IMAGING HYPOTHALAMIC NEUROCIRCUIT AND DYSFUNCTION USING MEMRI

Abstract

HYPOTHALAMUS PLAYS A CENTRAL ROLE IN THE REGULATION OF ENERGY HOMEOSTASIS. MANGANESE-ENHANCED MRI (MEMRI) WAS PREVIOUSLY USED TO DETECT HYPOTHALAMIC RESPONSES TO VARIOUS HORMONES AND PEPTIDES IN VIVO. HOWEVER, IT REMAINS UNCERTAIN WHETHER CHANGES IN MEMRI SIGNAL REFLECT NEURONAL ACTIVITY, GIVEN THAT MEMRI SIGNAL IS DEPENDENT ON MN2+ UPTAKE AND TRANSPORT. HERE WE EVALUATED WHETHER MEMRI SIGNAL AND DYNAMICS IN DIFFERENT HYPOTHALAMIC NUCLEI REPRESENT NEURONAL ACTIVITY AND CONNECTIVITY TO THE ARCUATE NUCLEUS (ARC). WE PROVIDE EXPERIMENTAL EVIDENCE THAT MEMRI MAY BE USED FOR MAPPING ACTIVATED NEURONAL PATHWAY IN HYPOTHALAMUS IN VIVO, AND PROPOSE THAT MEMRI MAY FACILITATE UNDERSTANDING OF HYPOTHALAMIC DYSFUNCTION DURING OBESITY DEVELOPMENT. WE USE POMC/STAT3 KNOCKOUT (KO) MICE TO DETERMINE WHETHER MEMRI SIGNAL CAN DIFFERENTIATE NEURAL PATHWAY CHANGE BY SELECTIVELY SUPPRESSING POMC NEURAL PATHWAY. THIS STUDY WILL HELP TO EXPAND OUR UNDERSTANDING OF THE OVERALL PICTURE OF LEPTIN SIGNALING NEUR