|
Status |
Public on Dec 09, 2020 |
Title |
The genomic underpinnings of oscillatory biomarkers supporting successful memory encoding in humans |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
|
Summary |
Brain oscillations are remarkable components of brain activity that support memory encoding. However, it remains a major challenge to determine the molecular mechanisms underlining this activity in humans. Here, we used direct intracranial electroencephalography recordings from patients performing free recall tasks of verbal memory encoding in temporal cortex. Using resected tissue transcriptomics from the same patients, we linked gene expression with brain oscillations, identifying genes correlated with oscillatory signatures of memory formation across six frequency bands. Co-expression analysis isolated biomarker-specific modules associated with neuropsychiatric disorders as well as ion channel activity. Using single-nuclei transcriptomic data from resected tissue, we further revealed that biomarker-specific modules are enriched for both excitatory and inhibitory neurons. This unprecedented dataset of patient-specific brain oscillations coupled to genomics unlocks new insights into the genetic mechanisms that support memory encoding. By linking brain expression of these genes to oscillatory patterns, our data help overcome limitations of phenotypic methods to uncover genetic links to memory performance.
|
|
|
Overall design |
Transcriptomic data obtained from resected human Brodmann Area 38 tissue were integrated with intracranial electroencephalography (iEEG) data from the same subjects to link memory-related oscillations with gene expression in 16 subjects. Matched post-mortem tissues from healthy and epileptic individuals were used for cross-validations. Single-nuclei RNA-sequencing and single-nuclei chromatin accessibility obtained from similar Brodmann Area 38 samples were used to define the cell-type composition of genes and coexpressed gene expression modules associated with memory oscillation. Resected tissues were obtained from living donors.
|
|
|
Contributor(s) |
Berto S, Fontenot M, Ayhan F, Caglayan E, Douglas C, Konopka G |
Citation(s) |
33686299 |
Submission date |
Nov 04, 2019 |
Last update date |
Mar 10, 2021 |
Contact name |
Genevieve Konopka |
E-mail(s) |
gena@alum.mit.edu
|
Organization name |
UT Southwestern Medical Center
|
Department |
Neuroscience
|
Street address |
5323 Harry Hines Blvd.
|
City |
Dallas |
State/province |
TX |
ZIP/Postal code |
75390-9111 |
Country |
USA |
|
|
Platforms (2) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
Samples (56)
|
|
Relations |
BioProject |
PRJNA587524 |
SRA |
SRP228565 |