that KD induces profound transcriptional reprogramming of the hippocampus, including dampened expression of numerous synaptic genes. Through proteomic analysis of histone variants and post-translational modifications, we uncovered significant changes in activating and repressive histone marks in the hippocampus of KD mice. To determine how transcriptional rewiring of the hippocampus under KD impacts neurotransmission, we performed electrophysiological recordings of neurotransmission and ..., , # Ketogenic diet dampens excitatory neurotransmission by shrinking synaptic vesicle pools

Dataset DOI: [10.5061/dryad.rv15dv4m0](https://doi.org/10.5061/dryad.rv15dv4m0)

## Description of the data and file structure

C57bl6/NJ male mice were fed a ketogenic diet (KD) or chow diet (control). Total hippocampi were harvested for bulk RNA sequencing. Following RNA extraction, samples were prepared according to library kit manufacturer’s protocol, indexed, pooled, and sequenced on an Illumina NovaSeq 6000.  Basecalls and demultiplexing were performed with Illumina’s bcl2fastq software and a custom python demultiplexing program with a maximum of one mismatch in the indexing read.  RNA-seq reads were then aligned to the Ensembl release 101 primary assembly with STAR version 2.7.9a.  Gene counts were derived from the number of uniquely aligned unambiguous reads by Subread:featureCount version 2.0.3. Isoform expression of known Ensembl transcripts were quantified with Salmon version 1.5.2.  Se...,