Event Title
Confirming the Presence of Immune Memory Engrams in Mice
Abstract
It has recently been demonstrated that inflammatory responses in adults can generate specific neuronal ensembles whose reactivation recapitulates the inflammatory response. The goal of this project is to establish a reliable mouse model in which neurons active during an immune response can be tagged with temporal and spatial specificity. The project will then progress to reactivating those tagged neurons and observing whether their reactivation alone is sufficient to induce an immune response. To achieve this, transgenic TRAP (targeted recombination in active population) adult mice will be stereotactically injected with a DREADD-containing loxP-regulated AAV vector in the posterior insular cortex. A systemic inflammatory response will be induced by lipopolysaccharide (LPS) injection, during which time tamoxifen will be administered to allow for DREADD expression in active AAV-infected neurons. ELISA will be used to measure serum cytokine levels to confirm immune activation. For the second part of the project, mice that have recovered from their LPS-induce inflammation will have their tagged neurons chemogenetically reactivated by clozapine-N oxide (CNO) and the resulting immune response will be examined by ELISA. Based on the effectiveness of this model, it will be translated (with modifications) into embryonic mice. We aim to translate this into pregnant mice with the goal of creating immune memories in the fetus, as the ability of fetuses to form long-term memories remains unknown.
Presentation Type
Poster Presentation
Confirming the Presence of Immune Memory Engrams in Mice
It has recently been demonstrated that inflammatory responses in adults can generate specific neuronal ensembles whose reactivation recapitulates the inflammatory response. The goal of this project is to establish a reliable mouse model in which neurons active during an immune response can be tagged with temporal and spatial specificity. The project will then progress to reactivating those tagged neurons and observing whether their reactivation alone is sufficient to induce an immune response. To achieve this, transgenic TRAP (targeted recombination in active population) adult mice will be stereotactically injected with a DREADD-containing loxP-regulated AAV vector in the posterior insular cortex. A systemic inflammatory response will be induced by lipopolysaccharide (LPS) injection, during which time tamoxifen will be administered to allow for DREADD expression in active AAV-infected neurons. ELISA will be used to measure serum cytokine levels to confirm immune activation. For the second part of the project, mice that have recovered from their LPS-induce inflammation will have their tagged neurons chemogenetically reactivated by clozapine-N oxide (CNO) and the resulting immune response will be examined by ELISA. Based on the effectiveness of this model, it will be translated (with modifications) into embryonic mice. We aim to translate this into pregnant mice with the goal of creating immune memories in the fetus, as the ability of fetuses to form long-term memories remains unknown.