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Murray, K. T.

Publications and source records attributed to Murray, K. T..

2 recordsLinked to original sources

Learning to use landmarks for navigation amplifies their representation in retrosplenial cortex

Visual landmarks provide powerful reference signals for efficient navigation by altering the activity of spatially tuned neurons, such as place cells, head direction cells, and grid cells. To understand the neural mechanism by which landmarks exert such strong influence, it is necessary to identify how these visual features gain spatial meaning. In this study, we characterized visual landmark representations in mouse retrosplenial cortex (RSC) using chronic two-photon imaging of the same neuronal ensembles over the course of spatial learning. We found a pronounced increase in landmark-referenced activity in RSC neurons that, once established, remained stable across days. Changing behavioral context by uncoupling treadmill motion from visual feedback systematically altered neuronal responses associated with the coherence between visual scene flow speed and self-motion. To explore potential underlying mechanisms, we modeled how burst firing, mediated by supralinear somatodendritic interactions, could efficiently mediate context- and coherence-dependent integration of landmark information. Our results show that visual encoding shifts to landmark-referenced and context-dependent codes as these cues take on spatial meaning during learning.

neuroscience↗

Myeloid Cell-Derived IL1β Contributes to Pulmonary Vascular Remodeling in Heart Failure with Preserved Ejection Fraction

BackgroundPulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are not well understood. We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH in HFpEF, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF. MethodsEight week old male and female C57/BL6J mice were given either L-NAME and high fat diet (HFD) or control water/diet for 2,5, and 12 weeks. Bulk RNA sequencing and single cell RNA sequencing was performed to identify early and cell-specific pathways that might regulate pulmonary vascular remodeling in PH-HFpEF. Finally, clodronate liposome and IL1{beta} antibody treatments were utilized to deplete macrophages or IL1{beta}, respectively, to assess their impact on pulmonary vascular remodeling in HFpEF. ResultsMice given L-NAME/HFD developed PH, small vessel muscularization, and right heart dysfunction after 2 weeks of treatment. Inflammation-related gene ontologies were over-represented in bulk RNA sequencing analysis of whole lungs, with an increase in CD68+ cells in both murine and human PH-HFpEF lungs. Cytokine profiling of mouse lung and plasma showed an increase in IL1{beta}, which was confirmed in plasma from patients with HFpEF. Single cell sequencing of mouse lungs also showed an increase in M1-like, pro-inflammatory populations of Ccr2+ monocytes and macrophages, and transcript expression of IL1{beta} was primarily restricted to myeloid-type cells. Finally, clodronate liposome treatment prevented the development of PH in L-NAME/HFD treated mice, and IL1{beta} antibody treatment also attenuated PH in L-NAME/HFD treated mice. ConclusionsOur study demonstrated that a well-accepted model of HFpEF recapitulates features of pulmonary vascular remodeling commonly seen in patients with HFpEF, and we identified myeloid cell derived IL1{beta} as an important contributor to PH in HFpEF.

cell biology↗