Gene-expression correlates of the oscillatory signatures supporting human episodic memory encoding

Abstract

In humans, brain oscillations support critical features of memory formation. However, understanding the molecular mechanisms underlying this activity remains a major challenge. We measured memory-sensitive oscillations using intracranial electroencephalography recordings from the temporal cortex of patients performing an episodic memory task. When these patients undergo resection subsequently, we employ transcriptomics on the temporal cortex to link gene expression with brain oscillations, identifying genes correlated with oscillatory signatures of memory formation across six frequency bands. A co-expression analysis isolated oscillatory signature-specific modules associated with neuropsychiatric disorders as well as ion channel activity, with highly correlated genes exhibiting strong connectivity within these modules. Using single-nuclei transcriptomics, we further revealed that these modules are enriched for specific classes of both excitatory and inhibitory neurons, and immunohistochemistry confirmed expression of highly correlated genes. This unprecedented dataset of patient-specific brain oscillations coupled to genomics unlocks new insights into the genetic mechanisms that support memory encoding.

FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells

“…The enrichment of pseudobulk differentially expressed genes and ASD-relevant genes was performed using the Fisher-exact test. Disease-relevant gene sets were used from a previous study (Berto et al, 2021). Fisher exact tests were performed in R with the following parameters: alternative = “greater”, conf.level = 0.85.…”

“…The enrichment of pseudobulk differentially expressed genes and ASD-relevant genes was performed using the Fisher-exact test. Disease-relevant gene sets were used from a previous study (Berto et al, 2021).…”

Neural oscillation coupling selectively predicts speech reception in young children with Autism Spectrum Disorder

“…As cortical oscillations arise from excitatory-inhibitory interactions within and across specific cortical laminae [121], auditory oscillation anomalies represent a plausible functional counterpart to structural disorganization and disruption of cortical inhibition previously shown in ASD [122]. A recent study directly relates neural oscillations with the expression of a number of genes, several of which are involved in ASD [123], e.g., LNX1, DGKI, KCNQ5, DCX, SHANK2, etc. Speech reception difficulties in ASD could, therefore, directly result from structural anomalies induced by mutations of genes [124][125][126] controlling neuronal interactions, notably at the synaptic level [125,127].…”

The gene expression signature of electrical stimulation in the human brain

“…Microglia are critical modulators of neuronal activity, acting to suppress excessive activity by inhibiting surrounding neurons, including excitatory neurons 21 . Researchers have correlated human brain transcriptomics with prior recorded oscillatory signatures of memory consolidation in human subjects 22, 23 , but this prior work did not identify changes in gene expression driven by activity and they did not observe microglial-specific changes. This identification of a microglial transcriptomic response following electrical stimulation presents an important conceptual advance in our understanding of activity-dependent gene expression in the human brain.…”