Project description:Mechanisms governing how immune cells and their derived molecules impact homeostatic brain function are still poorly understood. Here, we elucidate neuronal mechanisms underlying T cell effects on synaptic function and episodic memory. Depletion of CD4 T cells led to memory deficits and impaired long-term potentiation. Severe combined immune-deficient mice exhibited amnesia, which was reversible by repopulation with T cells from wild-type but not from IL-4-knockout mice. Behaviors impacted by T cells were mediated via IL-4 receptors expressed on neurons. Exploration of snRNA-seq of neurons participating in memory processing provided insights into synaptic organization and plasticity-associated pathways regulated by immune cells. IL-4Rα knockout in inhibitory (but not in excitatory) neurons was sufficient to impair contextual fear memory, and snRNA-seq from these mice pointed to IL-4-driven regulation of synaptic function in promoting memory. These findings provide new insights into complex neuroimmune interactions at the transcriptional and functional levels in neurons under physiological conditions.
Project description: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.
Project description: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.
Project description: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.
