GABAergic neuronal IL-4R mediates T cell effect on memory [Il4rkoT]

The immune and nervous systems are highly interactive, however, little is known about how immune cells and their derived molecules impact brain function. Here we show that T cells play a critical role in retrieval of contextual fear conditioning (CFC) memory. Single-nuclei sequencing (snRNAseq) of engram neurons and non-engram neurons from the dentate gyrus one day after CFC learning revealed new evidence about differential expression of immune-related and synaptic plasticity-related genes, in SCID vs. wild-type mice. These findings present a comprehensive picture on how T cells and their derived cytokines could regulate memory retrieval and provide new insights into the nature of neuroimmune interactions at the transcriptional level in neurons. Overall, restoration of T cells or IL-4R signaling might lead to selective rescue of memory retrieval, and proffer a valuable strategy for treating memory loss. Overall design: This experiment aims to compare the transcriptional profile of nuclei from 2 genotypes (SCID+T cell(WT)/SCID+T cell(IL4KO)) and 2 activation states (engram/nonengram). All nuclei were collected from the dentate gyrus of mice after fear conditioning. All mice were housed under standard conditions and injected with labelled viruses to detect the activation state.